Catching Up – December 2020

Hi. It has been absolutely months since I wrote a page for this website. With COVID-19, my workload as a therapist has expanded. In addition to my day job, I was asked to do a side gig writing for a “health community.” Add to that my “doom scrolling” of online news outlets to check on the pandemic and election, and I have managed to let a few things slide.

As some of you know, Lin, my friend, editor, webmaster and purveyor of many good things, has had some serious health issues that are hopefully mostly behind her now. Her reasons for being m.i.a. from the website are much better than mine. [Lin/Linda here: thanks for the kind words, but we both have perfectly good reasons for not being here – they’re just different. ::smile::]

All by way of saying, sorry and making a pledge to do somewhat better. Not that we are going to present the quantity of material that we used to. Come the end of January, 2021, I will have been legally blind for FIVE years! How time flies when you are having “fun.” After that amount of time, I have adjusted. In some ways, being visually impaired has become old hat. I don’t have the angst I once had and my life is pretty routine. In other words, I can be really boring! And, yes, being visually impaired can be boring, too.

That does not mean, however, that everything is boring about my geographic atrophy. A few of you may know of my quest to some day regain my sight. Yep. Cockeyed optimist that I am, I have every intention of someday no longer being legally blind. The first step in my diabolical, master plan was to get into a clinical trial. That goal was reached about 18 months ago.

Since that time I have been going monthly for injections of a trial drug. The earlier results of the study suggested this drug, APL-2, slows down the rate of degeneration by about 30 to 40%. If things continue to progress at the rate they are now, it is not inconceivable that the first, clinically proven treatment for geographic atrophy will be on the market by 2022.

And it might not even be “my” drug that wins that race to be the first treatment for GA. The concept behind “my” drug – interfering with the complement cascade – is also the underlying concept behind other treatments in the pipeline. Those drug trials are doing very well also.

The second step of my diabolical plan was to get into a long term study that would hold me over until step three was ready. I am supposed to achieve inclusion in a long term study in the spring. The study is to determine how years of use of the drug affects my eyes. Will I develop side effects? Will the drug continue to work as well? Worse? Better?

I am willing and anxious to get into that study because it is a stepping stone to my next objective. That objective is a study that currently only exists in my feverish, little brain…and maybe the brains of a few researchers. That study will see how well transplanting RPE stem cells into eyes treated with the drug works.

After that? By that time I am speculating they will be ready to transplant photoreceptor cells and get them to connect to the optic nerve. Endgame. We see again. [Check out the Audacious Goals Initiative of the NIH NEI (National Institute of Health, National Eye Institute). That’s what they’re working toward.]

At least that is my diabolical plan. Step one will be completed and step two will start in the spring. I love it when a plan comes together.

If you are ready and able to join me and thousands of others as “lab rats”, if you are ready to become part of the solution, please volunteer for clinical trials research. Remember, this really is the best time in history to be going blind.

Written December 1st, 2020.

Retinal Repair Using Stem Cells: Part 1 – Background

Research into macular degeneration is aimed at:

stopping the disease from developing
treating it so that the disease process stops
reversing damage that has been done
curing it

I’ve shared many examples of each of these areas. You’ll find links at the end to 4 of my articles about research for wet AMD, for dry AMD, for gene therapy research, and for a cure.

In this article, we’ll look at what’s being done in clinical trials to reversing damage and to restore vision that has been lost.

Reversing Damage That Has Been Done

What about those who have an advanced form of macular degeneration and have suffered vision loss? This can occur in any form of macular degeneration including AMD, Stargardt’s Disease, and Myopic Macular Degeneration. The stem cell research applies to all of these.

Vision loss occurs when the photoreceptors die. These cells transmit signals to the brain which is where we get our sight. They convert ‘light to sight.’ They die because the cells that keep them alive called RPEs (Retinal Pigment Epithelium) falter and die. These RPE cells are critical to the retina’s ability to dispose of waste and to make sure the photoreceptors are nourished. We know that retinal cells don’t regenerate, so researchers have been asking the questions:

Can we keep the RPE cells healthy? Can we replace RPE cells that have died? If we do that, can we restore vision that is lost?

There is research into replacing photoreceptors, but it’s more difficult to do. It is currently being explored in the lab and with animals which is called pre-clinical research.

Restoring RPE Cells – Restoring Sight?

The answer to those questions about RPE cells have been found in the area of stem cell research. What are stem cells? They are specialized cells in our body that can make other types of cells. No other cells can do that. The stem cells used in research come from different sources. You can learn more about them in National Institute of Health’s Stem Cell Basics and A Closer Look at Stem Cells.

Here’s a very simplistic explanation as to why stem cells are of interest in retinal repair:

If they can make other types of cells, can they make RPE cells? The answer is yes! These new RPEs are called stem-cell-derived RPEs, and they’re created by the ‘magic’ of science (it’s complicated!) in the lab.
If we could take those stem-cell-induced RPEs and get them into the retina, could they replace failing or dead RPEs and keep the photoreceptors alive?

That’s exactly what researchers are working on.

Warning

The topic of using stem cells is one that has been discussed in MANY areas of healthcare. For retinal repair, there is NO proven safe and effective use of stem cells as a treatment for macular degeneration outside clinical trials which follow procedures that are rigorous and based on the scientific method. The first step is to establish the safety of the proposed treatment – that’s Phase 1. Only if the treatment is proven to be safe do the clinical trials progress to find the right dosage needed to be effective and to monitor any side effects. FDA approval comes at the end of a series of phases. You can learn more about clinical trials and why they are important by reading Treatments and Cures: Too Good to Be True? You can also find out what the FDA does and does not do related to macular degeneration.

Beware Unproven So-Called Treatments

Some people and clinics sell these unproven, not-FDA-approved stem cell treatments for macular degeneration. These costly procedures have blinded people & have not been effective for others. For more information about that, you can read FDA Warns About Stem Cell Therapies – Some patients may be vulnerable to stem cell treatments that are illegal and potentially harmful. The FDA has been working to shut down the sellers – that’s what they are – of these possibly dangerous procedures.

Unreliable Resource

The NIH National Library of Medicine has an online resource available called clinicaltrials.gov. It’s where researchers can list their studies which can be accessed by patients, their family members, health care professionals, and the public. Unfortunately, the site has no oversight, no vetting of the entries to make sure they are legitimate studies. Just because you find something that sounds interesting to you or someone you love, it doesn’t mean it is something to seriously pursue. You need to do much more research. I recommend the article Nine Things to Know About Stem Cell Treatments.

Stem Cell Research for Retinal Repair

The FDA approved their use for retinal repair in 2010. You can read about the early research in the 2018 article Stem Cell Treatment in Retinal Diseases: Recent Developments. Also, you can watch a great 2018 video Retinal repair: Bringing stem cells into focus.

The study of using stem cells is called regenerative medicine.

The Basics

Since retinal repair research started in 2010, the studies have varied primarily in two aspects:

1. The source of the stem cells. The options used so far are embryonic stem cells and induced pluripotent stem cells which are adult cells that are reprogrammed to look and act like embryonic stem cells. You can read about these in What Are Stem Cells and How Do They Work. The more recent research has moved to using the induced pluripotent stem cells for several reasons: use of embryonic stem cells has raised ethical issues, they are hard for researchers to get, have a higher risk of rejection, and they can migrate to other places with a possibility of creating tumor cells.
2. The method of transplanting the stem-cell derived RPEs. The purpose is to get these new cells in the area of the RPEs so they can be integrated with them. Initially, the cells were put into a suspension (a fluid) and injected into the retina. Unfortunately, those stem cells didn’t stay where they were placed. With the help of engineering experts, more recent research has put these cells on a monolayer (single layer) of a material to keep them together so that when they are implanted in the retina, they will stay in that area. The designs vary. Some other terms for this approach are patch, scaffold, layer, implant, or sheet.

Summary of the Concept

The basic way stem cell research is conducted is that ‘new’ RPE cells are created in the lab from stem cells and injected into the retina. Hopefully, these stem-cell-derived RPEs should then integrate with the person’s own RPE cells so that they can do what RPE cells do: nourish and clean up after photoreceptors. Sounds simple, yes? It isn’t. There are issues regarding rejection of these new cells and the safety of using immunosuppressive drugs, their possible migration to other places in the body where they may create tumors, safety of the method that delivers the stem-cell-derived RPEs, and more. That’s why the clinical trial process is so important!

The History

As I wrote above, the FDA approved the use of stem cells for retinal repair in research in 2010. Phase 1 clinical trials started that year. The purpose of phase 1 clinical trials is to make sure the treatments are safe. Since stem cell research for retinal repair was so new, researchers were very careful. These early studies used embryonic stem cells with their possible complications. One early trial was stopped out of concern for the participants.

Since then, many clinical trials have been done.

When doing your own research on this topic, make sure to check the dates of the resources since much has changed since 2010.

Two early Phase 1 studies were started in 2010 by Advanced Cell Technology (then called Ocata which became Ocata Therapeutics; it’s Astrellas currently). Professor Steven Schwartz, MD, and colleagues reported that 4 months after the first patients had the procedure they found no safety issues of tumor growth or rejection from using embryonic stem cells and no loss of vision. In 2015, they reported that of the 18 patients treated, more than half had improvements in visual acuity. They found evidence that the new RPE cells were integrated in the retina. They also reported that although the treatment was safe, which meets the objective of a phase 1 clinical trial, more follow-up was needed.

I could give you a LONG list of articles about the clinical trials that came after this one. A lot of progress was made, a lot was learned. I want to fast-forward to where we are today with this promising research.

Next: RETINAL REPAIR USING STEM CELLS: PART 2 – CURRENT STATUS 2020

More Research

A Cure in Our Lifetime?

Have Dry AMD and Wonder When There Will Be a Treatment?

Have Wet AMD and Hoping for Something Other Than Injections?

Gene Therapy Research for AMD. Stopping the Disease

Happy New Year 2020!

Hello and Happy New Year to you all!

It was February 12 , 2016 that I was given the news my second eye was “gone” as a result of dry age-related macular degeneration. It was that date that I was declared legally blind. You can do the math as well as I can so you know it is coming up on four years that I have been on my journey through sight loss. Hard to believe.

Time has passed rapidly. That is because Lin and I have been busy. Very busy! We started out with this blog. Journaling for my own mental health as well as the edification of others worked well.

It fact, for me, it worked so well I worked through my angst and became, well, shall we say, hard for the new folks to relate to. Consequently, I have been on semi-permanent hiatus here for a number of months.

What to say about that? How about this:

I hope for each of you to come to the point that I am at now. I hope for the pain and panic to end and for sight loss to become something that has enhanced your life almost as much as it has diminished it. Maybe even enhanced it more.

I believe Lin will agree my sight loss has enriched our lives quite a bit. While I did the “easy” work of going centrally blind, Lin rolled up her sleeves and got down to business. Her Facebook group is a minor phenomenon with several thousand members and a volunteer staff of assistants doing research and helping with the group in many ways. The Facebook group was the second thing that happened these past four years. It is something Lin is understandably proud of and I am proud of her. [Lin/Linda: Ah, shucks, thanks Sue!]

In the past six months or so, Lin and I started another endeavor. We were asked to write for Health Union. We saw – and see – this opportunity as a way to reach another audience of visually impaired people. Another way to help and support. Of course, I also saw it as a way to accomplish a secret ambition. I always wanted to be a paid author and now I am! Hot dignity dog!?

Another big accomplishment this year has been my acceptance into a clinical trial. Helping to advance medical science towards a treatment and eventually a cure for dry age-related macular degeneration through being in a trial became a goal early on in this journey. It is gratifying to have finally been chosen.

That brings me to another hope for the future. I hope that the time for newly diagnosed dry AMD patients being told there is no treatment and no cure is going to come to an end. Soon.

Where from here? The new year we are entering is 2020. It is the perfect year for a focus on vision and they are doing just that. While the initial thrust is on curing preventable vision loss, the definition of preventable is broadening every day. Regenerative medicine in the forms of stem cells and gene therapy will soon be a reality for many. New medications are slowing the progression of a number of eye diseases. This is our time, our fight, and it is exciting to be part of the endeavor.

Lin and I would like to thank you for enriching our lives over the past four years. When we started this journey, we had no idea things would turn out to be as gratifying as they have been. It has been you who have helped us turn my lemons into lemonade. You who have helped make so many good things possible. For this, we thank you.

Welcome to the year 2020 when exciting things will be happening. And remember, this is the best time in history to be going blind.

Written 12/28/2019

Next: Happy Anniversary – Celebrate the Successes!

Happy New Year 2019!

2019. Ready or not, it is here.

Not to make anyone feel old, but 2019 will be the 50th anniversary of Woodstock. (And October, 2020, Janis Joplin will have been dead 50 years. I still hear her on the radio almost weekly). 2019 is also the 50th anniversary of the first moon landing. How many of you could have predicted those things at the start of 1969?

Prognostication is a tricky business. Just ask meteorologists. (Which brings up another subject: does anyone else find 60 degree weather at Christmas to be scary? Lin/Linda: not if you live where it’s usually 60 degrees or higher at Christmas! ::grin::) However, with help – a lot of help! – from BrightFocus Foundation website (October, 2018), I will try to predict what we with Age-Related Macular Degeneration might have to look forward to in this new year.

Looking at the wet side of things first, now that they have proven treatments for neovascular, Age-Related Macular Degeneration, it is time to expand, refine and improve. New angiogenesis inhibitors – in other words, drugs that will retard the growth of extra blood vessels – are either on the market or will be coming soon. Some of the ones already on the market are Eyelea, Lucentis, Macugen, and Avastin.

In development are new, longer lasting anti-VEGF compounds. These things include Abicipar and Brolucizumab. Several of the ones currently on the market are also coming out in longer lasting formulas.

And let us not forget the new delivery systems in development. We reported on several different medication reservoirs that will allow patients to go two or three months without having to go in for a fill-up. Down the road, combination therapies, such as filling reservoirs with long acting medications, may allow people to go for shots every six to eight months if not longer.

Moving to the dry side of the street, things are starting to move on several fronts. My personal favorite is regenerative medicine, aka stem cell replacement/regrowth. We have spoken of the groundbreaking work being done with “the patch”. While I found nothing published about this since the spring, I cannot believe the research is not going on fast and furious. There are also studies being done in retinal pigment epithelial replacement by other companies. A search for Age-Related Macular Degeneration + stem cells yielded 34 hits on clinicaltrials.gov. Many of these are phase 1 studies. At least a few of them should progress to the next level.

Since there is a fair amount of evidence AMD has a lot to do with the function of the immune system, there are continuing efforts to intervene in the complement cascade. While lampalizumab fell short in phase 3 trials, APL-2 is entering phase 3 trials and looks promising. This medication is reported to intervene higher in the cascade process and is hoped to effect a wider range of patients.

And I haven’t even touched upon gene therapy or statin treatments or some of the most recent research in mitochondrial metabolism and AMD! All of these lines of study are showing some progress and may lead to finding a treatment and possibly even a cure.

Which study will break to the front of the pack? I have no clue. But one thing I do know is there will be progress made.

So back to Neil Armstrong from the Sea of Tranquility, 1969 “It is a great honor and privilege for us to be here representing not only the United States but men of peace of all nations, and with interest and the curiosity and with the vision for the future…”

May we, of all nations, patients and researchers alike, with interest, curiosity, and vision, continue to support one another in our quest for a cure for our shared nemesis, vision loss.

Happy 2019!

Written December 28th, 2018

Next: A MINOR EPIPHANY

Where’s Your Hope?

Hello, there! I have been trying to get some things done today….I gave up as of about 30 seconds ago. Nothing is happening.

Wait…that’s a lie. Our Facebook group just hit 1,700 members! Congratulations to Lin and everyone who has worked to make that group a success. [Lin/Linda here: as of my typing, there are at 1,738. The 38 were added this past week!]

And while congratulations are going out, we should also send one to my former retina specialist who I am ever hopeful will be my new research director, Carl Regillo. Dr. Regillo was named to the 100 most influential ophthalmologists in the world list. I find that pretty impressive.

And moving right along, researchers are expressing “cautious optimism” concerning regenerative medicine (read “stem cells”) treatments for AMD. Vavvas of Massachusetts Eye and Ear clarifies they are transplanting “differentiated cells…derived most often from iPS cells” that were themselves derived from stem cells.”

IPS cells are induced pluripotent stem cells. They can be induced directly from adult cells. These cells are “regressed” back to a state that will allow them to reproduce theoretically forever and also to develop into any one of every potential cells in the body. Perfect for “replacement parts”.

In other words, iPS cells avoid the ethical dilemmas that can be associated with embryonic stem cells.

Vavvas cautions it is still early days for regenerative medicine and all of the hype may be just that. Hype. Testimonials and anecdotal “evidence” are not scientific.

Massachusetts Eye and Ear is reported to be blazing new territory by combining regenerative medicine with neuroprotection approaches. The second of these approaches involves attempts to slow down cell death.

Vavvas goes on to once again caution against false hope.

The Cambridge English Dictionary defines false hope as putting your faith in something that might not be true. Fair enough. I would agree the crazy headlines after Coffey published were more than a little over the top. I would agree we have miles to go before we sleep, to paraphrase Robert Frost. I would contend, however, that something that might not be true still has the potential for being true. And that allows me to hold out hope for a regenerative medicine treatment if not a cure.

What it comes down to for me is, you have to have hope in something. Being told you have a condition for which there is no treatment and no cure is, well, disconcerting, to say the least.

So which basket do you put your eggs into? Which treatment are you betting on to actually do something substantive for us? Or have you decided there really is no hope?

To quote another great poet, Alfred Lord Tennyson, it is better to have loved and lost than to never to have loved at all. It just might be better to have false hope than have no hope.

Neal Burton in a 2017 Psychology Today article wrote that hope is an expression of confidence in life. It is the basis for virtues like patience, determination, and courage. Not bad. I can live with those outcomes.

So, yeah. I know we need to be cautious, but I still have hope. I still believe regenerative medicine is going to come through for us. Which potential treatment do you believe in?

Written August 15th, 2o18

Next: Coping: A Review

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The Waiting Game Continues

We’re off to see the Wizard! Not sure what this trip will accomplish except to tell me I am a bit blinder and to put me on the study referral list one more time. [Lin/Linda: Read about who the Wizard is in Sue’s page The Man Behind The Curtain: The Wizard of Wills.]

I heard from ‘my’ researcher at the beginning of the week. She said things were moving along and they were getting closer to launching the Astellas study. Not sure what that means. Does that mean six weeks? Six months? Six years? Also, while I interpret her responses as hopeful, she has yet to say I am in for sure. I chose to interpret everything she says as positive. [To read more about the Astrellas study, read Sue’s page The Waiting Game.]

“All that we are is a result of what we thought.” – The Buddha

Same day, afternoon

Well, we are back. Pretty much what I expected. A couple of new wrinkles. My disease is progressing at an average rate. The stem cell study should be ready to go sometime this fall. That will be about six months after the initial target date of March.

It appears people still have confidence in APL2. The slowing in the rate of lesion growth was promising, of course. The failure to slow vision loss along with that may be being seen by some as an experimental fluke. Apparently, they are expecting that will change when larger numbers are run. [To read more about the APL2 study, read Sue’s page The Waiting Game.]

Oh, and Regillo is pulling back to full-time in his Philadelphia offices, or at least leaving the satellite office I have been using. I am being given to an assistant wizard. Crap.

I am discouraged but not defeated. We are getting closer to the discovery of some sort of treatment for dry AMD. It is going to happen and I might as well help…not to mention being one of the first ones to get some substantive help with this thing. Really, you did not actually think I was being selfless; did you??

In the meantime, trying not to fall victim to a crappy mood, I have done a little self-help. I engaged in some behavioral activation and some good old DBT opposite to emotion. In other words I got moving and did something that would make me smile. A little positive activity is often helpful to quell a developing sour mood. That is especially true when there is nothing you can do about the situation.

Dancing on the deck of the Titanic? Yep, but remember, 706 people survived that disaster. That is nearly a third. Oh, and two dogs. (The stuff you can find on the internet!)

I have a friend who believes if you are not having success, you are not trying hard enough. When I tell her I will stay the course because right now Wills is “the only game in town”, she says I have to look farther afield! [Lin/Linda: not me!]

Alright, so Wills is number 2 in the nation. Shall we look at number 3? Wilmer at Johns-Hopkins is only 154 miles. That is realistic if they have something wonderful.

Out of 116 trials in Baltimore listed, only one was even vaguely appropriate. They are doing trials with Zimura. And guess what. Those trials are happening in Philly, too.

Take home message.? This is FRUSTRATING. Take care of yourself. No sense adding insult to injury. Getting depressed will not help. When people suggest you are not trying tell them you are linked in to an active network (that’s us!) and you are working to solve your problem.

To paraphrase the armed services, those who wait also serve. And sometimes that is the hardest job of all.

Written May 30th, 2018

Next: Combination Therapies

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How Can We Lose?

Hi! Hard to believe May is half over. One of these days I am going to wake up and be 90.

One of the 30ish girls in yoga declared she wants to live to be 110. Some of the slightly older folks said they wanted to live as long as they have quality of life.

What is quality of life? What is a life worth living (to put it in DBT speak)? That is something everyone has to answer for himself. However, whatever it is, we would like to think we are encouraging you to pursue it, vision loss or no.

I still don’t ‘get’ some of the reactions to my retiring from my school job. I was talking to my yogini about it the other day. She said what I say: I have been living my life for the past 64 years. (She has been living hers for 39). Why think I need to squeeze all of my ‘living’ into whatever time I have before my vision becomes even more of an impediment?

Maybe I have just been blessed what I have done for a living has contributed to my ‘living’. If you are/were not one of those people? Carpe diem, my dears. Carpe diem! Seize the day and get some living in!

Really not much happening here. I got two nights of lodging approved for the summer academy. That is the only way it will work since I will need to ride the bus down and back. Not liking that one but I am not being willful about it. Rejecting a slightly unpleasant solution – especially one that is the only solution! – is cutting off your nose to spite your face. [Lin/Linda: The summer academy that Sue refers to is the Penn State Summer Academy which is a program at the university that prepares high school students with visual impairment for college. You can read more about it starting with Sue’s page from last year I’m a Big Kid Now.]

But enough about me. Let’s talk about me! ?…no, not really. Let’s talk about the AMD information. VisionAware did an article in which they featured comments by Denis Jusufbegovic out at Indiana University. Dr. J. did a really nice job of outlining the clinical trial process and warning people – once again – to not get taken in on bogus trials. Remember, in the legit ones, they pay you, not the other way around. He also reminded us that these are experiments, not certainties. Don’t get taken in by people who promise you the world. Desperation is one thing. Vulnerability is another.

To end the article Jusufbegovic cited the research on CPBE-RPE 1. He gave that as an example of extremely promising developments.

What is CP…whatever? It is that experiment we talked about (webpage: The Patch) in which they used an extremely thin piece of Parylene to support a monolayer of stem cells for placement. The Parylene replaces the damaged Bruch’s membrane. Looking very promising.

The researchers for CPBE-RPE 1 are Humayun and Hinton. No only did they get $38 million to continue their research, Humayun was the 2015 winner of the National Medal of Technology and Innovation. This is the nation’s highest award for achievement in technology.

Humayun is no slouch. This Pakistani immigrant is the only ophthalmologist to be elected to both the National Academy of Medicine AND the National Academy of Engineering.

The best thing about Humayun? He is putting that brain power towards solving our problems! Can’t beat that with a stick. With people like Humayun in our corner, how can we lose?

Written May 20th, 2018

Next: Life’s Transitions

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The Patch

8:00 pm and I am rewarding myself. I just had a piece of chocolate and I am playing dance music on my iPad. This was the second day in a row I have felt as if I have actually accomplished something. Hallelujah. The to do list is starting to dwindle!

It won’t stay that way. Of course not. I know me. Besides, it is not good to become redundant. Meaning and purpose are like air. We need them to survive. Stay busy!

And on that note, I guess I should stop waxing philosophical and get to work here.

Lin sent me another article. As I alluded to on the last page, this one was about the development of a membrane to support the stem cell-derived RPEs. The research just keeps moving along!

It turns out this new development is coming out of Southern California. Specifically, the University of Southern California, the California Institute of Technology and the University of California at Santa Barbara.

Stop there a minute. University of California at Santa Barbara (UCSB)? Pete Coffey is at UCSB! The good Professor Coffey is co-director of their Molecular, Cellular, and Developmental Biology department. Gee, do you think there could be a connection? ? [Lin/Linda here: Professor Coffey is one of the researchers at Moorfields Eye Hospital in London who conducted the clinical trial that recently made the news with positive results of a similar trial conducted with 2 participants with wet AMD. He is also Director of the London Project to Cure Blindness. I found out that he splits his time 50-50 between University College London (UCL) and University of California Santa Barbara (UCSB). He isn’t directly involved in this study but does collaborate with the UCSB researchers.]

OK. Now it’s time to stop being a smart a** and tell you what they did; right? Right!

What they did was develop a “bioengineered implant consisting of stem cell-derived, mature, polarized retinal pigment epithelial cells in a single layer on an ultrathin synthetic parylene membrane”. Yikes. Let’s ‘unpack’ that as the saying goes.

Wikipedia gives an obscenely long and complicated explanation of bioengineering. You can look at it and figure it out if you wish. The definition in thefreedictionary.com was more simply “the application of engineering principles and technology to the field of biology, especially biomedicine, as in the development of prostheses, biomaterials, and medical devices and instruments.”

We have gone over stem cells quite extensively. We also mentioned that RPEs are polarized but I will go into that a little more deeply. In biology having polarity means the cell has distinct anterior and posterior parts. There is a ‘head’ and a ‘tail’. If they don’t line up right, they don’t work right.

Parylene is a polymer and is ‘green chemistry’. I refer you back to Wikipedia if you are interested in reading more. Social scientist here!

The purpose of putting the stem cell-derived RPEs on a membrane was to support them and and maintain their polarity. The patch was delivered to the back of the eye via the subretinal space (which we have talked about before) during an outpatient surgical procedure.

So how did they do? Apparently pretty well. Bear in mind it was only a phase 1/2a trial and there were only a few subjects, but the ‘patch’ seems to have integrated well and some of the people showed improvement in visual acuity.

For you on the west coast: they are enrolling subjects in six, different locations in California and Arizona. The clinical trial number is NCT02590692. If you are interested, get crackin’! Their numbers will be very small.

Next: Picturing AMD

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Different Paths

Good morning! I promised myself I would be productive today. Bedding stripped and in the washer, dishes in the dishwasher, a good pancake breakfast in my tummy, now if this webinar would load I might be able to DO something!

Speaking of pancakes, I was taught to flip the pancake when the bubbles are coming up in the middle. Visual cue. I burnt a couple today because I did not catch the little bubbles.

Short of singeing my nose on the griddle, how do I know when my pancake is ready to turn? Any low vision cooking suggestions? Inquiring minds want to know.

Moving right along, I happened upon a 2015 article in Drug Discovery and Development (DD&D) magazine. The article is a bit dated which actually goes to prove the point: research is advancing incredibly fast. Besides remarking that a Nobel laureate, Sir John Gurdon, called RPE replacement one of the most successful stem cell treatments in existence at that time, the article also talked about how regulatory agencies such as the Food and Drug Administration in the States and the Medicine and Health Care Products Regulatory Agency (MHRA) in the UK needed to get up to speed in the area of stem cells.

The article tells a cautionary tale about how the company Geron tried to get the first ES-cell clinical trial approved back in 1998. Their request and justification document ended up being 22,500 pages long and the approval came in – ready for this? – 2009! Good grief. The point is not that the FDA is an obstructionist organization. The point is stem cell science was an ostrich and they were used to dealing with elephants. Nothing fit their paradigms and they had no knowledge about it all.

Pete Coffey of the London Project to Cure Blindness told his own, mini horror story. He had two regulatory agencies to deal with. His wait was one year. Once again his ‘ostrich’ did not fit a system set up to deal with elephants. But kudos to the MHRA. They were not so hidebound that they could not adapt and modify.

The recent, controversial study published by Coffey, et al., was also discussed a bit in the DD&D article. After battling with the regulatory agencies and having his sponsor bail because of no fault of his own, Coffey expressed optimism that, essentially, the worst was over and his research would be moving on. In fact, there are rumors coming out of the UK that they may already be preparing for the next leg of this research. (Remember Lin has spies and secret agents everywhere.)

The article goes on to compare some of the different paths that stem cell treatment of AMD is following. Coffey used stem cells in people with wet AMD early in their disease progression. Work in the States is using stem cells in patients with geographic atrophy. In other words here we are treating after major damage has been done. Coffey and several others have started to be critical of the approach being taken in the US. Are we not at a point now we can pretty much trust the stem cell treatment? Must we wait until so late in disease progression? [Lin/Linda: click here for an article that talks about both the UK stem cell and the US stem cell trials results.]

The other comparison Coffey made was between simple injection of stem cells into the appropriate place and the use of a membrane to give structure to the cells. Coffey supports the latter approach….but that is the topic of an article Lin just sent me. Later!

Written April 7th, 2018

Next: The Patch

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Disappearing Fingerprints

I am back. Yes, we have snow. About three inches. Shirt sleeves and sandals back to ski jackets and mukluks in less than 18 hours.

I am trying to get back into the webinar. When I lose the connection it kicks me right back to the beginning of the session and I have to fight with the scroll bar again. Thinking it may be the friction ridges on my fingers. They are barely there.

This is a real tangential subject – and I promise to get back on topic soon – but many of us are ‘of a certain age’ and might be interested in this. The simple fact is, as we age, our fingerprints disappear. If you ever wanted a life of crime, now may be the time!

No, seriously. They disappear. A few years back I had to renew my clearances and I had to go back to be fingerprinted at least three times. We finally just gave up and declared me safe to work with kids. It was crazy frustrating.

Another Aging Puzzle: The Case of the Disappearing Fingerprints has all sorts of neat info on this topic. You might want to look at it. Especially if you need to be fingerprinted for volunteer work or something. Get you prepared for having to go back and back and….

Back on subject: the article on nine things to think about when considering a stem cell trial. I am still looking at the bullets under the first point so this review might take a while.

Expense was another thing to consider that they mentioned. The last I looked the pay for the trial I want was $75 a day. Holiday Inn Express was giving discounts on rooms if you needed to stay. So basically, we might be able to stay for ‘free’ but meals, gas and wear and tear are going to be all ours.

Knew that. Actually, it is part of the reason I am retiring. Retired I have a pension, a guaranteed income even if I need to spend days in Philly. If you are still working and looking at clinical trials of any type, you will need to consider the possibility of lost wages. Nasty thought but it may need to happen.

Oh, and we have said this before but it is worth repeating:

We do NOT pay to be in stem cell trials or to get any other experimental treatment.

If some ‘doctor’ says he has a great, experimental treatment but you need to pay? Get out of there as quickly and graciously as possible and call your local medical ethics board. There is something wrong and it needs to be looked into.

Second bullet is covered. Yes, we know there are different types of stem cells. There is a whole bunch of science involved here but they have done all these manipulations to be sure the stem cells in my chosen trial are appropriate.

The caveat here is know your provider. Wills Eye Hospital has been ranked the second best in the nation. (What’s first? Bascom-Palmer in Miami.)

Carl Regillo, my retinologist, has credits as long as your leg. Open a page covering an ophthalmology convention and the boy’s picture is there. Too legit to quit…or to do shoddy research.

OK. That covers points 1 and 2. Bye!

Written April 2nd, 2018 Continue reading “Disappearing Fingerprints”

Dissemination of Ideas and Facts

I am distracting myself. Still fighting with the webinar. If I don’t step away the laptop is flying into the yard and it is not mine.

Looking at the next point in that article, I noticed they have “embryonic stem cells” in italics. Perhaps a subtle way to make people raise their eyebrows?

I double checked the source of the article after seeing that. It is the International Society for Stem Cell Research. Their purpose is to promote and foster the dissemination of ideas about stem cells.

Promote and foster the dissemination of ideas. Facts, too. Sounds like a plan.

I am aware there are folks reading this who are totally opposed to stem cell research. No problem. That is your prerogative. Depending upon religious views about such things as when does life start, etc., people may decide it is an immoral practice. I just want to put some facts out there for the people who may be making their decisions on half or incorrect information.

Scientific American in Getting It Right About Stem Cells quoted at that time (2010) there were 800 stem cell lines worldwide. A stem cell line is a family of constantly dividing cells produced from a group of parent cells harvested from a single embryo.

Now stop there for a minute. Embryo here does not mean a well delineated little person. Embryo in this case is a blastocyst four to five days after fertilization. According to Medicinenet.com a blastocyst is a thin-walled, hollow structure made up of two layers, the inner and the outer layers. Conception: How It Works tells us a fertilized egg does not attach until at least five to six days after fertilization. Conception also tells us 50% of all fertilized eggs are lost before the woman’s next cycle.

Next question: where do the blastocysts come from? According to Getting It Right again as of 2010 there were 400,000 fertilized eggs (blastocysts) in storage in the United States alone. The New York Times estimated that number had grown to 612,000 by 2011. By 2015 when the article was written? Estimates were around 1 million.

What to do with all those blastocysts? Implant them? The reason they are still in storage years later is often because the original donors (or parents if you prefer) have successfully delivered several children and want and can handle no more.

Give them away? To whom? There are tons of problems there.

Keep them in storage at the fertility clinic? The Times reported storage costs of up to $1200 a year. What if you cannot afford that? And what happens when you age and die?

That leaves destruction or donation to science. How many fertilized eggs are destroyed every year? I could not find a number for the States but the Telegraph claimed in 2012 there were 1.7 million fertilized eggs “thrown away” in the United Kingdom.

One more point before I sign off. Wikipedia reported in 2017 there were 378 approved stem cell lines in this country. However, only a handful of these lines are actually being used. The National Stem Cell Bank reported 77% of the requests they received were for only two of the lines they control.

And I lied, one more point. How long can a stem cell line last and be productive? We don’t know but some people have hypothesized they could be ‘immortal’.

There is precedence for that. Cancer cells taken from a woman in Baltimore in 1951 are still alive, multiplying and being used in research. Don’t believe me? Her name was Henrietta Lacks and the story is interesting. Look her up.

There you go. Change you mind? No? Your prerogative. I just wanted to share a few facts.

Written April 2nd, 2018 Continue reading “Dissemination of Ideas and Facts”

Behold the Turtle

Two days down on a three-day weekend. I am doing reasonably well with my ‘to do’ list. Progress through those is a good thing. It makes me feel a bit more accomplished.

I sent an Easter greeting to the researchers who will be conducting the clinical trial I have been trying to get into. The answer I got was the trial that was slated to launch in March (never believe those predictions!) is now in startup phase and should be ready this Summer. Maybe.

Of course, I was hoping – still AM hoping! – to be a first draft pick lab rat and for the research to actually begin this Summer. It will work out better for my schedule.

Not that the world revolves around moi…although it would make things a lot easier. You know what I am saying?

Of course, the treatment I have been wishin’ and’ hopin’ and thinkin’ and prayin’ (with apologies to Dionne Warwick way back in 1958) for is a stem cell treatment. Regenerative medicine. Therefore it was with interest that I read the article Nine Things You Should Know About Stem Cells that was shared in the Facebook group.

The article says there are complications that may occur with any treatment. The trial I am signed up for involves a vitrectomy. Vitrectomies almost inevitably lead to cataracts. The stem cells themselves may trigger an innate, immune response that could cause more damage. Then there is the possibility the stem cells could be contaminated and cause infection. Or they might migrate and cause a growth. There are dozens of potential SNAFUs. Most of us are old enough and wise enough to know there is no such thing as a sure thing.

If clinical trials were sure things they would not be called experiments. They would be called certainties. Who said “Behold the turtle. He only makes progress when he sticks his neck out”? (Found it. James Bryant Conant). Sometimes you have got to stick your neck out. You do it with thought. You do it with your eyes wide open but you do it.

Doing this trial will automatically make me ineligible for any other trials. That is just the way it works. It is important the researchers know the results they got are a result of THEIR treatment. Not the result of a treatment you had somewhere else.

It is for that reason you chose a clinical trial with a treatment you have researched and believe in. We have a Facebook group member whom Lin told me was offered a trial with a treatment he was not sold on. He turned it down. You get one trial. You get one shot at this. Pick something you know about and believe in. [Lin/Linda: you can read about Facebook group member Bob O’Connell’s decision making process on page 2 of his Guest Author’s pages]

Those were just two points under the first of the nine reasons; believe it or not. I will look at the rest and may just write a follow-up page. Maybe not. Right now, it is bedtime for this ‘turtle’. Catch ya later!

Written April 1st, 2018 Continue reading “Behold the Turtle”

Another Cautionary Tale

Watching a ‘circus act’ out on the deck. The pups are now able to hit the top of the picnic table from a stand. Yesterday they got a bunch of bananas off the counter. Fought over them and rolled on them. On the living room rug. If nothing else they get points for unique and creative.

As with everything, the pups’ exploits bring mixed reactions. Some of you are laughing. Others are appalled.

The ‘big news’ of the week is making a lot of people pretty excited and happy. I imagine you heard Pete Coffey, of the London Project and University of California – Santa Barbara, is saying he will make stem cell treatments readily available to all comers in five years. He is reporting utterly amazing results for a phase 1 stem cell experiment. [Lin/Linda here: to see the list of articles from various sources, click here.]

Whoa! Hold on for a minute! Unfortunate I must take the loyal opposition stance on this one! I am – to understate things – a tad skeptical. There are problems here.

Lin has her ways of getting things. She has a pretty good network of spies and other secret agents. One of her spies shared the published article with us. I have not read it all yet, as a matter of fact, I have barely started it – things are just not calming down around here – but some stuff I did see made me concerned.

Let us start with the timelines they lay out. This research was done in the summer of 2015 but we are just hearing about it now. Where have they been for the past two and a half years?!?!?! If this stuff is so hot, they should have been shouting it from the rooftops a lot earlier than now.

Even more suspicious? The submission date for publication was November, 2016 but the acceptance date was February, 2018! Anyone who has written a thesis or a dissertation knows what that year and a half lapse represents: a whole pot load of rewrites! What was wrong with the original work? Inquiring minds and all that.

There are other things that are wrong, wrong, wrong. Now, I applaud Douglas and the second person who wishes to remain anonymous. I really do and I will come back to why in a second. But seriously, how often can you be on a first name basis with half of a subject pool? There were two people in this study! The FDA suggests 20 to 100 people is the appropriate number of subjects for a phase 1 study. What happened to the other 18 people? This study sounds likes it is providing more anecdotal information than research findings.

And why do I applaud Douglas and the other person? They had enough guts to participate in phase 1 research. Phase 1 research is safety and tolerability, folks. They are looking for weird reactions like growing hair out of your eyeballs or having your head spin around. ( OK, so I am a little fanciful. You still get the idea.) This is not the proof of concept phase.

The Food and Drug Administration (FDA) gives an estimate of six to eleven years to get a medication or treatment through phases 1, 2 and 3. Coffey is saying he will have his treatment on the proverbial shelves in five years. Now granted, he is talking about availability in the United Kingdom, but I assume they also have a cautious regulatory agency working there. How does this get shelf ready in five years?

And these are just questions I have off the top of my head!

My emotional self would love to believe this is happening. My rational self is very skeptical. My advice would be to stay hopeful but also remain skeptical. Like puppies mashing bananas into my carpet, this study may create some positive emotions but I think there is still something wrong with the picture.

Lin/Linda here: I’ve created a page with some other concerns that we have: Considerations in Evaluating Recent Stem Cell Clinical Trial in the UK

Written March 19th, 2018

Next: Furious and Proud

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Considerations in Evaluating Recent Stem Cell Clinical Trial in the UK

I hope that you know that I am NOT trying to say that the results of this study are not valid or not hopeful. Not at all! It’s a great first step but Sue and I and others believe that this treatment won’t be available in 5 years as is being claimed. There is still too much yet to do.

Here are some considerations that we’ve found:

1. This is not a ‘cure’, the person’s vision was not restored to the before-AMD state and this will not help everyone. If a person’s photoreceptors have been damaged, inserting RPEs will not restore vision which is what the photoreceptors do. RPE cells ‘help’ the photoreceptors function. This is for those people who have some functional photoreceptors with RPEs that can be restored or rejuvenated.

2. The scientific article was received by the Nature Biotechnology publishers on November 6th, 2016 (yes, 2016!), accepted on February 28th 2018, and published online March 19th, 2018. This journal is peer-reviewed so it’s highly likely that the delay was because they had questions, asked the authors to explain what they did and how they did something.

3. There were 10 people enrolled and only 2 people got the treatment (stem cells). They can say they have 100% success but what about the others? I read that they said they would be treating another participant but no mention of timeline. Just this morning I saw a video that said that 8 more patients will undergo the procedure but there’s no timeline.

4. The Pfizer company was the sole funding source when the clinical trial started. When 2 of the 10 participants were enrolled, Pfizer suspended funding for ‘strategic commercial reasons’ not related to the trial. We are not sure where the funding will be coming for future research.

5. This is a really early phase of clinical trials. Phase I is the first of the phases. Its purpose is to make sure they’ve got the proper dose and to see if there is any ‘hint’ that it works. Phase II is the preliminary safety, final dose finding and looking at the results according to ‘endpoints’ they set at the start. Phase III is where they really prove if it worked and to make sure it is safe.

6. Before this can be used on the public, it will have to pass through regulators. Consider the phase & this aspect, it’s hard to believe that it could be available in 5 years.

7. They’ve only observed these 2 people for 12 months. They will be followed for 5 years. One thing that can happen with stem cells is that they can migrate to other locations and grow tumors or they can be rejected.. That’s why they give immunosuppresant drugs after surgery. It this case it was prednisone delivered directly to the eye. There’s no information about the long-term use of it. The woman who was treated is diabetic and the prednisone caused a change in her blood sugar (they were able to adjust it).

8. The purpose is to insert a ‘patch’ of RPEs generated from stem cells. It won’t replace all RPEs. It definitely won’t replace photoreceptors that give us sight.

9. There is no sham surgery done so you can’t 100% say that it was the stem cells that improved their vision. Sham surgery would be the researchers using the surgical technique exactly as the treatment technique but without the RPEs.

Yes, we will follow this and report anything we find to you.

Written 3/23/2018

Optimistic for 2018

TGIF. Thank God it’s Friday! Not that the weekend is going to give me much reprieve. I have exercise classes on Saturday and a party on Sunday not to mention puppy parenthood, housework and several reports to write.

There is no rest for the wicked. Not that I have been exactly lax. This just seems to be a life with a lot to do…and I like it. I like it!

Nice to see in Newsweek and the Daily Mail that being busy and stubborn lead to longevity. Those of us with a strong work ethic, pure cussiness and a need to be in charge seem to take the years a little more easily.

There is certainly going to be a lot to do this year. In 2018 I turn 65 and need to navigate Medicare and some sort of other insurance for my cradle-robbed husband. My calculations indicate I am losing over $6,000 a year by still working at the school. My pension would pay a lot more. That and my ever failing eyesight suggest retirement from there and working full-time at the psychology practice may be the way to go. I still have some things to check out so we will see. Keep you posted.

We have a big project coming up at the office. We get to be involved in a statewide training for DBT this Spring. I have several ideas about what I want to do with that. I have discovered I really like to teach and I believe DBT is needed by our younger folks. I would love to introduce DBT in the schools.

Like I said, lots to do and I am optimistic about my opportunities. And that includes my opportunities for my vision.

Did you see Luxterna gene therapy is now on the market? Luxterna is $850,000 for a treatment! That is a hell of a lot of bake sales but I would expect many if not most communities would work to buy vision for some little guy or girl.

Remember Luxerna works by modifying the gene RPE65. RPE65 ‘recharges’ chemicals in the retinal pigment epithelial cells so they can still participate in the visual cycle. If they can reprogram RPEs to do that, how much longer before they can modify them for our diseases?

I have it on pretty good authority the APL-2 studies launch again this calendar year. That’s exciting. What is also exciting is I believe the Astellas Pharma stem cell trials will get going this year as well.

Progress is being made. Lin shared a recent article on how they are increasing the success rate for transplanted RPE stem cells. Optimally RPE cells are to line up and form a single, functional layer of cells only one cell thick. This is everyone nose to tail, all facing in the same direction.

In order to do this the RPEs have to have well-developed primary cilia on them. Primary cilia are little, hairlike things that generally serve as the sense organs of the cell. Lab grown stem cells often don’t have the best cilia on them. When they line up, things can get a little wonky.

Kapil Bharti and the folks at the National Institute of Health have discovered a drug that helps RPE cells grow beautiful cilia. Beautiful cilia cause the RPEs to line up in pretty lines and the results of the transplant are more successful. Ta da!

So, optimistic about 2018? Oh, yeah. You just gotta believe. Every small step is progress. Once again: this is the best time in history to be going blind.

Best wishes for 2018.

Written January 5, 2018 Continue reading “Optimistic for 2018”

My New Career?

Not to belabor a point, but today did start as a rather poopy day. We had our first snow overnight. Just a couple of inches but it was the puppygirls’ first snow. My theory is this: when they went out and squatted to poop, they got cold, wet bottoms. Go inside and poop? No cold, wet bottom. Problem solved!

Of course, since my husband was first on scene and got to clean it up, he was NOT a happy camper. Not a good start to the day.

Then there was the snow itself. Getting to my eye appointment is a 90 mile trip one way. My husband does not like city driving and he does not like driving in the snow. Once more he was not a happy camper.

It is hard to explain to some people why we have been dutifully driving 90 miles one way, every six months just to be told my eyes are worse. “Please pay your copay.” For those kind of results, I could go five miles down the road!

However, it is all part of a master plan. I have real problems with defeat. Real problem being told there is no answer. If you cannot supply me with an answer, I will find someone who can!

So here I am, running to see Regillo every six months for the past two years….and I think I am getting closer!

First the good news/bad news. Or, in this case, bad news/good news. Although I find it hard to believe, I have fallen down below 20/400 acuity. Bizarre because I don’t feel blind and don’t think I function as a blind woman.. After all, I got the “you don’t look blind!” routine just last month.

However, the good news on that is my vision is now so bad, I can satisfy the truly awful vision requirement for the Astellas’ study that is supposed to launch in March! Regillo referred me again. Is this time four or time five? I have sincerely lost count. [Lin/Linda: I put the details to that study in Sue’s page The Waiting Game.]

He has also put me on the list for APL-2 which is supposed to go into phase 3 clinicals sometime in 2018. He started to offer me “something else” when we were talking about lamp stuff (which is apparently very dead in the water) and I surprised him by knowing exactly where he was going. Working on being memorable. I want my name at the top of the list. [Lin/Linda: Sue wrote about APL-2 in her page My Friend in Manila?]

Also thinking I may be getting closer because I got a new test today. They ran me on the autofluorescence test. This test uses a very bright light. When the image is examined, the areas of the macula that are already dead are black and the areas that are in distress shine. My eye probably lit up like a Christmas tree. If that gets me into a study and gets this stuff stopped? Good.

So, that is where we are. I got a new test. I chose to be hopeful it means they want more information for my new career as a lab rat! Regillo generally seemed positive. Maybe I will be going to Philadelphia.

Written Dec. 14th, 2017 Continue reading “My New Career?”

Progress Daily

I really cannot win with this transportation business. Now they are on a string of late pick-ups and I am waltzing in 45 minutes after everyone else. Grrrrrrrrrr!

Oh well, can’t fix it. Time to start a page…..and as soon as I am into it, they will show up. Same concept as going to the bathroom in the restaurant to ‘make’ your meal arrive faster. Aha! Recognition! You have done that, too!

PRELUDE, the study, is NCT02659098. I checked and this is the same study I put my name in for last year. I just shot off a message to my research contact and asked her to make sure my ‘registration’ is still good. I am nothing if I am not persistent. Sad to say it is one of my better traits (oh no!)

There are actually two, main measurable outcomes they are interested in. There are the efficacy of the delivery system and best corrected acuity after administration of the stem cells. In the clinicaltrials.gov post they refer to the stem cells as CNTO 2476. In other literature they named the stem cells Palucorcel. I guess it is better than George (with apologies to the royal family. I have never liked the name George, although the little guy is a cutie!) Of course, Palucorcel does not exactly fall trippingly off the tongue.

Anyway, according to a one page write-up by Jessica Lynch, previous attempts to circumvent the vitreous and go in subretinally caused too many problems. They are, as I had been led to believe previously, trying to go around to the macula using the suprachoroidal space as their passage. (Anyone ever see Fantastic Voyage? I keep thinking how incredible it would be to jump in my microscopic submarine and motor through the suprachoroidal space!) After preclinical trials with mini pigs were successful, they launched into prime time with a phase 1 trial with people. As I said, they are now recruiting for phase 2. [Sue wrote about subretinal and suprachoroidal are in the previous page: Secret Passages in the Eyeball

Looking at the additional data on clinical trials.gov I discovered there are secondary outcomes for the study. They will be looking at quality of life and reading speed as well as whether the stem cell transplants slow or even stop the growth of the geographic atrophy. They are also looking at how many people convert to wet AMD. It sounds as if this study would be a long term commitment for the ‘lab rats’ chosen.

Going back to the Medscape article about phase 1, I discovered they had pretty good success threading through the space and the transplanted cells grew and started to function.

Cell placement was important. They used the microperimetry to figure out what retinal areas the subjects were using for eccentric viewing. Too close and that could be messed up. Cell placement other places was better.

Results? The subjects had some improvement in vision. That was SOME. Before you get too excited, remember this is RPE replacement. RPEs do not see. They support your photoreceptors. Some of the photoreceptors that are at death’s door may come back but the dead ones stay dead.

I did run off the journal write-up on phase 1 and I promise to tackle it and see if there were any other cool findings. Later. Right now I have laundry to sort. Maybe listen to an NCIS episode. It is now playing all the way through on my tablet! What can I say? It really is the little things.

Progress daily, guys. Progress daily. We will get there.

written October 17th, 2017 Continue reading “Progress Daily”

Secret Passages in the Eyeball

Back again. Chatty sort, ain’t I? ? I really thought I was done for awhile but I keep finding things; ya know? If (should I even use the word ‘if’?) you are tired of hearing me chatter, please write a page! We are anxious for more offerings. [Lin/Linda: if you haven’t read the pages by our guest authors, click here to see what we are talking about.]

Back to the topic at hand (I am not only chatty, but I go off on tangents, a lot of tangents??☝ ) the most recent thing to land in my inbox is a Medscape article Lin sent me. We are back to the stem cell research!

This article uses a lot of the concepts and vocabulary we have introduced over the months. I will review as we go along – I don’t remember it all myself! – and Lin might help us out with some links to previous pages. Pretty please and thank you. [I think the best place to learn about stem cells is a short YouTube video. Also, check out Sue’s early page Research.]

I am signed up for a Janssen Pharmaceutical study with stem cells. Guess who did this study? Do you ever feel LEFT OUT? Once again, I would love to know how to get on the A list for these things. Not sure all the places the study happened, though. One place was Kentucky. Maybe I was a ‘geographic undesirable’? I will have to do a little research after hip hop. (Some things do take precedence!?)

OK. Here we go. I looked up PRELUDE, etc and got routed to Clinical trials.gov. It is only going into phase 2 but the good news is they are recruiting. The better news is they are recruiting at Mid Atlantic Retina, Regillo’s place. Now I am getting stoked. “Watson!…The game is afoot!”

Shoot off an email later and get ready to accost Regillo when I see him in December. One other person who is only starting to realize the depths of my tenacity! (Cue Vincent Price laughter!)

OK. Enough nonsense….for now?. From the looks of things, PRELUDE was a study checking, for at least one thing, the feasibility of a delivery system. If you recall, we talked about ways of delivering stem cells to the back of the eye where they belong before. No just shooting them into the vitreous fluid where they roll around like loose cannon balls and end up who knows where. No, no, no! They must be placed. The way they are placed is to thread them through the subretinal space.

Now I am thinking the suprachoroidal space and the subretinal space are the same thing but I really don’t know. [The title of the article I linked to above is “Subretinal Delivery of Cells via the Suprachoroidal Space: Janssen Trial”.] How many ‘secret passages’ can an eyeball have? Be that as it may, the whole idea is to snake through this space (or spaces?) and get to the back of the eyeball without violating the integrity of the vitreous and opening it to infection.

The progress of the implanted cells in this study was checked with microperimetry. This appears to be an up and coming imagining technique we also talked about. It is a technique that tests which parts of the retina are working and how well they are actually working.

Which brings me to my word limit and bedtime. I have been to hip hop and back and need to take a bath and get ready for bed.

I did find what I think is the original journal article for this as well as the clinicaltrials.gov listing. I will follow up….tomorrow.

written October 16th, 2017 Continue reading “Secret Passages in the Eyeball”

Reading Modern Retina

Never thought I would be skimming back issues of Modern Retina, but here I am! Let us get back to some of the science stuff.

Amyloid beta is a major component of plague found in the brains of those with Alzheimer’s. There has been some suspicion AMD and Alzheimer’s are related at a genetic level. A recent study completed by Cheryl Guttman Krader failed to show any positive effects of injecting an antibody that targets amyloid beta into the eyes of those of us with geographic atrophy.

For the time being this means this line of inquiry will be abandoned or re-worked. Proof of concept did not occur and these researchers might go on to investigate something else.

Why are negative findings good news? One less blind alley to investigate! Since we don’t know which ideas may bear fruit, they all have to be investigated. Eventually we get to only the ones that have the most promise. Scientific method.

And another reason I think this finding is good news? It sort of suggests the Alzheimer’s and AMD connection may not be so cut and dry. Phew!

Here is another failure in proof of concept. Aflibercept is called Eylea when it is used as an inhibitor of vascular endothelial growth factor (VEGF – read “one of the things that makes the extra veins grow in AMD”). Michelle Dalton tried implanting stem cells in the eyes of patients who had been getting Aflibercept. She hoped the stem cell would produce the natural vascular endothelial growth factor and make the shots unneeded.

Unfortunately, many more patients than she had hoped required rescue doses of the drug. However, she also had people who kept the stem cells alive and these imported new stem cells did produce some of the Anti-VEGF molecule. Quantities were just too far below a therapeutic dose.

While this may be a failed experiment on the face of things, it is not all bad. Knowing there was some production of the desired molecules means this procedure may be very helpful once they figure out why it worked the little bit it did. Magnifying that effect may lead to fewer injections.

Last one, David S. Boyer wrote a review on multiple strategies being investigated for treating dry AMD. While many protective strategies for our photoreceptors and RPEs have failed, one they are still looking at with interest is brimonidine, brand name Allergen. Allergen is once again an intravitreally administered drug. (That is needle in the eye. We appear to be destined to join our wet AMD friends in that fate!) Coming out of phase 1 trials, brimonidine looks good. Next for it is phase 2, proof of concept. Will it perform as hoped?

Glatiramer acetate is looking good for reducing drusen. Glatiramer is used to treat multiple sclerosis, a disease in which the immune system wears away at the covering on the nerves. The theory is that glatiramer acts as a decoy to mitigate the autoimmune reaction. This treatment is based on the idea AMD really is an autoimmune disease.

There has been some evidence glatiramer reduces drusen, but Dr. Boyer warned us drusen can become fewer on their own. Drusen regression.

And that is a topic for another page.

written June 26th, 2017

Continue reading “Reading Modern Retina”

BIG News!

Woke up with a start at 2 am last night. Probably several things.

First thing that happened was a call from one of my contracts. She had called my third place of employment to schedule an evaluation and was told I did not work there anymore!

News to me! Now, I don’t get there a lot but the plan was for me to go and do a case or two when called. Maybe something like once every six weeks or so. I was never told I was being fired!

Of course it turns out someone got something wrong but it did get me to thinking. Once again, how does one graciously bow out or – hopefully equally graciously – be shown the door? Inquiring minds.

The second thing that has me a little anxious is my big ‘field trip’ tomorrow. I am going to do some sightseeing on Manhattan with an acquaintance from school. First time that far away from home without my husband since my sight loss. I know it can be done, but it is still a little scary.

Third thing: I saw Regillo yesterday. My eyes are getting worse slowly. (I am not so sure about the slowly part!) He confirmed scotomata (aka blind spots) get darker but did not necessarily say they go black. He said that he would not expect a central vision loss to cover 60 degrees of arc. That wide a loss would be ‘extreme’. Those two answers at least get us slightly closer to settling two of my burning questions from this Spring.

The big news, though, is he wants to try me on lampalizumab next winter. It appears the phase 3 clinicals are going to wind down by the end of the year and phase 4 trials will be starting.

People, the numbers of subjects in phase 4 trials is BIG. HUGE! Phase 4 trials take place after the FDA approved the marketing of a new drug. The drug is made available to the public through local physicians. They look for effects and side effects in diverse populations.

What this means for you is simply this: the first actual TREATMENT for geographic atrophy may only be six months away! This is the first breakthrough!

Lampalizumab is an injectible drug. It has been proven to slow the progression of geographic atrophy and to “reduce the area of geographic atrophy” by 20%. Dosing occurs monthly or every six weeks.

Will I do it? Probably. I really believe stem cell replacement of RPEs is the way for me to go, but it is taking forever and I don’t have time for forever. Lampalizumab can be administered locally and would avoid lots of trips to Philly. I don’t like the idea of intravenous injections but I don’t like the idea of a vitrectomy either! A 20% decrease in disease progression might win me enough time (and macula!) to have a more successful intervention later.

If you have dry AMD and geographic atrophy, it might be worth your while to broach the subject of lampalizumab with your retinologist. Let him know you are interested. This could just be the start of something big for all of us.?

Continue reading “BIG News!”

Sisters Are Doin’ It For Themselves

I have paid a lot of attention to the male movers and shakers in vision research. Perhaps it is time to note the contributes of the women. Recently I have come upon short articles about the research of two.

Sally Temple, SUNY-Albany, and her colleagues recently published a paper on how nicotinamide can suppress the progression of AMD. Nicotinamide is a vitamin B3 derivative.

Dr. Temple took pluripotent cells, that is stem cells, from people who had AMD and those who did not. She manipulated the stem cells to become retinal pigmentation epithelial cells and grew them in her lab.

One of the first things Temple and her team noted was the cells from the AMD people acted differently from the RPEs grown from healthy subjects’ cells. The cells from people with AMD produced different chemicals. The chemicals were the same ones that figure in the production of drusen and contribute to inflammation.

These were RPEs growing on a culture medium in a glass dish. There was nothing else to contribute to the formation of the chemicals. The chemicals had to be coming from the RPEs. And, with no other possible influences, the cause for the production of these chemicals pretty much had to be genetic.

The fault, dear readers, is not in ourselves but in our genes. One more tally in the genes are destiny column.

But the good news is, when they squirted (or whatever) nicotinamide on the offending RPEs, things improved. Chemicals that are responsible for the bad things were less and the RPEs survived longer.

Perhaps if we find a way to get nicotinamide directly into eyes, we will get the same results in vivo as in vitro. Worth a try.

Masayo Takahashi is a Japanese researcher. Takahashi has been experimenting using pluripotent cells taken from the same people they are going back into. No embryonic cells required.

There is excitement about this new procedure not only because of ethical issues. There are indications this procedure will be cheaper and faster to implement. In additional, they are thinking people can ‘bank’ their stem cells. These can be used either for ‘repairs’ in the original cell ‘owner’ or they can be given to other people who are immune matched. (Sort of like blood type matching. Don’t want the body getting up in arms over the ‘invading’ materials.)

Bottom line is the ladies are out there rocking it just like the men. They continue to come up with great new findings and each one takes us a little bit closer to effective treatments and maybe – just maybe – even a cure.

To copy Lin’s use of old song titles, “sisters are doing’ it for themselves”. And they are doing it for us, too! Continue reading “Sisters Are Doin’ It For Themselves”

Electrician’s Nightmare

Rods and cones. I learned those words back in the sixties in science class. We were studying the eye.

Rod cells are concentrated in the peripheral sections of the retina. They work well in dim light. They play a key role in night vision. While we need rod cells for good, overall vision, they have their limits. Rod cells are lacking in sharp vision and color perception.

That brings us to the discussion of cones. Cones are located most densely in the center of the eye. Their jobs are to see sharply in bright light and to easily perceive color.

Considering many of us have trouble with sharp, central vision and ‘wash-out’ in bright light, as well as have trouble with color perception, it comes as no surprise that we, those with AMD, are a little short on cone cells. If you have seen images of the ‘divot’ in your macula, that cone-shaped hole should be full of cone cells. Mine is not.

Because we are a bit short on cone cells, cone cells were what researchers were trying to grow for us. After a number of years the breakthrough came at the University of Montreal and was published in 2015. The head researcher was Gilbert Bernier. Merci, Gilbert!

Dr. Bernier came to the idea there must be something that helps to grow all those cone cells in the macula. After all, the embryonic cells are pluripotent. That means they are capable of becoming any one of several different cells. What makes it so these particular cells became cone cells?

Bernier discovered a protein that limited the stem cells to becoming pretty much only cone cells. He actually achieved about 80% purity, a pretty much unheard of accomplishment before this.

Even more exciting, Bernier’s cells organized themselves into nice, pretty sheets of retinal tissue. Not a disorganized mess.

And if that were not enough, when his cells were injected into the eyes of healthy mice, they migrated to exactly where they were supposed to be!!!! Stem cells with the homing instinct! Pretty cool. They were doing the happy dance in Montreal.

This is a huge step but not yet the answer to replacing cone cells, the photoreceptors we lack, and ultimately our vision. As I have said before, the cone cells grown in the lab are like cell phones without a tower. They do what they should do but have no way to send the signal to the brain.

According to the Discovery Eye article on the optic nerve and how it links to the brain, there are approximately 125 million photoreceptors, rods and cones, in the human eye. These connect to two, different intermediate neuron types and 23 different kinds of other retinal ganglion cells. Some of the retinal ganglion cells communicate with as few as five photoreceptors.

In short, the eye would be an electrician’s nightmare! It is no wonder no one has been able to figure it out yet.

There is, however, a way for it to be done. The knowledge of the body – remember these cells both organize themselves and migrate accurately – is miraculous. The next step is finding out how to give the connect order. I suspect the Montreal crew is working on it even now.

Bonne chance, Gilbert, bonne chance. [“Good luck, Gilbert, good luck” for those of us who don’t know French.]

written April 14th, 2017

Continue reading “Electrician’s Nightmare”

Kids and Zombies

This page is going to be another mixed up affair. I don’t have a full page on either of a couple of totally unrelated topics. Hope you don’t mind if I cobble them together.

First thought: I have talked about loving my big people and have not said anything about my little people. Let me correct that. I love my kids!

We may have an exceptionally tolerant and loving group of kids at our school, but I don’t think so. I think kids are just naturally adaptable and loving. It is the nature of the beast.

Anyway, my kids are wonderful. They take my telescopic glasses and CCTV in stride and think they are cool. My disability? Yeah, she doesn’t see well. What else is new? So what? Can we move on now?

The other day I was waiting for my ride, sitting in the office with all my gear. A little girl about seven was waiting for her mother. The little girl asked about my stuff and I first told her I have an ‘old lady’ eye disease. I think I am going to take this little darling home with me! Her response was “you are not an old lady!”

Then I told her I used the equipment to help me so I could continue to work with the kids at school just like I like. Her response? “Thank you”. OMG. I love my kids.

Second topic: Back to stem cells. Lin gave me an investment article. It was dated July, 2016. Mark Collins writing for marketexclusive.com suggested people invest in….drum roll, please….Astellas Pharma!

For those of you who just walked in, this is the company sponsoring one of the stem cell trials I am signed up for. I am thrilled to hear that this company is being touted as a good investment opportunity. It means the company is seen as a moneymaker. And how are they going to make money? By bringing the stem cell treatment to market, that is how!

Collins cautions this is a somewhat long-term investment. It may be two or three years until the product is brought to market, but the financial analysts are very positive about its future.

I am signed up for phase 2 clinical trials. If Collins is accurate in saying they should come to market by 2020, phases 2, 3 and 4 will have to come about in pretty short order. Good.

One more quick note: please remember RPE stem cells may stabilize vision. That means things won’t get worse but they won’t get better either. There is a bigger maybe for restoring some vision. Subjects in phase 1 got a few letters (not lines) on the eye chart back. RPE stem cells do not cure AMD.

Geographic atrophy, aka advanced dry AMD, means I have dead photoreceptors. Dead is dead. No zombies are produced in this procedure. That means it is not a cure. They are working on a cure but it is not expected for at least 10 years.

[For a review of what RPEs and photoreceptors do, see Sue’s page The Science Stuff.]

As always, I often do not know what I am talking about, so please check the stock tip with your broker….but if you make a billion dollars? Remember me! ? Continue reading “Kids and Zombies”

The Cockeyed Optimist

One of the books nephew #2 considered necessary for educating Aunt Susie was Steven Johnson’s Where Good Ideas Come From. I listened to it and it came to mind today when someone insinuated I was perhaps naive to have such faith in stem cell research.

I will eternally be a cockeyed optimist but I don’t believe I am unrealistic. Johnson has a concept I call “you can’t get there from here” and he refers to as the adjacent possible. Have you ever wound your way through a large museum? You cannot get from the marine invertebrate section to the land vertebrate section. They don’t connect. However by traveling through marine vertebrates, you find your way. Same concept. We are not in the stem cell cure ‘room’ and we cannot get there from here. But if I can help the researchers get into the next room, maybe even the one next to the stem cell cure room, I want to help.

Truth of the matter is, astounding leaps and eureka moments are rare. It is important to support the people finding the slightly closer rooms, one room at a time.

A reason to be optimistic? The bigger the network the faster the innovation. The more people working on a project, the faster dead-end lines of inquiry are abandoned. One person’s findings spark an idea in someone else. We are climbing onto each other’s shoulders to reach higher and farther than any other time in history. Open exchange of ideas is spurring us ahead at an incredible rate.

Johnson even reports error is necessary for growth. This goes way back to genetic mutations. How boring the world would be if everyone were identical.

Variation through error allows for variations in thinking and even serendipitous events. Knowledge advances through errors almost just as much as it does through linear, accurate discoveries.

I appreciate people are concerned about me. I really do. I like when people want to protect me. It is a nice, warm fuzzy thing. But I am not going into this with crazy, pie-in-the-sky expectations.

My hope is to stop the progression of the disease in one eye. The phase 1 subjects got some acuity back because dying photoreceptors were revived. That would be nice.

After that I am on the 10 year plan. Vision in 10 years is my tentative goal. Might happen. Might not. I am cautiously optimistic.

Did I choose wrong with stem cells? No. There is another author my nephew recommended, Malcolm Gladwell. The book Blink by Malcolm Gladwell refers to a concept known as the adaptive unconscious. The adaptive unconscious makes decisions without conscious contemplation. It is knowing without knowing how you know. Some people call it intuition. Gladwell has discovered the collective unconscious is very frequently right. The adaptive unconscious was how I first came up with my plan.

Hold it to the scrutiny of the conscious? Of course! Looking at the pros and cons of everything – repeatedly as situations change – is necessary. After all, I am not naive ?.

Have a great day!

Love, the cockeyed optimist Continue reading “The Cockeyed Optimist”

The Waiting Game

Yesterday was my third appointment with Regillo. Quite frankly I was hoping for great things. Hoping I would get a definitive answer and it would be positive! No such luck. My ‘answer’ was another “maybe”.

What criteria are they using? No clue. I was told my eye condition certainly qualifies me. Beyond that, I got no inkling of what I need to do to move up the list.

After a year and a half, I am getting more and more frustrated and antsy. If there is a way to become a prime candidate, I don’t know what it is.

Anatomy of the eye-click on the image for more information

I did learn a few things. Contrary to what I read, the good doctor says everyone has a suprachoroidal space (SCS). [Lin/Linda here: the SCS is the space between the sclera (outer part of eye) and choroid (space below RPEs). It’s important in both clinical studies Sue is referred to because both insert the stem cells into this space; more about the clinical trials below). Not sure why the difference between what I read and what he said. I know I read something about ‘forcing’ (my term) an SCS in guinea pig eyes. They did it by injecting saline solution between the appropriate layers. Maybe the difference is between having a space and having a medically useful space? I might be wrong but I got the impression the delivery system works better when there is fluid in the SCS. Maybe not. Anyway, everyone has one. I am just not sure if you need the fluid to accommodate the delivery system. If you really want to know, check with your eye doctor. I am still trying to piece this all together.

The next thing I found out was the Ocata/Astellas study may resurrect sooner than I was originally told. I had heard two years or more and now I am being told 2017. Sweet.

I was asked which one I preferred. The one I would prefer is the first one to come to fruition! I will be dancing in the streets to be asked to participate in either one of them.

So that is where I stand now. I have been given two strong maybes. Is that a guarantee I will get something or do two nothings equal nothing? It is driving me crazy!

So back to practicing my distress tolerance skills. I have to ACCEPTS my situation. Engage in activities and contribute to others. I have to compare my situation to those of others and be grateful; things could be worse. Doing things to laugh will help me to have opposite emotions and I can push away problems I cannot solve at present. I can also have pleasant thoughts and intense sensations that distract me from my frustrations. It can be done. I have done it for a year and a half. I can keep on.

written 12/16/2016

Continue reading “The Waiting Game”

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Reversing Damage That Has Been Done

Restoring RPE Cells – Restoring Sight?

Warning

Beware Unproven So-Called Treatments

Unreliable Resource

Stem Cell Research for Retinal Repair

The Basics

Summary of the Concept

The History

Next: RETINAL REPAIR USING STEM CELLS: PART 2 – CURRENT STATUS 2020

More Research

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Next: Happy Anniversary – Celebrate the Successes!

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Next: A MINOR EPIPHANY

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Next: Coping: A Review

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Next: Combination Therapies

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Next: The Patch

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Next: Furious and Proud

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