Brian S. McKay, PhD, Director of Research at the Southwest Center for Age Related Eye Diseases, talks about a study with a Parkinson’s drug that may help delay if not prevent age-related macular degeneration.
If you would outline your study for me?
McKay: Our study has been going after the pigmentation pathway, the way in which the study governs your eye color or your hair color and your skin color. And we know that hair color, eye color, skin color kind of relates to the incidence of age-related macular degeneration the number one cause of blindness. By going after that pathway, our thought was if we can increase lighter colored people, increase that activity, we might be able to protect them from AMD and that is what my lab has been concentrated on since about the year 2000.
What exactly does that mean when you’re talking about lighter colored people?
McKay: It’s not only races, there is a racial component to it obviously, but it’s not only race. In the white population, we have people that clearly have darker hair and they have darker skin.
Who is in your clinical trial and why?
McKay: It’s largely going to be the white population and the population over the age of 75 to 80 years old. Because these people are the most likely to benefit from anything that we find, but they’re also most likely to have the disease and to actually develop the disease, so we can see if we can prevent it. If they already have AMD and they have wet AMD in one eye, the likelihood of the second eye converting, it’s called conversion, is very high over a very short period of time, like two years. So if we catch somebody with one eye with wet, we’re really sure the second eye is going to go soon, so we can treat those people and see if we can block that. At the same time we can see if we can reduce how many injections they need in the eye that was already being treated. So these people seem like the prime candidates, because they’re already going to their ophthalmologist, they already have a problem, we already know the path they’re on. So if we can alter that path, it seems like the best risk to reward ratio.
Let’s backtrack a little bit as to why the light haired, light eyed, light skinned people would respond and would need the Levodopa?
McKay: So there’s a pathway that actually governs retinal development and retinal survival as we age. That pathway, we’ve discovered, is absent in people with albinism, people with albinism are actually pretty much born blind, most people don’t realize that. The center of high acuity vision, the macula that you’re using to see me, doesn’t fully develop in people with albinism. They don’t get that ever and it can’t really be fixed. So the thing that is lost in age-related macular degeneration is never given if you failed the pigment at all, you don’t get one. In the older people they have this pathway, but in white people it’s less active. If we treat them to increase the activity of that pathway we think we can stop or prevent AMD.
Because dark haired, dark skin, dark eyed people already have it.
McKay: They have it and it’s at a higher extent, so the pathway is more active. The activity of pathway is reflected by your hair color and your eye color. So in dark haired, dark skinned people that pathway is more active than it is in light haired, blond haired, blue eyed people unfortunately.
So is it a deficiency in light skin, light hair, light eyed people or is it just an excess in dark?
McKay: I don’t know how you would characterize it, that puts a judgment term on it that I wouldn’t be willing to do. I would say there’s less, that doesn’t mean it’s deficient. I’m shorter, that doesn’t mean I’m deficient in height. Because I’m not seven feet tall doesn’t mean there’s something wrong. Or as the seven footer that I watched last night have an excellent game is he excessively tall. So it’s hard for me to put a judgment on that. I can tell you it’s lower activity.
So what happens when you give people the L-dopa in your trial?
McKay: It should increase the activity of that pathway, which will increase the retinal pigment epithelial which is the brown cells in your eye, increase the activity of that pathway and they take care of and protect the retina that’s on top of them. That’s their job normally. And in blue hair, blue eyed, blond people there’s less pigment. So in dark haired people, when I take donor eyes and I look at them, I can actually tell you what hair color those people are mostly, and what skin color they were just by looking at the back of the eye.
So by giving the patients in the trial L-dopa then what happens, how is it working?
McKay: It will increase the activity of that pathway and that should over time protect their retina. And it gives off two growth factors, two neurotrophic factors that are very specific in the eye. One is pigment epithelial derived factor, PEDF. It is the most potent neurotrophic factor in your body and it is governed specifically by this pathway. So, when we turn on the pathway with L-dopa, we increase PEDF secretion which supports and nourishes the retina. It also does one thing that we really like it to do, it turns off that vascular epithelial growth factor, and this pathway turns that one off. That is actually treatment for wet AMD is to turn that pathway off. So if we take somebody who has wet AMD and we give them L-dopa we should be turning off the pathway that governs the growth of new blood vessels. We should be keeping that from happening. We should be able to stop that.
What kind of results have you seen so far?
McKay: It’s just starting. I can tell you from a large paper study, looking at it that it looks like we can both prevent and delay AMD in people that take L-dopa for movement disorders, it was a big effect. We both reduce the risk of ever developing the disease and so the incidence was lower and we also showed that if you were taking L-dopa for a movement disorder you developed AMD much later. Rather than at 71 years old, which is kind of the average for everybody in the country, you didn’t get it until you are about 80, so we can push that back.
You are pretty excited about the potential for this trial?
McKay: I am, I think that we can win; I think we can cure this disease. I think we can prevent it and I think that we can actually keep people from having all those injections. I think we can keep that from happening.
Are you recruiting?
McKay: That has to go through Dr. Robert W. Snyder, MD, PhD, there are four clinicians in town right here in Tucson that are actively working on this. I can’t, I have a Ph.D. I don’t have a license to practice medicine. But I can kind of oversee the whole thing. I can look at the data; I can see whether or not we’re doing it correctly. There are some aspects of this that are not just trivial. Like when do you give the L-dopa, do you give it before they go to bed or do you give it in the morning? And the eye is diurnal, it has these variations that change night and day. So when we give the drug may dictate whether we get a response, I’m watching that.
Are you recruiting patients yet?
McKay: Yes he is. The recruitment is active as of I believe January, we have three versions of clinical trials approved by the FDA.
Redundant trials or different?
McKay: Slightly different in aims. One is to figure out what dose we should be giving people. Another is when; there are questions that are imbedded into this so they’re kind of overlapping but not necessarily. The third one I think is for the conversion one. So, they already have wet AMD, we know that, it’s in one eye now we’re looking for conversion in the second eye so that’s a different trial as well.
So it will be the one with Howard Morrow?
McKay: That would be the one; he should really want to do that one, that’s the one he should really want to be in.
So if people are interested, do they have to be local?
McKay: Right now the only thing we’re doing is right here, under Dr. Snyder’s trials and Robert Snyder, MD, PhD, initial clinic, he’s overseeing all of the clinical management of it.
So the best way for people to find out and try to get in a trial is to go to Clinicaltrials.gov or to call Dr. Schneider?
McKay: Both because anything at Clinicaltrials.gov is going to end up on Schneider’s desk anyway. Either way, he’s a good guy.
What haven’t I asked you about the trial or anything you would like people to know?
McKay: I think the clinical trial is exciting I think it’s going to happen and I think we’re going to cure this. I think we have another disease we can get rid of.
END OF INTERVIEW
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Brian S. McKay, PhD
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