“Feed Me!”

We are having another dreary day. These days always manage to give me that napsy feeling. They also make me want to eat! Ugh.

I do much better when life is fast-paced and I am forced to follow along. If you want something done, ask the busy person.

So maybe if I want to get something done, I should force myself to be busy??? A bit of perverse logic there. Oh well….

I spent a few minutes today looking for new information on lampalizumab. There was nothing except business articles talking about the billions of US dollars Hoffman-LaRoche had been counting on before the phase 3 study failed to show a significant effect for the drug. I guess we need to wait for the research report to actually find out what went wrong. Everything out there now is all doom and gloom and speculation about what will happen to Hoffman-LaRoche stock.

I believe we talked about phase 3 of experiments like this. Phase 3 is a larger “proof of concept” phase. CenterWatch says 70 to 90% of drugs pass phase 3. Apparently most of the work is done in phases 1 and 2. With a statistic like that, now I am REALLY curious to find out what went wrong.

But, never fear, unlike Hoffman-LaRoche, we have not put all of our proverbial eggs in one basket! The article I was referring to in the page Recent Advances in AMD goes on to list quite a few different lines of research. In addition to research into anti-inflammatory therapies they are also experimenting with protective factors for the retina. Then add to those the experimental therapies that inhibit the visual cycle.

No, I am not exactly sure what that is either. My impression is it involves slowing the metabolism of the retina to cut down on drusen aka ‘eye poop’. Less eye poop to get between Bruch’s Membrane and the RPEs, the longer you will have usable vision. Sort of sounds like the low fiber dog food they marketed years ago. Low fiber was supposed to equal fewer ‘landmines’ in the yard. I don’t think that was good for puppies and I am not sure if slowing eye metabolism is good for eyes, but they are the experts so who knows?

Based on the theory neovascularization is caused by under-oxygenated, under-fed retinal cells screaming “Feed me!” like Audrey 2 in Little Shop of Horrors, they are also trying to increase the supplies to the choroid before the retinal ‘natives’ get restless.

MC-1101/MacuCLEAR is a vasodilator that has come through phase 1 testing and is ready for phase 2. That is a topical. They have tried several, other vasodilators with no or mixed results. One of the other ones they have tested is Viagra. However, Viagra did not help eyes at all! Sorry about that. (There goes that excuse for getting the script!😎)

Of course, the last course of investigation mentioned is stem cells. I think this may be where I came in. And I know it is where I am going out right now! Chat at ya later!

written September 10th, 2017 Continue reading ““Feed Me!””

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Bad Patches

Today, September 8, 2017 started and sort of ended with mini pity parties for me. We had a speaker this morning and I needed to go to the office ‘annex’. For some reason transportation decided they needed to get me to my 8:45 meeting at 7:30. Never going to understand that.

I was accepting of it and took along things to do for an hour. I am getting used to the indignities of the state subsidized transportation system.

After all, I am ‘handicapped’ and ‘elderly’. (You know I find that hysterical; don’t you?)

I was okay with it until my colleagues started to cluck their tongues and make a fuss over the absurdity of it all. Apologies for not thinking to offer well ahead of time and promises to do better. I was chastised for not asking by half the room. Then I had to fight the impulse to cry.

Not sure what upset me. It could have been being reminded it is not fair, whatever that means. It could have been their willingness to help. It could have been being reminded I am now different. Maybe a combination.

Whatever it was, sometimes it just smacks me (you, too?) between the eyes. Believe it or not, I am often able to forget I am now handicapped/disabled/impaired/whatever. Other times….I am sitting by myself an hour and a half early and people feel sorry for me and I feel sorry for myself and that is all she wrote.

The rest of the work day went great. Busy and sort of productive. Of course, I had to get a ‘seeing eye colleague’ to read a particularly blurry fax to me, but that was not a problem. People help.

(Of course this was the same colleague who was making the cracks about allowing the one, ‘blind’ staff member to cut the baby shower cake we had for another colleague! News flash: I could not cut equal pieces when I could see! Bringing to mind a corruption of an old joke: “Doctor, if you fix my vision, will I be able to cut a straight line?….Funny, I couldn’t do it before!” Da dum dum!)

And fixing eyes brings me to the second letdown of the day. I – and I believe others – have been thinking lampalizumab was a slam dunk. It was going to go breezing through the phase 3 trials and help to cure the world. Did not happen. Lampalizumab failed to show a statistically significant effect as compared to sham and the one trial has been terminated.

I looked all over the web trying for specific information and all I found was the press release repeated by about eight, different services. Not sure what happened and I don’t believe they know what happened. Here’s one version of the press release from BusinessWire.com.

Not that I am anyone you should listen to, but I would recommend not giving up yet. They still need to further analyze the data. It is possible they got a split just as they did the last time. Maybe 75% of the samples were non responders but the other 25% responded with a 40% slowing of the degeneration. 0 + 0 + 0 + 40 divided by 4 is 10. An average of 10% would not meet criteria but the 40% would.

Just wait and see. Some days have bad patches, yes, but they often are just that, patches. In the big picture, we are doing okay. Keep on keepin’ on.

written September 8th, 2017

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Recent Advances in AMD

One more very rainy day. Could be worse. We could be in Texas or Louisiana or Florida or on one of a dozen plus islands in the Caribbean. Definitely could be worse. [Lin/Linda: or Georgia.]

No hip hop class Monday evening because of the holiday. No class last evening because it was thundering and ‘lightning -ing -ing’. Can’t have yoga outside in those conditions.

Consequently, I have already started with a raging case of cabin fever….and I even worked seven hour days yesterday and today! What the hey?!?! Activity junkie here. Jonesing for my activity fix. Pitiful.

Good, bad or indifferent, when I am bored and frustrated I research. Then I write. I am always amazed at all of the research happening on macular degeneration.

Found an article that summarized a fair amount of the work that is going on. This time the Italians made the contribution. Doctors from Milan and Verona wrote Recent advances in the management of dry age-related macular degeneration: a review.

The authors broke down the research into methods of attack. The first area mentioned was nutritional supplements and the AREDS research. Since we have gone over that ad nauseuam, I am going to just mention it and move on. AREDS. ARED2 . Mentioned. Moving on.

Anti-inflammatory agents were next. The first one mentioned was Iluvien. Iluvien is a treatment for diabetic macular edema. It might also be helpful for AMD but the part I want to point out is the delivery system. Iluvien is injected once every three years!

Available in the UK and Germany as of 2014 and FDA approved that same year, Iluvien is delivered in a teeny, tiny little tube that is inserted into the back of the eye through injection with a very thin needle. As I said, the medication is delivered over the next three years. No additional shots.

Now I have not seen any references to this delivery system being considered for Anti-VEGF shots, but personally I would say it holds some intriguing possibilities. Cut the number of shots from 36 in three years to 1? That would have real appeal to me!

I believe I mentioned POT. That is POT4. It is a C4 inhibitor. Zumira and Eculizumab are C5 inhibitors. Once again they are picking a variety of complement factors to target. I believe this is just more evidence we are going to need genetic testing before treatment in the near future.

I also see it as evidence we may require combo drug treatments. If my genotype in regards to complement factors is as bad as I think it is, we may just get one, rogue factor under control before I am bit in the butt by another!

We have talked extensively about lamp stuff. Remember the real pronunciation of the word is more like “Lamp! Uh,Liz,you mab?”. Of course, you don’t need the question mark. I will, however, probably say it with that inflection forever. Thinking about breaking Elizabeth’s light is the only way I seem to be able to remember lampalizumab!

Plenty of other things mentioned but this is getting long. To be continued.

written September 8th, 2o17

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So Confused!

I am confused! Not exactly Earth-shattering news, huh? Anyway, I might, maybe, should withdraw what I said about ‘lamp stuff’ being available early 2018. I really am not sure.

My BIG retinologist (Dr. Carl Regillo, Wills Eye Hospital) told me he was thinking of starting me on lampalizumab at my next appointment, which is December, 2017. I heard it. I am going blind, not deaf. We know it would not be straight phase 3 because phase 3 enrollment closed sometime ago. I assumed phase 4 which would have opened it up to just about everyone everywhere. However, articles Lin has found – and I will go over – suggested that is not the case.

I went back to clinical trials.gov for some info. The id number for the study is this: NCT02247479. The study series started September, 2014. That would be phase 1. The date for final data collection for phase 3 is December, 2017 with data analysis and publication by December, 2018.

Now technically, if sites are going to roll immediately into a phase 3b, 3/4 or even a limited 4, I could be in line to have shots in December. Might have a lot to do with who my doctor is. Other people might have to wait. I might have to wait. No clue. [Lin/Linda: we have some clues since she wrote this that are at the end of the page.]

So, there it is. As far as I heard from my doctor, he was thinking about getting me on lampalizumab as early as December 2017. As far as the published articles are saying, we are looking at early 2019. My guess would be to split the difference, early fall, 2018 according to my ‘crystal ball’. Why, because Hoffmann-LaRoche, the parent company, has big bucks tied up in the research and is probably chomping at the bit to make an even bigger profit.

I am a cynic, so shoot me. I sort of think I was born cynical. Either way, my prediction is just that, a prediction. Don’t hold me to it.

All I can say right now is wait and see what happens. “Tune in in December for the next exciting installment of ‘Sue in the Land of the Visually Impaired!’ Will the Wizard try to slow her sight loss? Will he succeed? Will he try to help other citizens of the Land? Stay tuned here in December to find out!”

Sorry I assumed. We all know about assuming… and if you don’t it is ‘to assume will make an ass out of u and me’. Cute, huh? I probably just failed to factor in who my doctor is, access to all of the good stuff and all, because I know I heard him say it. I don’t hallucinate…all that much.

Which leaves me with exactly no space to go over the article Lin sent me. Don’t worry. It is a three-day holiday weekend. I will have lots of time to write other pages. What? Did you hear that? That was the sound of Lin groaning in Georgia…😎 Bye!

Lin/Linda here: Yes, I am groaning but not for the reason Sue originally thought.  When I searched clinicaltrials.gov for the study that she referred to above, ie. NCT02247479, I came up with 2 studies, one with that number with the information that Sue shared above.  The second one has the study number NCT02745119.  The title of the second one is “Long-Term Safety of Lampalizumab Intravitreal (ITV) Injections in Participants With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OMASPECT)” and it says it is phase 3 & is now recruiting and ending in October 2019. Maybe this is how she will be getting the ‘lamp stuff’??

written September 2nd, 2017 Continue reading “So Confused!”

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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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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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Snips & Snails & Puppy Dog Tails

Snips and snails and puppy dog tails are supposed to be what little boys are made of. However, now it appears we girls are made of snips also!

Just when I had decided I am not appropriate for ‘lamp stuff’ (lampalizumab) because I do not have the complement factor I (CFI) at risk allele, Lin informed me the snips ArcticDX tested for are not the same ones as in the study! I may be saying I don’t qualify because I don’t have ‘fruit’ but Arctic tested for oranges and the researchers tested for apples. Apparently all ‘fruit’ was not created equal. My CFI test that was fine may not really have tested what should have been tested if I want to make a decision about the study. I am so confused! [Sue talks about CFI & lampalizumab in pages I Want to Be a Mutant and I Am Not a Mutant.]

So what in Hades am I talking about? See above. The part about being confused. Let us delve further into this mystery.

A snip is actually SNP (it is pronounced snip). That is a Single Nucleotide Polymorphism. SNPs are tiny, little parts of genes. They are a variation in the spelling of our genetic code. Clear as mud, right?

Let us try again. The alphabet of genetics is made up of four letters: A, C, G,and T. Each of them is a nucleotide. Vary the order of the nucleotides on an allele and you can get any one of a variety of characteristics being expressed. Life in all of its diversity is written with a four- letter alphabet.

Sometimes Nature doesn’t spell too well. Sometimes she gets sloppy and copies a C for an A or whatever. These spelling errors do not cause disease but they can affect how the cell will function. They can also predict a response to certain drugs.

Spelling errors or SNPs are very common. According to my source, the Genetics Home Reference again, any one of us can happily harbor 10 million SNPs. However, even with that number of errors, Mom Nature still earns top grades in spelling. 10 million letters in error is a drop in the bucket when you consider how many letters were written for each of us.

We have gone from chromosomes to genes to alleles to SNPs. We are getting smaller and more specific as we go. Pages to paragraphs to words to letters. The SNPs are letters in error in the book of Life. Apparently the genetic testing I had found no spelling errors at the top of a paragraph while the researchers found spelling errors at the bottom of the paragraph. These bottom of the paragraph spelling errors caused the fantastic response to ‘lamp stuff’.

Looking at the perfect spelling of words at the top of the paragraph cannot tell me if I harbor those magic mistakes at the bottom. I am back to where I was. Indecisive as to what to do once again.

written July 30, 2017 Continue reading “Snips & Snails & Puppy Dog Tails”

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