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”

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Our Turn is Coming

Happy Monday! Waiting for the van again so forgive me if I run off abruptly.

Back to the pink of health. I revised my evaluation and decided it was food poisoning….again?!?! My dining companion ate her leftovers and also got sick as the proverbial dog.

I was well enough yesterday to accept an invitation to go kayaking. Said if before, say it again, weird weather. There was some guy jet skiing on October 16th! Anyway, it was fantastic to be on the river. Warm breeze. Birds calling. Fishermen shouting greetings across the water. Kids on the bank asking me if it were nice out there. Yeah. It was. Really nice.

To business! I promised you RPE65. The Genetic Home Reference tells us RPE65 is also called retinoid isomerhydrolase. Yeah, whatever. RPE65. RPE65 is responsible for providing instructions for a protein we need to see. It is, obviously, part of the RPE layer.

As I said last time, RPE65 is essential in the visual cycle. Light changes a special molecule called 11-cis into a different substance. Since it is no longer any good for changing light into electricity in its new form, it has to be ‘recharged’ so it can go back to work. That is the job of RPE65.

With me so far?

Failure to convert the end product of the reaction – referred to as all-trans-retinal – leads to a build-up of said all-trans retinal as a waste product and a toxin. In my terminology, it is part of the eye poop. Your visual cycle also stops working. Not good.

Now, I am not saying we AMD folks have problems with faulty RPE65 genes. (Although we might. I am only a dabbler in the field.) Those mutations are found in diseases like Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). What I am saying is every breakthrough in one aspect of vision research might lead to breakthroughs in other areas and – drum roll please! – there has been a breakthrough!

Not all that far away from me, in the City of Brotherly Love, also known to us country folk as ‘Filthydelphia’, Philadelphia to all you other folks, they have found a way to ‘reprogram’ faulty RPE65 genes using gene therapy. Philadelphia is on a roll because this is the second gene therapy its researchers have had recommended for approval. That is the second of two, mind you, EVER recommended for approval by the FDA. Philly researchers have gotten them both. One more and they will have a hat trick! (Go, Flyers!….OK, so their decades were the 1970s, ’80s and ’90s, but it could happen again.)

The first gene therapy recommended for approval was for leukemia. The visual cycle gene therapy is called Luxerna. It is going to be offered to children with early onset blindness in a bid to keep their photoreceptors functional. It has a very high success rate and is still working in phase 1 subjects from four years ago!

So what happens now? Luxerna has been cleared to take the final hurdles. According to FDA.gov there are three more steps in a 12 step process. These steps are as follows: review of labeling information, inspection of manufacturing sites, APPROVAL.

Brave New World. Stay tuned. Our turn is coming.

written October 16th, 2017 Continue reading “Our Turn is Coming”

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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”

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Eye Poop Reduction

Looking for information on therapies that slow the vision cycle. Got all sorts of things on slowing traffic for safer cycling.

While I am all for fewer car/bicycle accidents, that is not exactly what I had in mind!

Back to Wikipedia, I discovered the visual cycle is the process through which light is transformed into electrical signals. If you have a penchant for chemistry, I refer you to the Wikipedia article. Social scientist here! As far as I am concerned…then there is magic!

Part of this magic includes having three different types of cone cells that respond to three, different wavelengths of light. By taking stock of the strength and blending of the stimuli from these three, types of cone cells, we are able to see color! Cool! Although my guess would have been the primary colors, the colors they detect are actually red, blue and green. Why? Dunno. Magic.

But back on track, visual cycle…

Since the job of RPEs is not only to feed the photoreceptors but also to clean up after them, RPEs have to be able to tolerate a lot of…uh, poop. (Gee, maybe I am just a big RPE! I feel like I deal with that stuff all the time!) When there is too much poop for them to handle, we get, among other problems, drusen.

Janet Sparrow in Therapy for Macular Degeneration: Insight from Acne (catchy title😫) said “it is the responsibility of the RPE to internalize the membranous debris discharged daily by the photoreceptor cell.” In other words, they eat eye poop. Unfortunately, some of the molecules in the poop are toxic (as if eating eye poop was not bad enough) and not at all good for the RPEs or surrounding cells.

The theory goes something like this: Less eye poop would make life easier for the RPEs. While we cannot get rid of all the eye poop – after all it is a byproduct of what we want: sight – maybe we can reduce the volume of how much poop we actually have to deal with. If we slow down the chemical processes involved in sight maybe we can produce less poop and thus see for a longer period of time.

They are checking out that theory right now. Foundation Fighting Blindness (FFB) advertised for subjects for a phase 2 (proof of concept) clinical trial of ACU-4429, a “visual cycle modulator”. For our purposes, read “eye poop reduction strategy”.

FFB also published a one page blurb about Fenretinide. Fenretinide has successfully completed phase 2 clinical trials and is on the way to phase 3. They are hopeful it will slow down the visual cycle in those with dry AMD. The slowing should lead to fewer lesions in dry AMD and fewer cases of wet AMD.

Oh, and that chemistry I referred to earlier? I might actually have to understand some of it. Oy. In the visual cycle there is a pigment-y sort of thing called 11-cis. Helping the light signal along its way to become sight causes a chemical change in the 11-cis. In order to get changed back to its original form so it can do its job again and not contribute to the eye poop problem, 11-cis needs help from several molecules, one of which is REP65. REP65. Remember that name. It may be an up-and comer.

written October 14th, 2017 Continue reading “Eye Poop Reduction”

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Maybe They Have Something

Good afternoon! It was a busy morning. My husband had to take the car for service so he dropped me off at the hospital for a shoulder x-ray and routine blood work. My shoulder pain is little better.

You would think I could just continue with up dogs, down dogs, planks, side planks and all those other yoga moves with no negative effects, but nooooo, my shoulder is really sore. It might have something to do with my not being as young as I used to be, but I doubt it.😊

Then I walked down to get a haircut and Pizza Hut buffet lunch. Picked up by hubby. Grocery store. This year’s photos to the camera store for display. Home.

I have cleaning to do. I have a report to write. Oh, well. I have an OBLIGATION to our website!

At the end of last year Lin did a page on topical treatment for wet AMD. That means eye drops instead of shots. One of the ones she talked about was Squalamine. At that time Squalamine had failed to satisfy the efficacy standard laid out and the trials had been terminated.

Squalamine had failed to reduce the number of shots needed to keep crazy, blood vessel growth at bay. However, there were some secondary goals that were reached. According to the January 29, 2017 VisionAware, there were positive effects on acuity. This was especially true in people with a specific type of lesion. 31% of the people with ‘classic’ wet AMD lesions gained 11 letters on the chart!

According to healio.com a classic lesion in wet AMD has well-demarcated hyperfluorescence in the early part of the test and progressive leakage later on. It is not to be confused with occult or combined lesions.

Ohl Pharmaceuticals decided in February, 2017 to take the 200 people already enrolled and start in on phase 3 trials. In April Ohl announced it was amending the timelines of the study so there could be results late this year or early 2018. They also amended their goal to be an increase in visual acuity as opposed to a reduction in shots needed.

Now, I am wandering into the area of unsubstantiated speculation here, so don’t take what I say as gospel. OK ? OK. The April 10th press release alluded to the research being funded until early 2018. To quote: “Following the close of financing today we are funded until 2018 including completion of our ongoing clinical trial and data readout by the end of 2017 or early 2018.” Now if that were me and I were getting positive results, I would want to show off those results quickly and improve investments and other funding. If I had squat, I would stall and plead for just a little more time and MONEY.

In other words, I think they have something.

Another reason I think they have something? The press release said they were working with the patients who had “the greatest potential to benefit from Squalamine combined therapy”. In other words, they stacked the deck. (In my opinion, of course.)

Anticipating they rock the phase 3 study AND the FDA gives approval to ‘go live’ in a reasonable amount of time, a combination Squalamine/Lucentis treatment could be available in 2018. Cool. We are on our way.

Written October 9th, 2017 Continue reading “Maybe They Have Something”

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Important Cells

You would think that after saying I was running out of ideas, I would have the good grace to actually run out of ideas and shut up. You should be so lucky!😎 [Lin/Linda: =I= should be so lucky! ::grin::]

A comment was made suggesting we may have fostered some misinformation. We have stressed the idea of retinal pigment epithelial (RPEs) cells supporting the photoreceptors in the macula so much we may have given some people the impression the RPEs are only under the macula. This is not true. RPEs are under all of the photoreceptors and support all vision, not just central vision.

Once again my very erudite source, Wikipedia (I did print out another article but it is long and involved and I can probably get three or four pages out of it. Do you really want that?) reports the RPE layer was first discovered back in the late 1700s, early 1800s. It was noted to be black in color in many animals but brown in humans. This is because this single layer of hexagonal shaped cells is chock full of – all together now! – pigment. The RPE layer wraps around the back of the eye and ends practically at the iris.

We have talked about a couple of the functions of the RPEs. They are there to feed and clean up after the prima donna photoreceptors – both central cones and more peripheral rods – that apparently cannot do things for themselves.

Something I had not heard of before but makes sense is RPEs, as the conduit from the bloodstream to the interior of the eye, are also the gatekeepers. RPEs are at least partially responsible for the immune privilege of the eye. Remember we talked about how the eye is such a great place to do stem cell experiments because the immune response is so weak? Part of that weakness is due to the great jobs the RPEs usually do. They block bad things entering our eyes from the rest of our system.

RPEs gather up scattered light to make images sharper. That also keeps the light from causing extra oxidative stress.

Simply put the visual cycle is the amount of time as well as all the steps it takes for pigment in the photoreceptors to be depleted and then build back up again. The RPEs do much to control this.

Lastly, the RPEs produce signalling molecules that ‘talk’ to different parts of the system. Lots of very important functions for a one-cell thick layer of cells.

Age-related macular degeneration is not the only condition that causes vision loss due to malfunctions involving the RPEs. A more common one you may heard of is retinitis pigmentosa (RP). Their losses start in the periphery and progress inwards. Those with RP go blind. That’s BLIND. Maybe we ARE the lucky ones.

Do I know why our deterioration generally stops at the macula? Nope, but I have it on good authority it usually does. Usually does not mean 100% guarantee. Just usually. It is the best that I can do.

written October 10th, 2017

Continue reading “Important Cells”

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Keep Calm and Carry On

I want to get this typed and out because Lin and I both suspect people will not listen to me or Paul McCartney and let the suggestion of atrophic damage beyond the macula be.

How can you not listen to Paul? He was my favorite Beatle when I was a teenager! Remember when the Beatles were on Ed Sullivan? [Lin/Linda: of course I do – I was sitting on the floor in front of the TV loving every second of it.]

What? Pertinence to the topic? Okay. Sigh.

Found an article based on research coming out of Seoul, South Korea. The research looked at peripheral reticular pigmentary degeneration (PRPD). That is lesions on other areas of the retina as opposed to lesions only on the macula.

Primero point: the authors say three or four times this type of degeneration is rare, rare, rare. They had trouble finding enough people to make their study valid.

Point segundo: patients with degeneration of the peripheral retina are significantly older than patients who do not have it. Yes, some of you are up there but most of us don’t have to worry about the truly advanced age factor for some time.

Point three, whatever that is in Spanish [tercero]: the most common, probably contributing factors in these people were factors related to compromised circulation. That was both systemic and ocular circulation. The biggies were found to be retinal artery occlusion, ischemic (low blood flow) optic neuropathy, and a couple of other ischemias. [Click here for more about these conditions that are sometimes called ‘eye strokes’.]

One that sort of scared me was a positive correlation with high blood pressure. However, last week my pressure was 122/78! Admire it now because I cannot tell you the last time it was so beautiful.

Other factors are as follows: stroke, carotid artery stenosis, and yes, AMD.

Now don’t get your panties in a bunch just yet. The theory is, once again, there are common, underlying factors leading to these conditions. AMD does NOT cause PRPE although the same may not be said in reverse. PDPR may promote the development of AMD.

They are looking at a shared genetic risk between AMD and PDPR. There is evidence a complement factor H variant is involved in coding for a propensity for PDPR just as it is thought to code for some (all?) variants of AMD.

Choroidal ischemia is a factor in AMD as well as PDPR.

So, bottom line here: this is a very rare occurrence, especially in younger oldsters. It is related to poor circulation. Circulation tends to get worse as we get older. It is also possibly related to variants in complement factor H.

Can’t change your genes just yet at any rate. Cannot get any younger. That leaves taking care of your circulatory system. Do what you can to improve it.

As an anonymous member of the British Ministry of Information said: “Keep calm and carry on.”

Our journey is not over yet.

written October 8th, 2017 Continue reading “Keep Calm and Carry On”

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