Synergy in Action

Two Concurrent Catalyst Initiatives Push for a Glaucoma Cure — and More

If 2022 was a milestone year, with the launch of Glaucoma Research Foundation’s fourth Catalyst for a Cure initiative, 2023 is proving to be an equally important time of growing synergy in vision science.

While GRF’s latest consortium gains traction in its quest for insights into neurodegeneration, a second Catalyst team, at work since 2019, is speeding toward sight-restoring therapies. Along the way, the two teams are sharing discoveries and inspiring each other.

“This is an extraordinary moment in the history of glaucoma research,” says Tom Brunner, President and CEO for Glaucoma Research Foundation. “Thanks to our donors, for the first time, we have two groundbreaking Catalyst initiatives under way at once. That’s an exceptional level of ingenuity and collaboration, all focused on finding a cure for glaucoma, and more.”

Building on a Bold Foundation

Catalyst for a Cure is a cross-disciplinary, uniquely collaborative approach to discovery pioneered by GRF. Each Catalyst initiative (CFC for short) unites four brilliant scientists whose paths would likely never cross without funding that focusses them on a shared goal: a cure for glaucoma.

The two concurrent Catalyst consortiums (CFC3 and CFC4) are just the latest in a stream of collaborative innovation that began with the launch of CFC’s inaugural Catalyst for A Cure Biomarker Initiative in 2002. This breakthrough program, completed in 2012, redefined glaucoma as a neurodegenerative disease, in the same family as Alzheimer’s, opening the door for new therapeutic approaches and future discoveries.

Launched in 2012 and completed in 2018, the CFC Biomarker Initiative dug deeper into the science of retinal ganglion cells (RGCs), the specialized neurons that deteriorate with glaucoma. Scientists identified biological markers that could signal early changes that lead to vision loss, then tested their findings to develop potential new therapies. Their research has already resulted in at least two new clinical trials to protect vision.

CFC3: Saving and Restoring Vision

One of the two initiatives currently in progress is The Steven and Michele Kirsch Catalyst for a Cure Vision Restoration Initiative (CFC3).Launched in 2019 and currently funded through 2024, this consortium is looking for ways to preserve the optic nerve, independent of eye pressure. Where damage has already resulted in vision loss, the team seeks ways to repair or rebuild nerve tissue and restore sight.

“The main problem with glaucoma is that patients are at risk of losing vision, and many have already lost vision,” says Dr. Jeffrey L. Goldberg, MD, PhD, Professor and Chair of the Department of Ophthalmology at Stanford University School of Medicine and CFC3’s lead advisor. “With a focus on preventing or reversing RGC degeneration and restoring vision, this initiative has special relevance to current glaucoma patients.”

The CFC Vision Restoration Initiative has made enormous progress in identifying molecular pathways that lead to RGC degeneration and has identified genes and molecules that could prevent vision loss and promote the regrowth of retinal ganglion cells. “They have gotten excellent data in animal models and preclinical models,” says Dr. Goldberg.  “And they have made great strides working with stem cells, which are relevant to other diseases of the central nervous system.”

Although there is more discovery and validation to be done, CFC Vision Restoration Initiative has already prepared key findings for translation into human therapies. Dr. Goldberg is proud of the exceptional collaboration he’s seen among four scientists from seemingly unrelated fields.  And as a former member of the Biomarker Initiative (CFC2) himself, he is inspired by this team’s progress. “The CFC Vision Restoration Initiative’s work just reinforces my feeling that a cure will be coming,” he says. “They are accelerating toward candidate therapies faster than thought possible. Breakthroughs from their laboratories could move into humans over the next couple of years.”

CFC4: Preventing and Curing Neurodegeneration

Launched in July 2022 and currently funded through 2025, CFC4 — The Melza M. and Frank Theodore Barr Foundation Catalyst for a Cure Initiative to Prevent and Cure Neurodegeneration — pursues one of our most confounding medical challenges: how to prevent and cure diseases that, like glaucoma, Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS), occur when key cells in the central nervous system deteriorate and die.

The team’s lead advisor is Adriana Di Polo, PhD, Canada Research Chair for the University of Montreal’s Departments of Neuroscience and Ophthalmology and the 2019 winner of GRF’s prestigious Shaffer Prize. “Glaucoma shares several common features with other neurological disorders such as Alzheimer’s disease,” Dr. Di Polo says. “For example, aging is a major risk factor for developing either condition.” By exploring common signatures between these diseases, CFC Neurodegeneration Initiative aims to uncover novel therapies and cures that could be applied to glaucoma, Alzheimer’s, and other neurodegenerative conditions.

The CFC 4 Neurodegeneration scientists met for the first time in July 2022 to articulate a direction for their work and set milestones. “This first year has been a time for team members to get to know each other, to discuss strategies, resources, and protocols, and to start gathering data,” says Dr. Di Polo. The project is still so new, it’s difficult to predict when results might emerge, Dr. Di Polo adds. But she believes the team is moving in the right direction. “They have a clear plan of action, with concrete objectives and experiments that they are currently pursuing,” says Dr. Di Polo. “And they are already generating data comparing the transcriptomic profiles of non-neuronal cells in models of glaucoma, Alzheimer’s disease, and glioblastoma.”

Like CFC team members before them, CFC4 participants are extremely talented young scientists who have already shown great promise as leaders in fields as diverse as brain vascular biology, neuroinflammation, computational biology, and cancer neuroscience. As individuals, they bring unique and complementary skills and experience with multiple disease models and molecular strategies — a major strength for the team. “I would love to be a fly on the wall at their meetings to hear all the new ideas that emerge,” says Dr. Di Polo. “It will be thrilling to watch their progress and see how they evolve.”

Two Initiatives, One Mission: A World Without Glaucoma

Although CFC3 and CFC4 may appear to be on two disparate discovery tracks, their concurrent explorations promise to generate greater progress toward shared goals than either could produce alone. “The thing that really sets these two initiatives apart — and this is a unique advantage of the GRF approach — is that the two teams can share findings and inspiration where their areas of study overlap, generating synergy not possible in other research settings,” says GRF’s Tom Brunner.

Mechanisms are already in place for sharing between the two teams. CFC3 and CFC4 consortia members meet together twice a year, with their next meeting slated for August 2023. Between meetings, some scientists are now interacting and collaborating across CFC lines, “and I anticipate that this exchange will ramp up in the near future,” says CFC4 advisor Dr. Di Polo.

“It’s great to accelerate research by doing two projects in parallel rather than in serial fashion,” adds Dr. Goldberg, CFC3 Vision Restoration advisor. “The interactions are deeper and more fruitful. The science is even more amazing — and more fun for the scientists. Being able to share findings and learn from each other speeds the progress of both teams. And the faster we can successfully bring therapies to patients, the better.”

The greatest point of synergy between the two projects, Dr. Di Polo says, is their common mission to cure neurodegeneration and restore the function of critical cells, whether they affect vision, cognition, or another human function. “Together these two CFCs have the potential to reverse vision loss, change the landscape of neurodegenerative diseases, and bring new therapies to the clinic,” she adds. “Without the generous support of GRF donors as well as their constructive input and motivation, this work would not be possible. On behalf of our CFC teams and the scientific community, I would like to say thank you.”


Posted on December 12, 2023

Source: Glaucoma Research Foundation’s “Insight” donor newsletter, Fall 2023 edition