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Video: Catalyst for a Cure 2014 Progress Report

The Catalyst for a Cure Biomarker Initiative funded by Glaucoma Research Foundation is a collaborative research effort designed to accelerate the pace of discovery toward better treatments and ultimately a cure for glaucoma.

The Catalyst for a Cure principal investigators are: Alfredo Dubra, PhD, Medical College of Wisconsin; Jeffrey Goldberg, MD, PhD, Shiley Eye Center, University of California San Diego; Andrew Huberman, PhD, University of California San Diego; and Vivek Srinivasan, PhD, University of California Davis.

Video transcript:

Jeffrey Goldberg, MD, PhD: The toughest part of diagnosing glaucoma is that in most patients it affects the peripheral vision, the edges of your vision, first, and the center of your vision very late in the disease. So most people who have glaucoma are probably walking around in the world today with no idea that their peripheral vision is a little less than it used to be. Worldwide, glaucoma is the leading cause of blindness, other than cataracts. We have no way for patients who have lost vision in glaucoma to restore that vision, to give them back vision that they’ve lost. Right now, all of our treatments, the best that they can do is try to slow the decline, or prevent the further loss of vision, but we have no way to bring vision back in glaucoma — and both in this country and worldwide that remains the leading, leading, un-met need in all of ophthalmology.

The Catalyst for a Cure team, my three colleagues and I, have been working together; it’s been a very exciting period and I think we all feel like we’ve made a lot of progress in new directions that none of us would have thought to go in without having been brought together by the Glaucoma Research Foundation.

We have two neurobiologists who are studying retinal ganglion cell and optic nerve biology — and that’s me and Andy Huberman — and we also have two optical imaging engineers with very different backgrounds — and that’s Vivek Srinivasan and Alf Dubra. And by bringing together people with really disparate, different sets of expertise, that’s another way that we hope to do something really novel, creative, and unique through this opportunity.

Andrew Huberman, PhD: Each of our labs uses a variety of techniques such as anatomy or imaging, or physiology, molecular biology and genetics but no two labs are exactly the same; so what’s really great about the Catalyst for a Cure initiative is that each lab is very expert in one or a few of those different techniques.

So for instance, two of the members of Catalyst for a Cure, Alf Dubra and Vivek Srinivasan, are both expert imagers and so they really developed a lot of new technology to image deep into the eye and into the brain to understand how neurons are organized. Jeff Goldberg is a clinician and also studies the biology of ganglion cells. My laboratory has essentially established itself for studying the biology of ganglion cells, in particular developing genetic methods and other methods for labeling and looking at specific sets of neurons in the eye, specifically retinal ganglion cells, which are the neurons, of course, that are disrupted in glaucoma.

The number of people with glaucoma is increasing all the time and so given how dependent humans are on vision to get around in our day-to-day lives, I think it’s absolutely crucial. This is one of the most important problems in visual neuroscience as a field, to be able to take basic research in the laboratory and translate it into useful treatments for patients — and glaucoma, I really believe, is the place to do that.

We know exactly which cell types are affected, and so we really need to figure out ways to monitor and treat those particular cell types. There are a lot of people out there that don’t have glaucoma yet and that we’d like to prevent from getting glaucoma, and to be able to detect the health status of ganglion cells is one important way to do that. Of course there a lot of people out there who already have glaucoma, and we need to inform their treatment regimens as well as decide whether or not there should be more aggressive treatments for glaucoma. This is an extremely important problem.

So biomarkers for glaucoma would be just wonderful to have for a couple of different reasons. The first is that typically we don’t know how actively to treat glaucoma, even in patients with very elevated pressures, because people vary in the extent to which they lose ganglion cells in response to pressure increases. At the same time some people are losing ganglion cells whose pressures are in normal range. So having a biomarker that could evaluate the health status of ganglion cells, independent of pressure or in conjunction with pressure, would be a terrific thing for monitoring treatment, deciding essentially how many rounds of treatment or how prolonged the treatment should be, for deciding whether or not a patient should undergo treatment or not. Most importantly, for being able to detect glaucoma in cases where people have not yet reported visual field loss and pressures are normal.

Vivek Srinivasan, PhD: Biomarkers are important in determining whether a drug is effective because it shows us whether the patient is getting better or not, and it’s important to have very sensitive biomarkers — biomarkers that are getting at the disease itself.

Current biomarkers that we have for glaucoma, intraocular pressure or visual field, are indirect measures at best; what’s really causing the disease is the loss of ganglion cell function. Our goal is to develop biomarkers that directly assess the function and metabolism of ganglion cells and these will be better able to distinguish successful drugs in clinical trials.

My group in particular is interested in developing metabolic signatures of disease. So what I mean by that is, metabolism is basically the housekeeping chemical processes that are going on in the cell. It’s very difficult to see metabolism from looking at the structure of cells, so we’re trying to find ways to interrogate the function of cells or find if cells are stressed or unhappy before you actually start to see some of these hallmark structural changes of disease that ophthalmologists use to diagnose disease and follow progression.

Alfredo Dubra, PhD: My lab has been focused on developing instrumentation to look at the retina on a microscopic scale, and it’s been pretty exciting because we’ve already discovered some new pathologies that we didn’t know were there, despite all previous studies both with microscopes and with patients. And we are now taking advantage of the different skills that we have in the consortium to try to interpret these and see how they evaluate the potential to be a biomarker of either progression or an early diagnostic tool.

What we are developing now are a really unique set of tools that are going to allow us to monitor the changes in the retina at the cellular scale over time in the same person; and we think that this is really going to have a transformative effect because it’s not only very powerful from the statistical point of view but it really is going to allow us to do experiments that were not possible before.

Every day, every month there are a lot of people who are being affected and we do appreciate that our mission is not something to answer in terms of scientific curiosity, but really is in terms of helping people out; so we appreciate the sense of urgency and we’re really betting very heavily on it.

Jeffrey Goldberg, MD, PhD: To my mind there’s no question, we will see new cures for glaucoma in our lifetime. We’re making a lot of progress as a field in understanding the basic underlying biology of what’s going wrong in patients with glaucoma. We’re making a lot of progress in how we measure glaucoma, including looking for newer, much better, biomarkers for glaucoma, for example through this Catalyst for a Cure collaboration. And there are a lot of treatments, or let’s say potential treatments, that are working wonderfully in preclinical models that are ready to make the leap to human testing, and some of these have begun to make that transition to bridge from the laboratory to human-patient testing.

But it’s going to be much easier to test more of them and really learn which ones are going to work, which ones are going to help patients, once we have better biomarkers — better ways of measuring the progression in this disease.

End transcript

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Last reviewed on October 29, 2017

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