macular degeneration, macular, diagnosis lampalizumab – My Macular Degeneration Journey/Journal

Keeping Our Eyes Open

Greetings from Pennsylvania where it is 90°F in the shade. I was just puppy lifeguarding for about an hour. Now they are sleeping. All that swimming and fighting with your sister is tough on a puppygirl!

Speaking of the weather, I need to remind you, if you are having a heat wave like we are, please make sure you are drinking enough. Be sure you are able to get to someplace cool. This is especially true if the power goes out and your air conditioning goes off. People die of the heat every year.

I should be doing other things; I know. I’m not. Having four days a week off takes away a lot of the urgency. Besides, I would have to go inside to use the CCTV or to clean and I don’t want to go in. I am one of those weird people who loves this weather.

So you are stuck with me and a hodgepodge of news. First of all, I discovered they published the ‘official’ lampalizumab results in JAMA Ophthalmology this month. It is still June, so, yes, this month. Of course, the bottom line has not changed: it did not work. They are perplexed as to why they found an interaction between a certain genotype and the treatment when they ran the phase 2 data. It was not there when they ran larger numbers in phase 3.

Of course, the researchers are still crunching data. They are also planning on running whole genome sequences on the subjects to see if their genetic make-ups shed any light on what went wrong. Maybe suggest some new use for “lamp stuff”. Not to be too cynical about this, but this treatment cost plenty to develop and was supposed to be an amazing cash cow for Roche. Might as well see if there is a use for it somewhere.

I found a plan for a research review published by staff in the genetic medicine department at Newcastle University. They are planning to gather all the research they can find on photobiomodulation and dry AMD and see what they discover. This might be the first salvo in a battle to get the Lumithera machine approved in the UK.

Apparently, they are not sure exactly how the thing works. The section on the science behind it is headed “How the intervention might work.” (I always like magic myself!?) What they think is there is some sort of interaction with the mitochondrial that leads to a reduction of oxidative stress. Maybe. Like I said, magic.

I am not finding an end date for their research review and meta-analysis. I cannot, however, believe it will be too long. Maybe a year or so. Maybe more.

Coming across “the pond” I found an article about Lumithera presenting at ARVO in Seattle. The research LIGHTSITE 1 is promising.

I then went to clinical trials.gov and found a 2017 study that was identified as phase “not applicable”. Ok. Considering we are all lifetime learners… I found a flowchart on how to identify a device that would be applicable for a clinical trial but I did not get very far. Either the government’s verbiage is obtuse or I am. Suffice it to say, it has something to do with not requiring phases. Why? You are actually asking ME?!?!

Anyway, the 2017 research ran an ‘n’ [number of participants] of something like 30. Pretty small. Not sure if that will be good enough for the FDA even with all the European data. You people with early stage AMD, keep your eyes open. This one just may be for you!

Written 6/30/2018

Next: When the Going Gets Tough…

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No Respect

Anybody remember Rodney Dangerfield?   His catchphrase was “I get no respect”.

Although I have at times thought that dry AMD was being treated as the proverbial red-headed stepchild, I have always tried to talk myself out of that attitude. The people with wet have real problems. They are one bleed away from blindness. It makes sense they would work for a cure for them first.

However, I finally found someone who at least in part shares my concern. Philip Rosenfeld  down at Bascom-Palmer feels the same way. He doesn’t think dry AMD gets any respect either!

Rosenfeld talked about how all of the clinical research seems to have been focused on wet AMD. However, the truth of the matter is good responders to Anti-VEGF and dry AMD folks alike just keep getting blinder. Rosenfeld remarked how atrophy after ‘eye shots’ and dry AMD has become the most common causes of vision loss from AMD.

Rosenfeld – bless him! – goes on to say the effects of dry AMD are  ‘underappreciated’. Go, Philip! You tell ’em, buddy!

The functional vision loss associated with macular atrophy can be devastating. Okay, so we don’t have these dramatic crises like the wet people but that doesn’t mean we are not suffering. Dry AMD folks have feelings, too.

In addition Rosenfeld goes on to say the proof that dry AMD – and I quote – “never got the respect it deserved” can be found in the International Classification of Disease codes. Dry AMD was seen as so unimportant that there were  no subclassifications.  That is sort of like saying cancer without assigning a type or a stage.  Does the patient have stage 1 skin cancer and we remove the offending spot in the dermatology office or is it stage 4 bone cancer?  Doesn’t matter. It is just cancer.

Once again Rosenfeld notes the societal impact slowing macular atrophy will have. He remarked that vision loss has real impact on quality of life and it is much more than reading letters on an eye chart.

For example, I could not read the forms given to me at the veterinarian’s yesterday. I asked for help. (In case you did not notice, I am trying to be a good role model here. Do ask for help!) Multiple the three minutes the clerk took to help me by 1,000. How about 10,000? That is 500 man hours the people who are helping us could be doing other things!  Good grief.

Rosenfeld then went on to talk about how it has finally dawned on some researchers that we really may be having – and causing – some real problems.  Enter the studies they are now trying to slow the progress of dry AMD.

Lampalizumab looked promising but died in the stretch. Horse racing idiom there.

APL2 is getting a lot of hype. Just the same, there are concerns. As we saw, some people who saw the PowerPoint presentation on the drug  decided “this horse is lame”. (Coming from my heritage, I prefer “that dog don’t hunt” but the idea is the same and I really did not want to mix my references ?) [Sue wrote about this in her page Another $64,000 Question.]

Rosenfeld opined that failure of APL2 to produce any substantive functional vision differences may lead to the question of when to intervene with dry AMD. Rosenfeld seemed to suggest early intervention may be better than late.

Me? I am with Rosenfeld. We know where this stuff leads. There is no question of the potential endpoint. I say nip it in the bud! Treat early!

But who am I? Just somebody with a disease that gets no respect.

Written April 1st, 2018 Continue reading “No Respect”

Home Again

Greetings! Home again and it seems as if we were never gone. That nearly two weeks just flew! The only way I can be sure we were gone is I am freezing! There is about a 40 degree difference in temperature between the Caribbean and home. If I ever disappear you are all welcome to come looking for me. You can start with Costa Rica.?

Because a WiFi connection was something like 79 cents per minute from the ship, I have been very out of touch. I just did a little research and it appears the second half of the Lampalizumab study also failed in phase 3. That was the Chroma study. Spectri was the failure announced back in September. Or maybe it was the other way around. Anyway, it appears they both failed to meet the desired endpoint in the study. In an article in Healio.com Jeffrey Heier said they have collected a great deal of information they still have to analyze. They are hoping to be able to use this information to better understand geographic atrophy and also to develop new ways of fighting it.

Personally I am still perplexed as to why lampalizumab did so incredibly well in phase 2 trials but failed in phase 3. According to what I have read three-quarters of treatments that pass phase 2 pass phase 3 with no problems. Tis a mystery. Maybe the folks at Genetech can find the answer to that one.

I have already written a bit on BEST disease. That is the AMD disease that is not really AMD. I know at least one of our readers has BEST. October 25th News Medical published the results of a “disease in a dish” study done at Columbia and the University of Rochester. They took skin cells from people with BEST disease and regressed them to become pluripotent stem cells. They then took these stem cells and ‘nudged’ them into becoming retinal pigment epithelial cells.

As expected, these RPE cells growing in a dish (meaning they had no outside influences on them) did the same ‘bad things’ that happen in an eye with BEST disease. Once again this is a strong indication the problem is in the genetic coding.

So far this is old news, but the rest of it is not. The researchers found they could actually reverse early damage through gene therapy. They introduce healthy copies of the faulty gene using viral vectors. Once their codes were corrected, the cells started to recover and to perform like healthy RPEs.

Ready for prime time? Not hardly. This research is still happening in a petri dish. However, the rate at which this sort of research is progressing is startling and if I had to take a shot in the dark, I would say clinical trials may only be a few years away.

Hang in there and stay optimistic. We are making progress daily. Me? I have to make progress on vacation laundry!

written November 11th, 2017 Continue reading “Home Again”

“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!””

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

Continue reading “Bad Patches”

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

Continue reading “Recent Advances in AMD”

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!”

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

Continue reading “Research: Dry & Wet AMD”

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”

Thank a Mouse

This page is just me being inquisitive. If you are not up for me trying to figure out biochemistry, you might want to skip this page.

Looking at the medications they are using for wet AMD and the new treatment for dry AMD, lampalizumab, I noticed something.  Most of the generic names end in -zumab. What the hey? What is that????

To begin with, I discovered there are two suffixes, -ximab and -zumab.  Wikipedia actually has a whole list of medical suffixes but I am concerned about two right now. Those are the ones related to drugs for AMD. Suffice it to know that every suffix means something.  -olol for example will always mean a beta blocker. Of the two I am interested in: – ximab always stands for a chimeric agent that responds to more than one antigen;  and -zumab always stands for a humanized antibody.

See what I mean about just skipping this page?

Chimeric.  Now I knew what a chimera is. A chimera is a single organism composed of cells that should have made up multiple organisms. The organism  is made of genetically different cells. According to MedicineNet human chimeras were discovered when it was noted some people have two different blood types. The generally accepted ways a human chimera is formed are for nonidentical twins to share blood in utero or for one to absorb the other.

Once again according to Wikipedia, chimera proteins are produced through the joining of two or more genes that originally coded for two different proteins. The properties of the new derive from each of its ‘parents’. Naturally occurring chimera are often found in cancer cells; thus, it would appear, the wisdom of using manufactured chimera proteins to battle cancer (a genetic version of fighting fire with fire). Chimeric cancer cells happen because of random genetic mutation. Chimeric proteins in drugs happen by design. Read genetic engineering.

Forging ahead here, every drug ending in -zumab is a ‘humanized protein’. And, no, that does not mean it is kinder and gentler. It means that the base protein used in the drug probably came from a mouse. Generations of lab mice have had the very stuff of their being manipulated in the search for ways to improve our health. Think kinder thoughts about the little devils.

Because – actually two becauses – there are a lot of similarities between mouse DNA and human DNA, we can use mouse as the frame for our designer drugs. Because some of their proteins are foreign to us and would cause an allergic reaction, the proteins have to be ‘humanized’. Potentially offending sequences are cut out and replaced by sequences found in humans.

The idea is to produce proteins that will get into a sequence of reactions and somehow change it. In dry AMD lampalizumab weakens the immune reaction. Wet AMD drugs intercept the SOS message being sent by the eye. That is the one saying the eye needs more ‘supplies’ and new ‘supply routes’ (blood vessels) should be built.

So that is the answer to that burning question (you really were dying to know; I know). If you are taking a drug ending in -ximab or -zumab,  you are the beneficiary of altered protein sequences. Be grateful. Thank a mouse.

written July 1st, 2017

Continue reading “Thank a Mouse”

I Want to Be a Mutant

I want to be a mutant. Oh, not like the X-Men although it might be cool to be Storm. I want to be a mutant because those are the people who respond the best to lampalizumab.

A friend emailed me an Associated Press piece entitled Drug shows progress against vision-robbing disease in seniors. Although this was the first time I have heard this, according to the article, ‘lamp stuff’ doesn’t do a bit better in people with the specific gene mutation, it does a LOT better!

I had heard that lampalizumab produced a 20% regression in lesion progression. That, folks, appears to be an average.

Those with the complement factor I risk allele actually had a 44% reduction in geographic atrophy progression. Wow!

To me, this is the first BIG indication genetic testing and AMD treatment have to be closely associated. I really do NOT want to be poked in the eye with a needle every month if the treatment won’t do any good. Likewise, I will be more amenable to said needle poking if I know I have the gene and I can slow my vision loss by nearly half. Not to mention how insurance companies would respond if they knew they could save money by eliminating non-responders from the pool.

Now, you need to remember all of the hard sciences are not my forte, but it seems to me complement factor I is a molecule that helps to trigger the action of the immune system. Remember all that stuff about whether or not AMD is an autoimmune disorder? It appears complement factor I is able to slow down some aspects of immunity that are running amok and attacking the good guys as well as the bad. Once again the theory appears to be our sight is being wiped out by friendly fire.

Musing here a moment, I have a very strong immune system. Never had mumps or chickenpox. Only had one form of the measles. In the 50s and 60s when I was small, kids got those things all of the time. Once more, I was the odd one. But what if my great immunity is not the result of a strength but actually of a weakness? To wit, I have an immune system with bad brakes. That is a thought. After vanquishing all the bad germs, it turned on itself. Put that with a strong family history of RA, another autoimmune disorder and it makes you wonder. Things that make you say Hmmmm….

Anyway, lampalizumab tightens loose brakes on immune reaction in those who have the complement factor I risk allele. It keeps the immune system from running wild and reduces the rate of damage about 44% in geographic atrophy.

I don’t believe the genetic testing we were given for trial measured the complement factor I risk allele. However, I should suspect changing the genes they highlight may not be that big a job. I also suspect making that adjustment would be a big moneymaker (This is America, after all).

So, next we should probably all find out if we are mutants. I have dibs on being Storm. Who wants to be Wolverine or Charles Xavier? [Can I be Wolverine? Love what he does with his nails!]

written June 28th, 2017

Continue reading “I Want to Be a Mutant”

Geez, It’s Dark in Here!

Back again. I don’t want to scrub the floor or score a test, soooo….a page!?

Still checking out short blurbs from Modern Retina. Rosenfeld reported that low-luminance visual acuity deficits are predictive of the rate of geographic atrophy (GA) progression. Low-luminance visual acuity is basically night vision.

Following up on this I discovered that back in 2008 Janet Sunness found GA patients who reported poor night vision were much more likely to go legally blind than their GA peers who could see better at night. These people made up the quarter of their GA patients (visual acuity of 20/50 or better) who became legally blind within four years.

I believe them but still have a couple of questions. Recovery time from being ‘blinded’ by bright light is forever for me. Leave me there and come back in an hour.

Night vision is not bad. I prefer to walk without a flashlight because I see better to navigate. How can that be considering I am one of those who became legally blind?

The study measured night vision by seeing how much could be read in low light conditions. Reading in low light, I am not so good. Maybe that is the difference.

Anyway, if you cannot afford a lot of fancy testing, seeing how much you can read at dusk may give you some idea of how bad things are going to get. Just what we want to know; right? How bad things can really be.

And in other news, inflammation remains a target for the AMD researchers. Lampalizumab, aka ‘lamp stuff’, blocks complementary factor D to help control the alternative complement pathway (that thing again!) and reduce retinal inflammation. ‘Lamp stuff’ is said to work with carriers of the complement factor I at risk allele. Considering​ Regillo wants to start poking needles in my eyes come 2018, I cannot help but wonder if I actually have that gene. I would hate to be poked in the eye every month to no good end.

Maybe I would rather use POT. ?That’s POT 4. POT4, aka APL 2, blocks all three pathways of complement action at the same time. They are looking to develop an intravitreous shot that would be very long-term. None of this four to six weeks business.

And talking about shots, I just lost the article somewhere in this mess (not domestic goddess material; remember?) but I also read a short article taking about a new, medication delivery system they are working on in the UK. This team has been working on developing a little, bitty molecule that can permeate the layers of the eye and deliver medication to the retina through daily eye drops and not monthly shots. Not only will the people getting the shots approve, but the NHS (National Health Service) will approve because it will cut the number of office visits way down. Save money. Ka ching! [Lin/Linda: never fear, I found the article, click here.]

So there you have a review of some of the articles I pulled off of Modern Retina. They have lots in the works. Some of it is promising and some proves not to be, but they are zeroing in on treatments (plural because with a condition caused by multiple genes I believe there will be multiple avenues of attack). We are getting closer to answers. There is hope. Continue reading “Geez, It’s Dark in Here!”

BIG News!

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

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

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

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

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

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

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

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

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

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

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

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

Continue reading “BIG News!”