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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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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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

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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

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Yesterday’s News

Good morning! Lin just shared a video clip from something that looked like a local TV, health program. The clip was on geographic atrophy. That is GA to those in the know.

I have no problem with information being shared with the public. In fact, I think it is a good thing. The more exposure we get and the more noise we make I am hoping two things will happen. One would be law makers (read the deep pockets of government) will be more aware and sympathetic to our plight. (They might also come to realize it is going to cost BIG bucks to care for us!) The other will be people who have AMD will become more knowledgeable and go for help and support.

There are some drawbacks to these little TV presentations, though. For one, they are a bit behind the curve when it comes to breaking new news. The show talked about a fantastic, recent development that would help people with GA.

Fantastic? OK. Helpful? Yep. Recent? Only if you consider research published in 2013 to be recent.   So shoot me. I am an information snob. That information was just too yesterday’s news for me.

I also think they present half information. If you listen to the clip you will hear the expert talk about a ‘subset’ of patients who cannot be helped with current treatments. Not to put too fine a point on this – and look out because I can feel myself getting ready to rant! – but, honey, the group that can be helped with current treatments is the subset! 15% of AMD patients ‘go wet’. The 85% of us who are left are not the subset! (Told you I was going to rant!)

In the clip there is the implication that replacing RPEs will restore sight. We have talked about this a dozen times before. In GA the photoreceptors are dead. There is no sight without photoreceptors. The RPEs are support cells for the photoreceptors. They do not do any of the ‘seeing’.

But my big complaint about this clip? The expert says your world ‘ends’ when you develop GA!!! (Now I am really revving up. Head for the storm cellar!)

With every significant loss, there is a time of dismay and distress. That does not mean the end of your world! Everyone of us here is made of tougher stuff than you could ever have believed. Maybe you have never been tested before, but the steel is there.

Today I taught my class. I attended a staff meeting and saw two clients. Then I came home, walked the dog and made a meal. I am now writing this page. After that I have a psych report to write. Then maybe some down time ‘reading’ a BARD book.

Tomorrow I work, walk with a friend and go to my yoga class. I am making plans to go into New York City with a co-worker next month. The list goes on.

In short, if my world ended a year and a half ago, nobody bothered to tell me about it! I am still going pretty much full tilt!

So, bottom line? I guess it would be listen to the stuff in the media but remember it might not be accurate or current. Once again, caveat emptor. Best sources still remain published research. If you cannot read it or cannot understand it, ask Lin or me to look at it and we can tell you we don’t understand it either!

And about that end of the world business? Don’t believe everything you hear! GA is not a walk in the park. However, if you want to, you can still do that and dozens of other things as well.

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The Blind Spot – Part 2

Lin found about the best article on scotomata that I have seen thus far. It has some basic information. Stuff that I had inferred from other articles but had never been defined.

Scotomata are areas of vision loss surrounded by intact vision. Scotoma, as I said, is Greek for ‘darkness’. Again, not a happy thought.

A scotoma can be in one eye or two. It can be physiological. Everyone has a natural blind spot where your optic nerve is connected to the retina. We don’t realize it because our brain just fills in. No need to worry about physiological scotomata.

Scotomata can also be pathological. Because these are the result of a disease process, these are the ones we get to worry about.

Relative scotomata are the kind you can ‘see through’. You no longer have a full complement of cones but enough remain to sort of get the job done. I have relative scotomata in my eyes. Unfortunately, one of them probably just had a massive die off because it has gotten several shades darker.

When the scotomata go black you have something called absolute scotomata. Those are the areas in which the photoreceptors – in our case, cone cells – have pretty much all died.

A positive scotoma is one that is obvious to the owner of the eye. I KNOW – I am in fact positive! – I have blurry spots and I am aware one of them just darkened.

We had a comment from a reader who has a negative scotoma (maybe two). She wrote she quit driving when cars on the road would disappear and reappear. Her brain was ‘filling in’ the blank spot with a vision of an empty road.

Aren’t brains just amazing? Scary, but amazing. After all, that little trick could kill both the brain and its owner! (Or would that be its servant? Hmmmm….)

And that, my dears, is what I know about scotomata. Not much considering I am the ‘proud’ owner of two of them! Will they all progress to black? Dunno. I keep looking and asking and continuing to feel like a mushroom. You remember: keep me in the dark and feed me bullshit.

What I was told was it was not a conversion to wet. Reassuring but I never thought it was. I was told there was no obvious difference between my last OCT scan and this one. I guess that means the die off was not severely massive, only mildly massive (but I can still see the difference!!!).

I was also praised for being proactive with my vision care. Important for us all.

So, darkening of your scotomata apparently may occur. It probably means things are dying in there. That is my interpretation, though. I was told it was progression of the disease, but if you have a disease in which cells die, would not progressing be cells dying? Stands to reason; yes?

If you perceive a significant change in the density of your scotomata, call your doctor and go in for an OCT just to be on the safe side. Not much can be done for the progression of the dry, but on the off chance you are converting to wet, you need to catch it quickly.

Thus we end another ‘adventure’ in AMD. Anyone else having these problems? Sigh.

Continue reading “The Blind Spot – Part 2”

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SOS

J.R.R. Tolkien said once that “false hopes are more dangerous than fears.”

Every once in a while Lin and I hear someone make a claim about AMD that we know is not true. Then someone picks up on the claim, believes a foolproof treatment or cure has been found and they have been saved from blindness. This is only to have their hopes dashed a day or two later when the truth comes out. This can be heartbreaking to watch, let alone experience.

Right now, to our best knowledge, there is no cure or available treatment for dry AMD. There are a number of treatments being tested. Even the treatments most advanced in the process are several years away from being available to the general public.

The SOS has been sent. The cavalry is coming but they are still a very long ways away. It is up to us to hold out until then.

When I talk about medical treatments, I am talking only about drugs that will slow the deterioration process. To my knowledge there are no drugs that will regrow RPEs and/or photoreceptors. The drugs will not restore sight. If you have lost your photoreceptors, at this point in time you have lost your sight.

Stem cell replacement at present is for RPEs only. Remember RPEs are only servant cells. They take care of the photoreceptors. The pizza delivery guy may help to keep the neurosurgeon alive but we would not expect him to do brain surgery. Same concept. The RPEs will feed the photoreceptors but they won’t turn light into sight. The best we can hope for is for some of the photoreceptors that are at death’s door to be revived and start working again.

Dead photoreceptors are just that, dead photoreceptors. I have geographic atrophy. Photoreceptors that should be in that area are dead and gone. There is currently no way to get them back. The last I heard they were able to grow photoreceptors but they had been unsuccessful in having them connect with the rest of the nervous system. You have a cell phone in a deadzone. Your phone works great but the signal goes nowhere.

Am I saying have no hope? Hell, no. I live on hope. Just have realistic hope. Treatment is coming. Cures are coming. Just don’t expect them next Tuesday!

Why do people get so hung up by these crazy claims? First of all, they are desperate. Any port in a storm. Beyond that I am not sure. I wasn’t able to find a lot on the mechanisms behind false hope. Maybe it is better to feel better for a little while even if you are destroyed later. Sort of like substance abuse. It felt good at the time.

We try not to deal in rumors, just facts. If we say something you do not think is true, challenge us. If you read or hear something different from what you hear here, alert us to it and we will research it. Better yet, anybody capable of web research might volunteer to help us. There is a lot of information out there.

In the meantime, keep the faith but don’t go crazy. We are not there yet.

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