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Development of Nicotinamide-Riboside plus Pterostilbene as a Disease Modifying Osteoarthritis Therapeutic

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AR082748-01
Agency Tracking Number: R41AR082748
Amount: $283,071.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAMS
Solicitation Number: PA22-178
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-06-01
Award End Date (Contract End Date): 2024-05-31
Small Business Information
New York, NY 10013-2563
United States
DUNS: 079482547
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (888) 220-6436
Business Contact
Phone: (888) 220-6436
Research Institution
SAN DIEGO, CA 92161-0002
United States

 Domestic Nonprofit Research Organization

Osteoarthritis is a progressive joint disease that affects more than 32 million Americans and over 655 million
worldwide. OA is the leading cause for pain and disability in individuals over 65. Estimates place the annual US
economic burden of OA at $136.4 billion. OA care continues to rely on NSAIDS for symptomatic pain
management and joint replacement as a last-resort. Disease modifying OA therapies are currently unavailable.
Prevalence of OA is predicted to rapidly increase due to population aging and rise of obesity therefore
innovative approaches that slow or reverse OA progression and are a dire unmet need.
OA is a whole-joint disease featuring progressive loss of cartilage, dysregulated bone growth and chronic
synovial inflammation. Redox imbalance-induced oxidative damage and mitochondrial dysfunction instrumental
to OA pathology. NAD+, a Vitamin B3 metabolite occupies a pivotal role in cellular redox reactions,
mitochondrial function and is a required cofactor for sirtuins1-7. The Sirt1/Sirt3 axis has been shown to play a
protective role in OA on account of their ability to promote chondrocyte autophagy and survival. Both NAD+
levels and activity of Sirt1/3 decrease during chronic inflammation and decline with age, leading us to
hypothesize that concomitant elevation of NAD+ and Sirt1/3 activation may be a promising approach for
developing a disease-modifying OA treatment.With the overall goal to develop EH302 as a disease-modifying treatment, this Phase 1 STTR
application is a joint effort from Elysium Health and the laboratory of Dr. Ru Liu Bryan in the Division of
Rheumatology, Allergy and Immunology at UCSD. Elysium Health, co-founded by Dr. Leonard Guarente, a
pioneering researcher in the field of sirtuin biology, is a New York-based small business with a core focus on
NAD+ boosting and sirtuin activating products. The immediate objectives of this Phase 1 STTR are to
demonstrate proof-of-concept and feasibility of oral EH302 as OA treatment. In Aim 1 we will determine
efficacy and safety of EH302 in a rat model of trauma-induced Osteoarthritis. Major milestones will be
reduction of pain and protection from joint damage. Aim 2 will investigate tissue distribution of NR and PT
metabolites after oral EH302 intake using isotope-labeling and mass spectrometry. Based on promising pilot
data we expect that oral EH-302 will meet primary outcome milestones for reduction of pain and joint protection
demonstrating proof-of-concept and feasibility of development as an OA therapeutic.

* Information listed above is at the time of submission. *

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