Category: Genetics

Sue on Assignment: Mitochondria – Part 3

In the interest of full disclosure, I would like to say this: I appear to have screwed up. I could have sworn I read Stealth has gotten FDA fast track status for a phase 1 clinical trial of its mitochondria treatment, elamipretide. Not exactly. It is a phase 2b trial and not a phase 1. Consider this to be my correction and my apology. Mea culpa. Mea culpa. [Lin/Linda: Sorry, Sue, I can’t let you take all the blame. I didn’t catch it, either. Sorry about that.]

According to a Medtran article on clinical trial phases, phase 2a trials are to evaluated the short-term safety of a drug. Sounds like phase 1 redux to me. The phase 2b trial is to start to check the efficacy of the treatment. It is also used to determine dosage range.

The press release Lin sent me appears to be where I initially saw the new drug is injected subcutaneous. That is under the skin. That is that mystery solved.

The dosage schedule is to be daily for 24 weeks. Read six months for that. Zounds. I don’t like the idea of having to go monthly!

I looked up elamipretide + age-related Macular Degeneration on clinicaltrials.gov and got one hit. It was the phase 1 study that was done with 40 people at Duke University in Durham, North Carolina. This study was listed as active, not recruiting. Either phase 1 is not totally finished yet or they have not let the clinical trials.gov people know it is finished.

Looking back on what Stealth published in 2016, I found they were looking for people with intermediate AMD in at least one eye but no geography atrophy or, for a second group, people with noncentral geographic atrophy. An exclusionary factor was having received “eye shots” to prevent blood vessel growth (anti-VEGF treatments.) This study appeared to be totally for those with dry AMD. I am assuming the experimental design and exclusionary criteria for phase 2 will be the same.

It appears information on all of this is rather sparse right now. We will keep our eyes open and see what else we can learn.

And my boo boo? Ahhh, really sorry about that.

Written December 22nd, 2018

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Sue on Assignment: Mitochondria – Part 1

Hi, again! I am not exactly on assignment for this piece. More responding to a couple of messages we received from a Facebook member. She was expressing excitement over new research on mitochondria. Lin and I knew little to nothing about this line of inquiry and I decided to look a little more closely.

Mitochondria. I have defined this word before and will do it again here. First of all, mitochondria contain their own DNA. This DNA is different from the rest of the DNA in your body. Why? Thank you for asking. The reason is this: the DNA in the nuclei of your cells comes from both parents. The mitochondrial DNA comes only from your mother and your grandmother and your great-grandmother and so on into the recesses of history. Sort of neat when you think about it. Anyway, the head of a sperm is 23 chromosomes packed into this itsy, little package. Nothing else in there. The egg, on the other hand, is relatively massive. The egg contains all of the parts cells have. This includes mitochondria. Ergo, your mitochondria is the same as every female in your mother’s direct female lineage. It can also be found in the male children of these women. In other words, when it comes to mitochondria, girls rule!

And mitochondria don’t have any old, little job. Every cell in your body, and by extension you, is alive because of the tireless work being done by the mitochondria. Mitochondria are described as the powerhouses of the cell. It is their job to mix oxygen with nutrients and produce ATP, adenosine triphosphate. ATP is the fuel for the cell. No, ATP, cells die. Cells die; you die. Thank mitochondria for your life.

Mitochondria also do other things. In Mitochondria and the Many Disorders That Compose Mitochondrial Disease they reported mitochondria have other duties tied to the specialized duties of the cell in which they are lodged and these duties change as we age. It is these other functions of the mitochondria that can lead to problems.

All of which is a rather long-winded way of saying it is looking more and more like some eye disorders are related to mitochondria malfunctions. Age-related Macular Degeneration might just be one of them.

Back in 2015 when the above mentioned piece was published in Mitochondrial Disease News, they cited work being done by a company named Stealth. Stealth was working on Ocuvia, this was a topical treatment for back-of-the-eye diseases such as AMD. Although only tried in non-clinical trials (read “rat lab”), Ocuvia was hoped to have a protective function for mitochondria. The medication was hoped to be able to deal with excessive oxidative stress and decreased energy supplies to the cells of the eye.

In the words of Artie Johnson (Laugh-in, 1968 to 1973), “very interesting.”

Lin gave me a couple of articles to look at concerning what Stealth is doing now. It would appear they are following this course of inquiry and looking for ways to treat mitochondria and AMD. Get back to you later on that. Bye!

Written December 12th, 2018

Next: Sue on Assignment: Mitochondria -Part 2

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Sue on Assignment: Mitochondria – Part 2

Like I said, it looks like they are now investigating the role of mitochondrial DNA in retinal diseases. Researcher Christine Kenney proposed damaged mitochondrial DNA sends signals that cause retinal cells to die at an increased rate.

Since a woman passes her mitochondrial DNA to every one of her offspring – unchanged except for possible mutations – and each of her female descendants passes the same mDNA to her offspring, it is possible to trace maternal lineage fairly easily. And you want to hear something wild? See Wikipedia for more data but suffice it to say here, researchers believe they have located the time and region of the most recent, common, female ancestor for us all. Or at least of whom we are aware. This woman lived in sub-Saharan Africa about 150, 000 years ago. How many greats Grammy would THAT be? Wow.

Now, since then mutations have happened and subgroups – referred to as haplogroups – have been produced. And that gets me back on track here. Kenney discovered our family members who are Jewish and originated in Central and Eastern Europe – you can think of them as Aunt Millie’s kids in Cleveland if that makes it easier for you – have much more AMD than Aunt Mary’s kids in Dallas. Those family members are black and came from Africa.  For all intents and purposes, the only  consistent difference between these two branches of Mom’s family is their haplogroups.

Hmmm, the plot thickens.

Nw, the problem becomes, this is just one more line of inquiry for AMD research. We thought we were looking for the needle in two haystacks – nucleus genes and environment – and now we are looking in three! We have to add mDNA to the list!

Kenney has decided to concentrate on the mDNA “haystack”. She has compared the Ashkenazi Jews (Aunt Millie’s kids in my little family saga) to Aunt Margaret’s kids. Aunt Margaret’s kids are white, Western European.  Aunt Millie’s kids have major differences in cholesterol and lipid metabolism, different inflammation and complementary genes and they have different sensitivities to amyloid, a toxin found in AMD and Alzheimer’s disease.

It would seem Kenney is on to something.

Fast forward to this week. Stealth Biotherapeutics has been granted FDA fast track status for elamipretide, a mitochondrial targeted treatment for dry AMD. This is a phase 1 study and is concerned with safety and tolerability only. This stuff is very early in the game. [Lin/Linda: both Sue and I missed the part of this press release that says, “In early 2019, Stealth plans to initiate a Phase 2b, randomized, double-masked, placebo-controlled clinical study to evaluate the safety and efficacy of subcutaneous injections of elamipretide in patients with dry AMD with geographic atrophy.” Sorry about that!  You’ll see that we’ve added a page to this series – see the link below.]

Elamipretide is hoped to restore the mitochondria’s ability to produce energy. It can be applied directly to the eye or injected. I thought I saw it could be a standard injection and not an eye shot, but now I cannot find where I saw that. Don’t hold me to it.

And there you have it. Here is another, possible line of inquiry for discovering what is happening to our retinas. And more importantly, in trying to stop and maybe even reverse it. Here’s hoping!

(And a special thanks to our cousins, those of  Ashkenazi descent, who are participating in this research. Their mDNA makes them like Baby Bear, “just right”,  for the research. Their willingness to help might take us to a cure.)

Written December 13th, 2018

Next: Sue on Assignment: Mitochondria -Part 3

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Our Cub Reporter: Notes from an Awareness Program – Page 4

Continued from page 3.

Personalized Medicine for AMD – Genetic Testing & AMD

Greg Hines is the CEO of ArcticDx, the company that is leading the way in genetic testing for macular degeneration.  He lives in Canada and his mother and sister both have suffered from Wet AMD.  They have bad genes for oxygen metabolism and they both smoked.

99.9% of each of us is identical and the medical industry relies on that sameness.  60% of AMD risk is genetic and 40% is lifestyle.

The Macula Risk Test is prognostic (gives information about the future) & pharmacogenetic (gives information about eye vitamins).  The Macula Risk test is 90% accurate at predicting which 15-20% of people with drusen will progress to advanced AMD.  Vita Risk is the test for zinc risk in eye vitamins.

OCT & fluoroscopic angiograms can sometimes see early wet AMD before vision loss, but this is difficult.

The AREDS research started in the early 90s with results published in 2001 and was sponsored by the National Eye Institute (NIH).  Risk of progression from moderate dry AMD to either wet AMD or geographic atrophy (GA) was reduced by 17% with antioxidants alone, 21% with zinc oxide alone, and 25% with antioxidants & inc.  Bausch & Lomb & NEI (National Eye Institute) make $270,000,000 per year from 3,000,000 patients and other competitors create a $500,000,000 annual market for these vitamins.

Greg asked the question:  Is the 25% risk reduction for everyone with AMD?

A series of studies have been completed over the past 10 years that seem to show that some AMD patients are hurt rather than helped when zinc is part of the eye vitamin.  The NEI said that the differences “weren’t significant”.

A 2016 study by Seddon et al from Tufts & Harvard found that 2/3 of the AMD patients saw risk reduction from 35 – 85%, but that 1/3 of the AMD patients – with certain genes – saw an increase of over 150% in the progression to advanced wet AMD.  This group had the same C1A0 & C2A0 genes.

All the accepted early research combined progression to dry advanced AMD (GA) with advanced Wet AMD.  If you only look at those who progress to wet AMD, the statistics show clearly that zinc is dangerous for these gene types.  Only three studies have focused on wet AMD.

Medicare was ready to approve reimbursement for the Vita Risk test until AAO (American Academy of Ophthalmology) and NIH got them to rescind the approval.

AREDS2 and lab tests are not regulated by the FDA, but the FDA can make manufacturers put warnings on labels.  The FDA has been requested to put such a warning on AREDS2 and its clones that contain zinc.  After this request was submitted on 5/8/18, meetings were held with the FDA, and they have agreed that there is an “indication of harm” for 13% of patients.

Harvard University put out a Press Release from its Dept. of Ophthalmology which “Confirmed that 15% of patients are harmed by a 300% increased loss of vision”

“DO NO HARM” is still the Doctor’s oath.

Macularisk.com has a list of eye vitamins without zinc.

Greg was our most impassioned speaker and got the most applause from the entire conference.

He is our Facebook group’s own Rock Star as is another person at ArcticDx Gerry Belgraver – along with Sue and Linda!!

Lin/Linda here: Thanks for your kind words, Joann, and for your GREAT reporting!  For more information about the AREDS studies and about zinc, click here for Eye Vitamins: Part 6 – What’s all the talk about zinc? Introduction.

Brighter Every Day

Greetings from what appears to be Pennsylvania’s version of monsoon season. Good grief. Tis wet out there!

This is going to be yet another hodge podge of unrelated ‘stuff’. Bear with me if you can.

First of all, I want to thank all of the kind people in the world and encourage you, if you are not going out because of fear of the stigma of vision loss or whatever, to get out there. Remember I told you I got left the other week? Strangers at the Y who saw that debacle are now checking on me. Do I have a ride? Be sure to say something if I get stuck again.

The clerk at a chain, sandwich restaurant gave me my change in $1s when I said I was visually impaired and needed singles for the van. 18 of them. Bless him.

Then there are my high school friends who drove 80 miles to have lunch and ‘catch up’ and the woman at Zumba who volunteered to give me a ride to Mom Prom and a dozen other people who look out for me and drive my sorry self around. Thank you!

Really. The more you get out there the better life will be. People are basically good and helpful. They will look out for you.

And in other news, I got lifetime dog licenses for the puppygirls. They offer a cut rate to the elderly and/or disabled. It should be about half of what I would have paid if I had bought licenses for the next 13 years. Saving money is a good thing. If you have younger dogs check it out.

NFB Newsline is expanding their offerings. They are now offering a children’s magazine, Stone Soup, as well as Sports Illustrated Online. These are in addition to Sporting News, Globe’s Israel and Science X, not to forget Medical Xpress and the newspaper Concord Monitor.

Remember Newsline comes to you through your phone, including landlines for people who don’t like their electronics to be ‘smart’. They offer a wide variety of local newspapers and you just may find some local news to listen to with your morning cup of coffee.

What else? Well, I found a healio.com article that talked about using immunosuppressants more frequently in Ophthalmology. This April 14, 2018 article did not mention AMD as a target condition, but given that AMD is thought to be related to immune system problems, they may want to look at the utility of immunosuppressants sometime down the line. My point in mentioning it was to show research in Ophthalmology is branching out in many different ways.

And case in point, remember the gene therapy for Leber congenital amaurosis that was developed in Philly and approved by the FDA? The really expensive one, Luxterna? The doctors at Bascom Palmer just injected Luxterna into the eye of a nine year old. His family is starting to see improved functional vision in this child. [Lin/Linda: actually, this March 23rd article says that there were 2 boys who were injected with Luxterna.]

And one more before I go: retinitis pigmentosa is a retina degeneration disease that leads eventually to total blindness. GenSight has gotten MHPRA approval to run clinical trials of gene therapy for RP in the UK. (Alphabet soup, anyone??) Why get excited about that in an AMD blog? To quote the GenSight CEO “If proven safe and effective, this therapy could be transferable from retinitis pigmentosa to dry AMD.”  [MHPRA stands for Medicines and Healthcare Regulatory Agency and is the UK’s equivalent to the US’s FDA.]

Oh! That’s a good reason! Things are looking brighter every day!

Next:  I Got This

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News Briefs

Dreary Saturday. It is cold and rainy. The chill gets into my very core. I would rather have a foot of snow than this stuff but then no one ever asks me. Also, a lot of people really don’t appreciate my preference for snow! Obviously not skiers.

All afternoon I have been curled up on the couch with my iPad. Decadent. Really don’t like to do this but I wanted to finish a BARD book I had started and I was working on level 1005 on Panda Pop. Make that STILL working on level 1005. Not going so well.

Anyway, I do need to mend my wanton ways…later.

My email is full of news briefs from eye sites. ? There is a ton of information out there. One article healio.com sent me was Specific gene variants play role in response to Anti-VEGF treatment. Once more it appears our genes are our destiny, at least for now.

We all know medicine is headed towards ‘personalization’. There is evidence for a vitamin supplement/genotype interaction and now it appears there may be an interaction between your ‘eye shots’ and your genotype. A study in Spain grouped together good responders and poor responders to ranibizumab (Lucentis). Then they did genetic testing on the two groups. Guess what. Genetically these two groups were significantly different. The genes that responded well were thought to be CFB, VEGFA and VEGFR1. Poor respondents had certain variants of SERPINF1 and CFH.

Among the non-genetic markers? Smoking and high blood pressure were both associated with poor outcomes.

In coming years it should be interesting to see what is going to happen between genetic testing and privacy rights. Also with genetic testing and attempts to withhold services. Will you have to pay more for insurance if you have ‘bad’ genes? Thinking I may be glad if I miss THAT aspect of our brave new world.

Healio.com also reported the Argus II was recently implanted in the eye of a man with retinitis pigmentosa in Singapore. Remember RP people are generally ‘big B’ blind. This thing is not for us who have comparatively good vision.

And for our friends with RP here in the States, Medicare will now pay for the Argus II in 28 states, two territories and DC. Recognition of such innovations as ‘medically necessary’ is paving the way for other innovations that will be coming. Read, accepting the Argus II for RP patients will ‘soften up’ policy makers so they are more likely to pay for things we as AMD patients will be able to use. I find that a lovely thought. (So I am manipulative, conniving and self-centered. Wanna make something of it?)

Pretty much it for now. I have not done much today and I am feeling like a bit of a waste of space. Need to accomplish something. Maybe just one more shot at that level in Panda Pop? ?

Written February 24th, 2018 Continue reading “News Briefs”

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! [click here for an article that talks about this in more detail.]

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”

Research: Dry & Wet AMD

Hello! I am going to get to the article Lin found on BrightFocus Foundation’s website about ‘lamp stuff’ aka lampalizumab but first I wanted to quickly mention a Google Talk by Isaac Lidsky. The title is Eyes Wide Open.

Lidsky began losing his sight to retinitis pigmentosa when he was 13 years of age. Although he has been totally blind for many years, Isaac Lidsky is extremely accomplished and has developed a philosophy that includes all sorts of concepts such as being present in the moment, doing what works and not abdicating responsibility for your life to your personal heroes and villains. His half an hour Google Talk may make some people rethink their attitudes towards their sight losses.

While I don’t expect many people to feel ‘lucky’ they are going blind – and Lidsky does consider his blindness to have been a blessing – Lidsky’s perspective on things can be thought provoking.

OK, onward to ‘lamp stuff’. We have quoted Joshua Dunaief before. One of the most helpful things he does for me in the current article is give us a pronunciation guide for lampalizumab. It is lamp-uh-liz-you-mab. Sort of like “Lamp!…uh, Liz, you mad/b?” You know, what you say when you knock over Elizabeth’s favorite light.

We have gone over the study results already in these pages. Complement factor I variant folks got kickin’ results. The rest of us, not so much. A reason for genetic testing for us before we submit to needles in the eyes, literally!

Dunaief says results are expected in 2018. Yep, December is their target date for publication. He does not mention phase 3 is over this December as is indicated in clinicaltrials.gov.

So, basically, still not really sure what is happening with ‘lamp stuff’ and me. May be offered it in December. May not be. May accept the offer. May not. I would love to know my genotype as compared to the SNPs they found in the experimental sample. Being a responder would be incredible. Being a nonresponder would be very bad. Dilemma.

And information for our ‘wet’ friends for my last 200 words. In JAMA Ophthalmology Jackson, Boyer and Brown reported the results of an experiment with an ORALLY administered vascular endothelial growth factor (VEGF) inhibitor. In other words, they have been experimenting with a pill they hope would do the same thing as your anti-VEGF shots.

The stuff is a tyrosine kinase inhibitor. It caused a lot of upset tummies and diarrhea (5 and 6 subjects out of 35 respectively) but the side effects were not bad enough to stop the experiment. Some people did stop because of liver problems. Those with liver issues would probably not be candidates for the treatment.

Only 40% of the total required rescue shots. Even those people received fewer injections than they had without the pills.

Before you all rush out for your X-82 pills, bear in mind this was a phase 1 experiment. That is safety and tolerability, guys. They are moving on to proof of concept, phase 2, with a bigger n. (n being the number of subjects in the study, remember). Check clinicaltrials.gov if you are interested.

Remember we all do our part in this fight. If you have a strong liver and a strong stomach, X-82 might be your kind of research. You might get to be a lab rat before I do!

written September 2nd, 2017

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The Winner Is…Genetics!

I just tried to read the article listing the different genetic variants that have been associated with AMD. The complementary system in Age-Related Macular Degeneration: A review of rare genetic variants and implications for personalized treatment is declared the winner!

I admit defeat! Maybe I can study genetics for a decade and come back for a rematch.

I can sum up what I learned in about two sentences. The great majority of SNPs associated with AMD appear to be on chromosome 1 where the complement immune system is coded. SNPs cluster around the location of Complement Factor H although there are also large numbers of mistakes in the neighborhoods of Complement Factors i,2,3,9 and B.

The second thing I learned is this: the rare forms of AMD are coded for in other places. These ‘outliers’ are being studied in genetically-isolated groups such as the Amish.

Side note: The Amish are a closed, religious and cultural sect. Pennsylvania is a population center for the Amish. Therefore, here in Pennsylvania they live in association with us although not necessarily among us.

The Amish have all descended from an initial group of about 200 families. Because of the close inbreeding they suffer from a variety of genetically based problems such as dwarfism, Angelman’s Syndrome and several metabolic disorders. Being such a ‘natural laboratory’ for study of the founder effect, the Amish have allowed much genetic testing on members of their community. One of the conditions studied? Age-Related Macular Degeneration.

For more information on the Amish, check Wikipedia or your favorite reference.

OK, so it is not strictly info on AMD, but man does not live by vision loss news alone. I find that sort of stuff interesting. Hope you do, too.

And quickly back to the AMD stuff – because I only have about 200 words left – the Audacious Goals Initiative is still working hard to stamp out blindness. I found a better article on the mouse-zebrafish experiments on their page at the National Eye Institute. This article stressed how the Muller glia cells from the zebrafish had been able to be transformed so beautifully they were electrophysiological indistinguishable from interneurons cells. They had integrated well on both ends of the connection required and were sending signals to the brain. In other words, the zebrafish cells had changed and connected so the blind mice could now see.

Very preliminary work but exciting. The article cites a lot of problems such as: there are not quite enough zebrafish eyes to satisfy the demands of potential research. It might be best to find ways of coaxing regeneration of existing cells in our own eyes. Save the zebrafish!; you understand.

Just one more amazing bit of research and discovery that some day will eliminate Age-Related Macular Degeneration and allow people to see….I’m just glad there are people out there who are a helluva lot smarter than I am to do the research. Now, anyone want to explain the genetics to me?

written August 27th, 2017

Continue reading “The Winner Is…Genetics!”

Another Potential Treatment

The more I look into this, the more overwhelming it seems! I am glad I never tried to be a geneticist!

What am I talking about? The latest information on treatment for geographic atrophy suggests there is another gene being targeted. The gene is C3.

Remember how I have been saying Age-Related Macular Degeneration is looking not like one disease but like a family of diseases? When I followed up with some background research on complement factor C3, I found a list of – get this – over 3 dozen different SNPs that preliminary evidence suggests have a role in causing AMD. Remember SNPs or ‘snips’ are genetic coding errors. Some are beneficial. Some are neutral and some can really screw thing up.

Anyway, it appears there are literally dozens – if not more – of ways we can be ‘wrong’ to get AMD. Right now that means they are working on finding dozens of ways to intervene. May be a panacea sometime in the future, but right now they are nibbling at the problem a piece at a time.

And the piece they are nibbling on now is C3. According to a short article by FierceBiotech, Apellis has finished phase 2 – the proof of concept phase – trials with intravitreal injections of a drug they are calling APL-2. Later it will get a trendy brand name but for now look for APL-2.

BusinessWire identifies Apellis as a company “developing a platform of novel therapeutic compounds for the treatment of autoimmune diseases” so I guess people are coming around to see AMD as an autoimmune disease. APL-2 is described as a complement factor C inhibitor. It “binds specifically to C3 and C3b, effectively blocking all three pathways of complement activation (classic, lectin and alternative).” That sort of sounds like it is suppressing ‘friendly fire’ sooner in the process and may be closer to the ‘one treatment fits all’ that we would like to see. Not anywhere near there, but closer.

The results were very promising. At 12 months they showed a 29% reduction in growth as compared to sham.

But the weird – and great! – thing that happened was this: during the second six months of the study, the reduction rate was 47%! For some reason, the effects of the treatment appeared to be cumulative. Pretty cool.

Now I am not sure what type of genotype you have to have to profit from treatment with APL-2. The researchers are not sure at this point either. They decided to do some searching for genetic markers. Being the suspicious sort, I am wondering if they had star responders and non-responders just like they did with lampalizumab. Would make sense. Why do genetic testing on an ‘n’ of 246 people if you don’t have to? It’s expensive.

And speaking about money, there is a lot of money to be made with this drug. Apellis wants to get APL-2 to market quickly so it can compete with eculizumab, a treatment for PNH, a blood disease. (Apparently PNH is also related to complement factor C). Their competition, Soliris, was predicted to bring in more than $3 billion in 2017. Sometimes a little greed is a good thing! $3 billion can really motivated people.

So, there you go. It seems they have found one more way to save some of the sight of some of the people some of the time. Number two potential treatment for our ‘untreatable’ disease. The wall is coming down a brick at a time. There is hope.

Here’s another article about APL-2 that says “APL-2, a complement C3 inhibitor, has met its primary endpoint in its phase 2 clinical trial, reducing the rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD).”

written August 27th, 2017 Continue reading “Another Potential Treatment”

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