Repairing the Extracellular Matrix:  Request for Proposals

Request for Applications

SENS Research Foundation is seeking applications for innovative approaches to repairing age-related extracellular matrix (ECM) damage, including but not limited to nonenzymatic or enzymatic crosslinks that accumulate aberrantly with age, such as specific advanced glycation endproduct (AGE) crosslinks, medial elastin calcification, shifts in collagen subtype, and fraying of elastin lamellae.

Applicants should clearly indicate the specific stable structural change in aging ECM that would be the research focus and explain how their proposed research would further progress toward therapies that directly remove, repair, or replace that target and the anticipated effects on health and function.

SENS Research Foundation was founded to catalyze progress in the “damage-repair” approach for medical intervention in degenerative aging, and we fund proposals that offer the potential to progress toward medical therapies specifically using this approach. “Damage-repair” interventions in this GlycoSENS program are those that directly remove, repair, replace, or render harmless one or more specific ECM lesions.

Successful applicants should focus on stable, structural, accumulating alterations to molecular and cellular structures over time, rather than unstable intermediates or reactive precursors. Applicants should explicitly address how their research topic qualifies as stable, accumulative structural damage, and how it contributes to age-relate health decline.

Applications that focus on modulate metabolic pathways as their primary approach will generally be unsuccessful. This means that small-molecule drug intervention applications are typically unsuccessful, as their mechanism of action typically involves inhibition or promotion of some targeted pathway of metabolism.

A successful “damage-repair” proposal will clearly lead toward direct removal or repair of some form of aging damage, which generally entails delivering some novel capacity that the organism does not intrinsically have as part of normal metabolism. Some representative examples of damage-repair approaches include the biotechnology startup company Revel Pharmaceuticals, spun out from Yale research originally funded by SRF, which is developing enzymes that cleave the AGE crosslink glucosepane in arterial collagen, and the startup Elastrin Therapeutics, which is working to develop nanoparticles that bind specifically to frayed elastin and locally deliver EDTA to decalcify aging medial elastin, based on work originally conducted at Clemson University.

The proposal should address the following areas:

  •  The specific stable structural lesion in aging ECM that will be the focus of the research
  • How the proposed research is expected to lead toward a therapeutic means to directly remove, repair, or replace said lesion.
  • An overview of the proposed approach and any supporting evidence
  • A plan for testing and validating the proposed approach
  • A description of the proposed budget, including personnel and materials, and requested years of funding
  • A timeline for completion
  • A description of expected outcomes and/or implications

Proposals should be submitted via Proposal Central by September 1st, 2023, using the following link:

https://proposalcentral.com/GrantOpportunities.asp?GMID=267

All proposals will be evaluated on the basis of scientific merit, practicality, therapeutic translatability, and budget.

We look forward to receiving your proposals and thank you in advance for your interest in this important cause of aging and diseases of aging.

A GlycoSENS Intro

Our bodies are comprised not only of cells, but of long-lived proteins that physically support those cells, create ordered tissue structures of them, and participate in their function. Such extracellular matrix (ECM) proteins are responsible for the elasticity of the artery wall, the transparency of the lens of the eye, and the high tensile strength of the ligaments, for example, as well as sustaining the function of our tissue stem cells and preventing cancerous cells from escaping their local environment to spread into other tissues.

Thus, for our tissues to function healthily, these ECM proteins must themselves maintain their proper structure over time. But many of these structural proteins are only recycled over the course of many decades, and others not at all. Over time, they become damaged — by abnormal cross-links; by mechanical wear and tear; by abnormal mineral deposits; and by other damage caused by the metabolic and physical forces they sustain in fulfilling their duties as part of a complex living organism.

One of the most well-understood ways that ECM damage drives age-related disease, debility, and death is the stiffening of the large arteries. Several kinds of damage to the aging arterial ECM cause the arteries to lose their elasticity over time, making them less able to cushion end-target organs like the kidneys and the brain from the cyclical hydraulic battering ram of the pulsing of the blood. Without this cushion, every heartbeat damages the structures that filter our blood, threatens the integrity of vessels in the brain, and threatens the eruption of a clotting eruption from atherosclerotic plaques, leaving us at increasing risk of strokes, kidney disease, and loss of regional connectivity in the brain. Targeting these various ECM lesions for removal, remediation, or repair thus holds enormous promise to prevent, delay, and begin to reverse a sweeping range of downstream dysfunction and ill-health.

About SENS Research Foundation

We fund innovative research at universities across the world, at our own Research Center in Mountain View, CA, and through investments in early-stage companies.

Our research emphasizes the application of regenerative medicine to age-related disease, with the intent of repairing underlying damage to the body’s tissues, cells, and molecules. Our goal is to help build the industry that will cure the diseases of aging.

Our outreach efforts include speaking engagements, conferences, and summits while providing general advocacy through newsletters, videos, educational programs, and social media. We strive to inform world policymakers, health professionals, and the general public about our damage-repair approach to treating, and curing, age-related disease.

Finally, SRF engages in educational work through our student program, SRF Education. SRF Education operates an undergraduate summer internship program, as well as a 10-month post-baccalaureate program, both of which place students and new researchers at the SRF Research Center and world-class institutions. The programs provide participants with guidance, mentorship, and materials grants for SENS-related research projects.

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