Anatomy of the Eye

http://www.mdsupport.org/anatomy.html

My Acetazolamide Case Study

I decided to do my own replication of the University College London acetazolamide case study (for more information, see my 2/15 post). This is not something to be entered in to on a whim. Acetazolamide is a hard core drug and I had to get blood work done regularly to monitor potassium levels and red blood cell count among other things. It has some very scary possible side effects including bone marrow stopping the production of red blood cells. It is a diuretic and it is important to monitor kidney function. So, one must commit to regular blood work. As an aside, I wish someone would attach a statistical measure to possible side effects. Then, it would be easier to make educated decisions. For example, if there is some extreme side effect, it would be helpful to know if 5% or 46% people in the clinical trial experienced it. Okay, I am off that soap box for now.

I started my dosing at 250 mg. on April 15th. I slowly ramped up to 500 mg. Then, I went to 1000 mg. for one month. I noticed colors looked brighter. I also had an improvement in my fields. I doubted if anything; other than increased color vision, was happening until I got off the drug. Then I realized that, indeed, it had helped. One would expect it to help the clarity of vision if I had any residual CME.

But, I also noticed an increase in my ability to find things. Do not get me wrong, I was still quite impaired. But, I did not run in to things in my own home. My shins had no bruises and I could wear skirts without looking like I was married to an abusive little person. I did not collide with door jambs. I could find most anything I needed independently. Still, I doubted my improvement. Now, that I am off the medication and have regressed, I notice that it was helpful in ways one would not expect if it simply resolved CME.

So, why did I discontinue using the drug? Well, I felt like absolute…..crud. At first, the 1000 mg dosing was fine. Besides having pins and needles in my extremities, being a little more tired than usual and everything tasting like metal, life was good. Then I started to become very fatigued. Getting out of bed in the morning became an act of will. If I did not have responsibilities, I probably would have spent the day in sweat pants (always my data point for a major case of the blahs). I also started having, shall we use a nice medical euphemism and say “gastrointestinal distress" on an all too regular basis.

So, better vision is not so useful when you feel awful. But, it does make me relatively optimistic about the potential of the Brimonidine Tartrate implant being developed by Allergan. For more information see the post from 4/20.

I think back to everything I have tried, from acupuncture to stem cell implants. Glaucoma drugs to microcurrent……there always seems to be a bit of efficacy to each. I think of microcurrent’s basis in sending an electrical current to the retina. Then, I see the implantable chip which generates electricity and stimulates the retina. Acupuncture is also an electrical process. So, there are some interesting parallels. My fields responded to acetazolamide. If it could be delivered locally, then we would have a more realistic therapeutic option. But, the devil is always in the details.

Now it is time to soldier on and be grateful for the desire to do so. An old friend called me, he is in his late thirties, a single dad and dying of a rare disease for which not ONE clinical trial has been conducted. So, we are relatively blessed compared to many. But, it is only human to lose sight of that when one is losing sight.

Muller Cells and RP

Scientists at Schepens, at Harvard, have discovered that Muller cells within our own retinas may have the capacity to turn in to various types of cells. According to this study, these cells have the possible potential of healing diseased retinas.

Why wouldn’t our bodies have the potential to heal themselves in this context? The human body is a miracle. A mundane miracle, but a miracle all the same.

http://www.schepens.harvard.edu/press_releases/march_24_2008.html

Fetal RPE Transplantation

Dr. Norman Radtke is doing RPE transplantation again. When I researched this procedure three years ago, he and his team were transplanting one sheet of fetal retinal pigment epithelial cells (RPE) in to the diseased retinas of people with RP and ARMD. He is now doing transplants with two sheets of cells, both neural and RPE cells. He has some recent case study data on his site.

If you go to the “clinical trials” section of this informative website, you will find information on the trial. He also has a section entitled “outside trials” as well as “trial bulletins”. Both are excellent resources for keeping up with the latest in retinal research, regardless of who is funding it. The “bulletins” section is one I find particularly notable.

http://www.rvrc.com/_drradtke.cfm

I did find some published work by Dr. Radtke on this procedure.

This article was published in 2004, and reflects the results when transplanting one sheet of fetal RPE cells.

http://www.ncbi.nlm.nih.gov/pubmed/15302656?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Information from 2002:

http://www.ncbi.nlm.nih.gov/pubmed/11931789?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

From 1999:

http://lib.bioinfo.pl/meid:112531

A Swedish rabbit study on "full thickness implant", which I believe may be both the RPE and neural retina layers.

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ArtikelNr=27472&Ausgabe=226339&ProduktNr=224269

Swedish pigs:

http://www.ncbi.nlm.nih.gov/pubmed/17072635?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
An 2002 overview of retinal transplantation:

http://www.djo.harvard.edu/site.php?url=/physicians/oa/379


I keep an eye on Steve Wynn, Las Vegas casino developer and gazillionaire, since he has RP and is one of the wealthiest people on the planet. In the blogosphere, there are numerous references to a "government approved experimental eye surgery" he had done in May of 2007 at Johns Hopkins. So, I tried to find any trials at Wilmer (Johns Hopkins) that are recruiting RP patients to see if I could make an educated guess as to which procedure he had done. I did not have much success. But, I will keep searching. According to the articles in the blogosphere (always suspect), he disclosed this surgery plan to his dealers on the eve of a union vote. They still unionized, but the information was made public. If you believe what you read, anyway.

Obviously, there are numerous ethical concerns when using fetal retinal tissue from aborted babies. Someone, I believe it may have been Mark Twain, stated something along the lines of, "Ethics are the luxury of the well fed." In other words, it is easy to extol lofty ideals and virtue when in a position of relative ease. The real test comes when "the rubber hits the road" and life becomes more challenging.

My personal opinion is, until you have navigated a busy intersection with a toilet paper roll encircling each eye and a stick, then you do not get an opinion. Okay, maybe you can have one. But, do not express it. At least, not around me, unless you come bearing dark chocolate and red wine. :)

Gene Therapy and RP

This is old news at this point, but I just have not found the time to write about it. Below is the article published in the New England Journal of Medicine regarding the recent gene therapy trial for LCA, a severe, early-onset form of RP.

http://content.nejm.org/cgi/content/full/NEJMoa0802268

There have been press releases issued to major news outlets. You can see the media coverage at the FFB website:

http://www.blindness.org/

It is worth the time to read the academic article. While it is difficult for a layman to understand all of the jargon, it gives a realistic picture of the actual results achieved.

Yes, it is very exciting. But, it is the result of, at least in the study published above, one person's improvement in one aspect of vision, contrast sensitivity. Apparently there is the study above as well as another one using a different set of three adults. This is the only published peer reviewed article I have been able to locate in PubMed (thanks for the share, G.). And, as all of the scientific types are quick to remind us RPers, one person's experience does not usually mean much and we should not invest too much time in being hopeful. Unless it is gene therapy, apparently.

I suppose I must be missing something. It certainly would not be the first time. Maybe the other study, which I cannot locate, had better results.

This is the first gene therapy trial, to my knowledge, done for a condition which is not fatal. I have to admit, I am floored the FDA approved gene therapy for a non-lethal condition. The exciting thing about this trial, based on the little I know about gene therapy, is no one had "adverse events", like dying, from the viral vector used.

A vector is a virus used to carry the normal copy of the gene to the target gene. The tricky part is using a virus that is not harmful to humans. In other (non RP related) gene therapy trials in the past, people have died from immune reactions resulting from the virus. This may be worth the risk to someone dying of a fatal condition. There is also the risk of the replacement gene not just going to the target area and inserting itself in other cells, leading to cancers.

However, by some miracle, these scientists actually were able to get this trial approved in this country for a disease that is not killing people. So, in the scientific community, that must make them rock stars. I am not talking some bubble gum boy band either. More like Keith Richards, able to defy the odds and astonish medical professionals time and time again.

Aging rock star jokes aside, It seems like there are multiple standards at work. Again, I am sure I am missing something. But, take our UCL acetazolamide case study. That is a case of one person having improvements in contrast vision. However, there were no press releases, no buzz or continued funding. Granted, her gains were not nearly as dramatic as the gains of the subject in this study.

But, the results obtained by one young person in the study are very encouraging to me. The increases in his ability to detect contrast are undeniable and unlikely to be explained away. The fact that the dogs who have received the same procedure, eight years ago, have maintained their gains is even more encouraging. And, this is gene therapy's first barbecue for RP in humans. This was just to test safety, and that anyone had any benefit at the most conservative dosing level is encouraging.

My personal belief is gene therapy may be able to help me one day maintain the results of a stem cell procedure. I think it holds an enormous amount of potential for young people who are newly diagnosed and identified. Hopefully the incredibly brave young people who participated in this study will have more improvement and stable general health.

The "subjects" are courageous, pioneering and inspiring. With all of the things I have tried, gene therapy would still terrify me, regardless of who was doing it. Kudos to the researchers as well. Firstly, for getting results. Secondly, for managing to get a trial with this amount of inherent risk done in this country. It has no doubt been a long, laborious road and I look forward to more good news.