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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Studying the Study

Lin found the paper discussing results from the phase 2 study of lampalizumab. It is a little dense but I will try to pre-digest it a bit for you. [Lin/Linda: we’ve been calling it “lamp stuf”.]

The study design itself was somewhat basic. There were two independent variables and two controls or shams. Independent variables are the things the researchers are manipulating. In this case it was two dosage schedules. Shots of the drug were given every month and every other month.

Controls, or sham treatment groups, were given shots on the same schedules. However, their shots did not contain lampalizumab. They just thought they did.

Overall, when the every month dosage of lampalizumab people were compared to the every month fake treatment people (sham condition), their rate of degeneration was slowed by a fifth. That is where the 20% number comes from.

However, when the researchers looked at their raw scores, they made a discovery. Some of the subjects absolutely rocked it! They were showing decreases of 44% in rate of deterioration. Others did not differ at all from the controls. Their eyes just continued to get worse at the usual rate. What the hey?

Thinking the difference might be genetic, the researchers thought about which genes to consider. They ended up with the complement factor I at-risk allele as a possible suspect.

An allele is half a gene pair. Genes come in pairs; remember? One from Mom and one from Dad. Alleles can be matched or mismatched. Terms are homozygotes and heterozygotes, but that’s not important in this case. It wasn’t important to the researchers either. They decided to look at people with one and two ‘bad’ alleles of complement factor I.

When they put everyone with good CFI alleles in one pile and everyone with at least one bad one in another pile, they made another discovery. It was the people with the bad CFI alleles who had responded to the lampalizumab. There appeared to be something about that gene that interacted with the lampalizumab in a way that slowed things down.

Looking back at their numbers, the researchers decided all of the ‘work’ done in the initial, whole group was done by the bad CFI allele people. There was an overall difference of 20%; right? But remember we are talking arithmetic averages here. If half of your group ‘improves’ by 40% but the rest of the group improves by 0% when you add them together and divide by 2, you get 20%. 20% is sort of misleading. No research subject showed a 20% rate decrease. They were either at somewhere around 44% or somewhere around 0%.

There are some things that need to be further studied. The number of subjects was not large and they need to replicate things with lots more people, for example. However, for right now the takeaway message for us is this: as suspected, AMD is looking like not one disease but a family of diseases. It is created by several different genetic flaws. The lampalizumab phase 2 study results suggest this drug will only be good for the AMD ‘family member’ that is caused by complement factor I at-risk allele. Those of us – like me – who do not have bad CFI alleles will have to wait for another breakthrough.

Those of you with CFI at-risk allele can rejoice! It looks as if they have found the first real TREATMENT and it is for you! Congratulations! We are all happy for you and want to follow you very soon.

If you really want to look at the scientific paper from the study, click here.

Continue reading “Studying the Study”

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Piles of Articles

Long, holiday weekend. I am on the second day of four and have gotten pretty much nothing done. Oh, well. Procrastination is us.

Be that as it may, Happy Fourth of July whenever you may be!

Part of the ‘straightening up’ task for me is going through piles of articles I have found interesting and printed out. That word is actually PILES.

Just rediscovered one – Update on Genetics and Age-Related Macular Degeneration by Jerome Dunaierf – that has some good stuff in it. Did you know people with a parent with AMD have DOUBLE the risk of getting the disease? Make sure the kids get their eye exams!

Jerome talks about the complement immune system and does a nice job – much clearer and nowhere near as fanciful – in describing how the ‘friendly fire’ bit works. He shared the proteins that activate the complement system have been found around drusen. (Maybe a demented garbage men analogy would be better? Coming for the trash but hauling away the house?)

Jerome also talks about the ARMS2/HTRA genes. Enticing and mysterious those. No true clue what they do but we with AMD often have certain variants of them.

Other genes that seem to be somehow in the mix include genes that code for collagen formation, cholesterol formation and cell signaling. You might not realize it but the chemical ‘chatter’ going on in our bodies is deafening! Eavesdrop on that and we could intervene in amazing ways.

Jerome agrees with me lampalizumab will open up a HUGE market for genetic testing. (Probably the reason I kinda like Jerome). He shared it is now possible to sequence an entire human genome in a few days. The cost? About $1,000.

Wow. Have your code read and know exactly which drug is going to work on you. How far in the future before genetic sequencing becomes a requirement for getting health insurance? Ethical nightmare that.

And a little filler here: Pubmed published an abstract on a meta analysis of 10 trials about the risks and benefits of aspirin. Bottom line was this: aspirin can keep those of us with cardiovascular problems alive. Proven. Aspirin might, maybe, could have a negative effect on your AMD. The authors, Small, Garabetian, and Shava decided most of us would want to be alive. Their advice was to take your aspirin.

OK. A few more things off the pile. Time to wander off to something else. Maybe some housework. Gasp!

I am staying home from yoga today. Self diagnosis of rotator cuff tendinitis. Doctor’s appointment next week by which time I will not only have diagnosed but also treated myself!

My yogini is digging out a ‘no arms’ practice she found so I can try that tomorrow. Movement continues to be important to – and for! – me. Where there is a will, there often is a way.

That is what is happening here. Hope you are all doing well. Bye! Continue reading “Piles of Articles”

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I Am Not a Mutant

This continues where page I Want to Be a Mutant ends.

I stand corrected. The genetic testing we had done by ArcticDx DID screen for complement factor I. I did not remember correctly. Mea culpa. I was in error.

Now the problem becomes this: I don’t have it. Everything else – OK, almost everything else – has one or two stars next to it. Next to complement factor I is a negative sign.

Unless I am also misinterpreting that, I would be a non-responder to ‘lamp stuff’. I guess someone else gets to be Storm. I am apparently not a mutant.

Not sure if that is good news or bad news. Reasonably sure being part of the lampalizumab study would keep me out of the stem cell study. I have always wanted the stem cells. I am also not excited about having a needle in my eye every month . Remember when I was talking about primal fears? One of them is bodily integrity. That is one of my biggies.

On the other hand, the stem cell study is taking forever to get off the ground. I could be effectively blind before they get their stuff together.

‘Tis a dilemma. Not sure why Regillo said he wants me on lampalizumab without knowing if I would be a responder. Not sure how much people without complement factor I actually responded. Not thinking it was much. Maybe he is just being a scientist and looking to experiment. I would not mind except for the needle part.

I really am not as brave as you wet folks; not at all. And that is especially true when I suspect I will get no benefit from it.

That said, you people who have had genetic testing, check your charts. The way Lin and I are reading them, the gene you are looking at is CFI, fourth from the bottom. If you have little stars, you should be a responder to lampalizumab. Take the chart to your doctor and inquire if I am accurate. Remember I have been wrong before, so check it out.

Of course, since ‘lamp stuff’ is only for slowing GA, you people with early AMD or wet AMD, won’t be candidates for it either. However, knowledge is power. If you have the gene and do progress to GA, you can respond quickly to get the right treatment.

You who have not had a genetic screening, hold on a bit. This is the first treatment for GA available and it is showing what looks like a relatively large difference in effectiveness across genotypes. I suspect insurance companies will start paying for genetic testing out of self-defense. [Lin/Linda here: Medicare HAS approved the ArcticDX testing.] I could not find frequency of the I allele quoted anywhere (and my eyes were crossing trying to read the genetics info, so I quit). However, I found the frequency of some other alleles associated with AMD to be about one in three. With two chances out of three the injections will not be effective in any given person, insurance companies will pretty much insist on genetic testing in the very near future. Meaning, my dears, they pay!

And that is that. I intend to have a talk with my local retinologist in August and Regillo in December. Those of you with research capabilities, keep an eye out for the phase 3 study journal article. I would like to read it.

And the journey continues. Continue reading “I Am Not a Mutant”

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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!] Continue reading “I Want to Be a Mutant”

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Not Created Equal

We heard from a reader who has vitelliform macular dystrophy. I had never heard of it. Therefore you can image my surprise when I picked up an article I had downloaded last week and – guess what! – the article talked about vitelliform dystrophy! Sometimes the synchronicity in the Universe is scary.

Anyway, it appears the Universe has declared we are to learn about vitelliform dystrophy. Here we go!

I have discovered all macular diseases are not created equal. There are dozens of them and researchers are discovering more on a regular basis.

Vitelliform dystrophy may look like age-related macular degeneration and act like macular degeneration but it is not macular degeneration. (Don’t worry. We are not throwing you out of the group!)

Vitelliform dystrophy is a pattern dystrophy. They are so called because the damage tends to ‘draw’ things on the retina. For example, one manifestation of the disease looks like a butterfly (photo to the right is a fundus photograph of butterfly pattern).

Vitelliform 2 is called Best disease. This is not because it is the best disease to have nor is it because Dr. Best hijacked the disease and named it for himself. It is because the disease comes as a result of a mutation on the BEST1 gene. (Apparently that means we all have BEST genes and there are at least two of them. How about that.)

Best disease is a pattern dystrophy because – all together now! – it makes a PATTERN on your retina. The pattern is a sunny-side-up egg. The yolk is centered on the fovea.

One of the nice things about Best disease is you may never know you have it.  According to the Hereditary Ocular Disease site 7 to 9 percent of those with Best disease are asymptomatic. Others may experience vision loss but recover most of their function. A much smaller percentage may proceed to neovascularization and serious loss. Of course, the older we get the better chance we have of having some really serious problems. And by the way, children can have this one.

That is because, once again, it is genetic. Best disease is an autosomal dominant condition. That means it is on a body-forming chromosome – not the chromosome that has the x or the y and makes you a boy or a girl.  It is also dominant and can express itself whether or not its partner gene wants it to. You only need one of these babies to be in trouble.

Of course there are all sorts of things that may or will affect whether or not this gene does actually express. However, this is not a place to discuss epigenetics. Nor am I the one to explain THAT baby! Suffice it to say, you should warn everyone you are related to by blood that it has expressed in the family and they need to have regular eye exams.

Like AMD there is absolutely no treatment and no cure. (I get so tired of typing that). If you have Best disease and progress to CNV you may profit from shots.

And that, my dears, is that. Continue reading “Not Created Equal”

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Hindsight is 20/20

Good evening! How are you all?

Lin has noticed I seem to have written soooo many pages they are overwhelming and confusing some people. She feels this is particularly true for some of the newbies who probably feel like they have walked in on the (boring and confusing) middle of a movie. [Lin/Linda: to be clear, those are Sue’s words! ::grin::]

Understood. Some of you are back in the shock and doom phrase and I am talking about getting newspapers on your phones and other trivial matters. Who wants to hear about that sort of thing while your world is unraveling?

In the interest of pointing you towards something that might actually be helpful, Lin is republishing some earlier pages for your attention and discussion. And I – always helpful – am going to add to the confusion by writing another page!😘

This page will have a catchy title thanks to Lin, but right now I am going to call it “What I know now that I wish I had known a year and a half ago”.

First, you are not going everything black and dark blind.

It is not good but neither is it quite that bad. You are losing central vision. Things will not be good for anywhere from about 15 to 60 degrees of arc. Since normal visual fields are 170 or so degrees of arc, you have the potential to lose about a third of your vision. Not anything to cheer about but better than 100%.

You may not be doomed to progress to end stage AMD.

About 15% of patients become ‘wet’. About 15% progress to geographic atrophy. That means you – starting out with drusen and a diagnosis of early AMD – have a 85% chance of dodging the proverbial bullet for end stage AMD. You may very well not get as bad as I am and a year and a half after my second eye went to hell, I am still functional. [Lin/Linda: a person can have both wet AMD and geographic atrophy in the same eye.  I don’t what that does to the %, if anything.]

You did not cause this.

Yes, AMD is caused but it was not caused by anything you did or did not do. The causes are in your genes. This is a heritable disease. There are dozens if not hundreds of genes that are being investigated to try to figure out how AMD is created. It appears AMD may just be the result of a genetic ‘perfect storm’ and there is no one to blame.

There may come a time you are seeing things.

I saw some odd stuff when my brain was working overtime to assign meaning to the faulty images my eyes were sending it. You are not psychotic (I hope you are not psychotic). This is Charles Bonnet Syndrome. When your brain gives up trying to assign meaning to false signals you will stop seeing weird ‘stuff’. In the meantime, enjoy the fantasy.

Point number last: There is an amazing amount of hope for treatment and eventually a cure for AMD.

Research is going on everyday. New discoveries are announced with regularity. The medical community is hot on the trail of something that will arrest the progression and may even reverse this disease. All we have to do is hold on.

OK. Those were my biggie when I first lost my second eye. What are you worried about? Please share and we can discuss it. Continue reading “Hindsight is 20/20”

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