In 2012, nearly one million Americans with diabetes were diagnosed with a lower extremity ulcer, and failure of these wounds to heal resulted in more than 75,000 lower extremity amputations. Valitor, Inc. is developing protein-polymer therapeutics to overcome the micro vascular consequences of diabetic wound healing. We designed our therapy to complement the standard practice of diabetic ulcer management and to reduce the costly serial effort required for debridement and clinical observation of these slowly healing wounds. Our patented technology is a bio conjugation process that enables us tether Sonic hedgehog (Shh), an important angiogenic factor, to linear chains of hyaluronic acid (HyA) at defined Shh:HyA ratios (i.e., valency). In Phase I of this project, we verified that Shh valency correlated with enhanced Shh-induced cellular functions, including downstream angiogenic signaling, which were substantially unregulated relative to equimolar concentrations of unconjugated Shh. We further demonstrated that after treatment with multivalent Shh conjugates (mvShh), full- thickness excisional wounds in db/db diabetic mice exhibited significantly greater neovascular density and faster closure times compared to wounds treated with unconjugated Shh or vehicle controls. Our overall goal during Phase II is to build on these promising proof-of-mechanism results by completing the lead optimization process and to advance mvShh to as a candidate for pre-clinical studies.

Public Health Relevance

In 2012, nearly one million Americans with diabetes were diagnosed with a chronic lower extremity ulcer, and these patients generate over $34 billion per year in related health care costs. Valitor, Inc. is developing an advanced therapeutic to accelerate healing in diabetic wounds, offsetting the high cost of treatment by encouraging neovascularization and improving blood supply in the wound bed. The overall goal of our Phase II project is to determine the molecular parameters of our therapy that generate the greatest therapeutic effect and to advance our technology toward clinical translation as a drug product.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AR062418-03
Application #
8843788
Study Section
Special Emphasis Panel (ZRG1-IMST-M (13))
Program Officer
Tseng, Hung H
Project Start
2012-01-01
Project End
2016-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
3
Fiscal Year
2015
Total Cost
$782,937
Indirect Cost
Name
Valitor, Inc.
Department
Type
DUNS #
965203222
City
Moraga
State
CA
Country
United States
Zip Code
94556
Holstlaw, Taylor A; Mahomed, Mavish; Brier, Livia W et al. (2017) Biopolymer Molecular Weight Can Modulate the Wound Healing Efficacy of Multivalent Sonic Hedgehog-Hyaluronic Acid Conjugates. Biomacromolecules 18:2350-2359