MTM Vision: Executive Summary

The Challenge: Vision Loss from Diabetic Retinal Disease (DRD)

Many of you know Mary Tyler Moore by her work as an actress and diabetes research advocate. Her professional persona was one of joy and optimism, yet very few people knew of the burden she carried due to her struggles with diabetes and its complications. To the outside world, she was a beautiful, happy, independent woman. Privately, diabetes and her near-blindness from diabetic retinal disease (DRD) stole her joy and autonomy.

Sadly, Mary’s story is not unique. Everyone with diabetes knows the fear of possible vision loss. Tens of millions of individuals worldwide suffer from blindness and vision-threatening retinal disease as a complication of type 1 or type 2 diabetes. DRD is, in fact, the leading cause of blindness in working-age adults worldwide, with more than 50 million people suffering from vision-threatening DRD globally.

Our Response: A Multi-Phase Initiative to Preserve and Restore Vision in People with Diabetes

Recent decades have given rise to great advances in retinal imaging technology, gene therapy, regeneration science, and the understanding of the neurologic component of DRD and the cellular and molecular basis for this disease. Thanks to these advances, there is hope that vision restoring treatments and new ways to prevent visual loss and blindness for people with diabetes are now within our reach. However, these breakthroughs require committed collaborations, access to specialized resources, and real-time data sharing between innovators across the spectrum of expertise. The Mary Tyler Moore Vision Initiative (MTM Vision) is establishing the enabling resources and collaborations, bringing cross-sector expertise together, and supporting the scientific programs needed to accelerate research and development of new therapies. Our ultimate goal is to create a world without vision loss from Diabetic Retinal Disease.

Our Roadmap: 

Phase 1 of MTM Vision provides critical-path resources to address three key barriers to accelerated progress:: 

1. You can’t solve a problem you haven’t defined. The current method of staging DRD is over 40 years old and includes only the visible vascular component of the disease. This approach has limited how we think about therapeutics development and care, and prevented us from achieving optimal outcomes. To accelerate advances to preserve and restore vision in people with diabetes, a staging system and severity scale that takes into account the full spectrum of disease and its impacts are needed. This must include visual function and quality of life, cellular and molecular origins of disease, and the pathophysiology of retinal nerve injury (in addition to the retinal vascular component of DRD).  Our first accelerator, therefore (which is on-going), is to update the Diabetic Retinal Disease Staging System and Severity Scale.

2. You can’t cure a human disease unless you can study the human condition. In order to study DRD in humans and accelerate progress, a resource of human retinal tissue and fluids is needed, that has been properly collected, characterized, and stored and is available to be shared, globally, with researchers willing to share their data in real-time. Our second accelerator is, therefore, a human eye tissue biorepository, established at the University of Michigan Kellogg Eye Center. The Mary Tyler Moore Ocular Biorepository and Resource Center is key to a cellular and molecular understanding of DRD and to identify molecular targets for potential new therapies, including in early-stage disease when there may be retinal physiologic and functional impairment without visible vascular disease on color retinal photographs. This will form a foundation for the global scientific efforts, across sectors, needed to accelerate translation of research into cures. 

3. You can’t judge success unless you know how to measure it.  There is need for consensus across industry, academia, and regulatory bodies around Clinical Endpoints and Biomarkers for DRD diagnosis, risk prediction, prognosis, and evidence of disease progression and therapeutic benefit, including those that incorporate the patient voice, test visual function, and assess retinal pathophysiology. Our third Phase One accelerator, therefore, is to lead a much needed Clinical Endpoints and Biomarker Identification and assessment process and to provide support for the validation of clinical endpoints that will be useful in accelerating new therapeutics development and optimizing clinical care. Valid metrics for evaluation will allow researchers to more effectively determine whether potential therapies are successful, and regulators to compare efficacy. By establishing consensus around and regulatory approval (FDA/EMA) of DRD endpoints and biomarkers, we will accelerate moving scientific advances from the research lab to benefits for the patient. 

Successes in our Phase 1 will help:

• Establish new indications for treatments in DRD, including in earlier stage disease

• Enable identification of new therapeutic targets at molecular and cellular level

• Inform new regulatory pathways for drug approvals

To realize the full value of our Phase 1 projects, we are establishing a cross-sector, pre-competitive consortium to provide members access to our unique biospecimen and data assets to support their relevant research efforts… thereby accelerating progress toward development and approval of new ways to preserve and restore vision in people with diabetes.

(See our “Milestones” document included later in this Program Book for summary of Phase 1 progress)

Phase 2 of MTM Vision will advance DRD diagnostic capabilities and support novel Therapeutics Targets Identification:

Phase 3 of the Mary Tyler Moore Vision Initiative will organize and support outcomes-driven, science with a mission programs designed to develop new methods to preserve and restore vision in people with diabetes, including programs that focus on methods to:

1. Arrest the pathologic progression of the vascular and neuronal disease of DRD and protect vascular integrity and neuronal function from further damage from diabetes.
2. Induce self-repair/regeneration of damaged retina to preserve and restore visual function.
3. Generate and implant a partial or full replacement retina in end-stage DRD with GMP generated neo-retina “patch” to restore visual function.

References

1.   Tomilo M, Ascani H, Mirel B, Magnone MC, Quinn CM, Karihaloo A, Duffin K, Patel UD, Kretzler M. Renal Pre-Competitive Consortium (RPC(2)): discovering therapeutic targets together. Drug discovery today. 2018;23(10):1695-9. Epub 2018/05/21. doi: 10.1016/j.drudis.2018.05.021. PubMed PMID: 29778696.

2.   Levine SR, Myers MG, Jr., Barunas R, Chang D, Dutta S, Maddess T, Liebmann JM, Sherman S, Eydelman M, Sun JK, Chambers W, Wickstrom K, Luhmann UFO, Pellinat M, Glassman A, Aiello LP, Markel DS, Gardner TW. Report from the 2022 Mary Tyler Moore Vision Initiative Diabetic Retinal Disease Clinical Endpoints Workshop. TVST. in press.

For more information, please e-mail S. Robert Levine, MD at srobertmd@mtmvisioninitiative.org

The Mary Tyler Moore Vision Initiative’s audacious goals are to preserve and restore vision in people with diabetes. It is a joint effort of The Mary Tyler Moore and S. Robert Levine, MD Charitable Foundation, The University of Michigan’s Elisabeth Weiser Caswell Diabetes Institute and Kellogg Eye Center, JDRF, and the Entertainment Industry Foundation (EIF)

Mary Tyler Moore Vision Initiative is a fund of the Entertainment Industry Foundation (EIF), a Charity Navigator Four-Star Charity that meets all 20 Better Business Bureau charity standards and carries the Candid Platinum Seal of Transparency.