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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 following video provides a summary of Catalyst for a Cure research and an update on research progress by the team during the past year.
Dr. Jeffrey L. Goldberg: We’ve identified, over the first few years of the Catalyst for a Cure Biomarker Initiative, and made a lot of progress figuring out: What should we be looking for in glaucoma patients? What are the things that go wrong? What’s happening in the biology of glaucoma that we could use to detect patients earlier in the disease or to figure out who’s getting worse and who’s doing okay? Those are the most important questions that we really need to ask in glaucoma.
This year has been an enormous step forward for us in developing the tools that we will use to transition our laboratory studies into human studies. In particular, our two world-class lead engineering collaborators Dr. Alfredo Dubra and Dr. Vivek Srinivasan have been building the actual instruments that will be used to peer into patients’ eyes and image their retinas and optic nerves at a level of detail never before seen.
The progress we’ve made on building these tools this year is going to set us up for the coming year to start an intensive program of human subjects testing to really put these biomarkers to the test.
Dr. Andrew Huberman: A biomarker can mean many different things, and when we set out to find a biomarker, we discussed whether or not this was going to be some way of imaging into the eye and seeing whether or not the retina was sick, whether or not it was going to be based on a blood draw, or some other measure.
At the same time, we realized pretty quickly that there were some basic questions about biology of glaucoma that needed to be answered in order to better understand what would be a useful biomarker.
To summarize what we found, there’s been a long-standing issue in the field of whether or not specific types of ganglion cells are being lost in glaucoma. Why would that be useful information? There are about 20 different types of ganglion cells and each one signals something different to the brain about the visual world. Some like motion, some tell your brain about colors, et cetera.
For example, if it turned out that you were losing ganglion cells that responded to motion early in the disease, then you can imagine designing visual field tests that would detect motion in particular and tell us whether or not people were losing certain kinds of ganglion cells long before pressure increases or holes in their visual field would show up.
That would be wonderful because you could intervene with treatments very early, and you could imagine monitoring the disease progression using essentially noninvasive measures. You also would have a target for eventually developing a cure and halt the progress of neurodegeneration by going after those cells, in particular, and try to save them.
What we discovered was that was in fact there are a certain group of cells in the retina, retinal ganglion cells, and a particular group of those ganglion cells which we call OFF cells. Those are the cells that respond whenever the room gets dimmer or there are decrements in light; those are the ones that appear to be vulnerable at early stages of the disease and those are also the ones that are going to die first.
What does that mean? That means one can devise visual field tests that specifically probe the health and integrity of the OFF cells, so that’s what we’re doing now. We think that in the end, the biomarkers are going to be something like a visual field test or perhaps direct imaging of the OFF cells in the inner retina. We’re chasing both of those leads with full force and we’re very excited about the progress.
Dr. Vivek Srinivasan: Work in my laboratory is attempting to build upon the results in Dr. Huberman’s laboratory to use his finding of specific early changes in one layer of the retina in early glaucoma and to develop biomarkers for those changes based on the energy usage and microvasculature in that layer.
These biomarkers can then be applied in glaucoma suspects or glaucoma patients to detect disease earlier as well as to detect progression much earlier at a stage where it can be prevented through appropriate treatments.
Dr. Alfredo Dubra: The work in Vivek’s lab is very synergistic and collaborative with ours and one of the main examples is the fact that since we can now see blood vessels and capillaries noninvasively in humans, we can now take advantage of some of the really advanced mathematical tools developed by Vivek and his team to actually quantify those blood vessels and have the shape in three dimensions.
This way, we can actually monitor and detect those really subtle changes that we’re really targeting so that we can not only diagnose glaucoma earlier, but we hope to be able to adjust the treatment very precisely for the people who are being treated for glaucoma to minimize the vision loss that takes place.
Dr. Huberman: I think it’s safe to say that within the next two or three years we will have something that doctors can use to evaluate patients to determine how quickly the disease is progressing, whether or not there’s glaucoma in the first place, and what to do about it. Much better than current techniques, all based on the work that was done in the first three years of the Catalyst for a Cure.
Dr. Goldberg: I’m often asked: 'why is it taking so long to find a cure for glaucoma?' We are making enormous progress. In fact, so much of the progress that we’re making in laboratories, including mine, is on developing neuroprotective therapies that can protect the retina from degeneration, regenerate optic nerve fibers all the way back to their targets in the brain, and even replace damaged retinal ganglion cells with self-therapies that completely rebuild the optic nerve.
We are making enormous progress, but how do we accelerate that into the clinic? This Biomarker Initiative dovetails perfectly with the research we’re doing in regenerative ophthalmology because it’s going to give us the tools to translate what we’re doing in the laboratory into human subjects trials.
If we can’t measure the positive effects of these candidate therapies, we can’t hope to transition them into human subjects trials. This Catalyst for a Cure Biomarker Initiative is really catalyzing leaps forward in our ability to move candidate therapies out of the laboratory and into the clinic.
Last reviewed on January 06, 2017