# Treatment and prevention of osteoarthritis with an intra-articular disease-modifying regenerative therapy

> **NIH NIH R44** · REGENOSINE INC · 2021 · $860,384

## Abstract

Abstract
Nearly one in every ten Americans, and one in every three over the age of 65 years, suffers from osteoarthritis
(OA), a degenerative joint disorder that causes progressive cartilage loss. Current therapeutic options include
physical and occupational therapy, acupuncture, medication, intraarticular injection, and surgery. As total joint
surgery (arthroplasty) is costly and has a maximum lifetime of 15 years before requiring even more expensive
and risky revision surgery, OA intervention strategies generally retain patients on the least invasive methods for
as long as possible to delay the need for arthroplasty. However, the limited relief offered by palliative therapeutic
options such as exercise, anti-inflammatory medications (ibuprofen, glucocorticoids), narcotics (opioids), and
injections (hyaluronic acid, corticosteroids) impose a drawn-out period of suffering for OA patients to endure
chronic pain from cartilage destruction, inflammation, and other pathological damages associated with the
disease. Such approaches provide only symptomatic pain relief, and are not disease-modifying interventions.
Although the pathogenesis of OA remains incompletely understood, we have discovered that adenosine, acting
at its A2a receptor (A2aR), is a critical autocrine homeostatic factor that maintains chondrocyte and cartilage
balance. Regenosine is developing Lipo-Ade, a first-in-class liposomal adenosine product in a
proprietary, novel formulation for effective, prolonged treatment and for regenerating cartilage in joints
in patients with established OA. We have demonstrated that use of liposomes as a mechanism to encapsulate
the short-lived adenosine and its delivery into the intraarticular space enables the bioactive compound to promote
cartilage regeneration, stop the progression and reverse the pathology of OA. For this Direct to Phase II project,
Regenosine will continue to develop and test Lipo-Ade as an optimal OA treatment formulation in preparation for
initiating our clinical trials by undertaking four specific aims: 1) conducting studies to define release kinetics and
measure primary metabolites in synovial fluid and plasma, 2) performing a large animal proof-of-principal/bridge
study to evaluate the safety and efficacy of Lipo-Ade in pain and joint structural change in dogs with OA, 3)
characterizing an optimal, stable formulation, determining the chemistry, manufacturing, and controls (CMC) of
liposomes, and undertaking the manufacturing of a pilot scale batch, and 4) conducting Investigational New Drug
(IND) enabling pharmacokinetic and toxicology studies of the Lipo-Ade to satisfy requirements set by the US
FDA. These assessments will validate the safety, efficacy, and feasibility of Lipo-Ade to usher the technology
towards commercial application. Quality control standards such as shelf-life, sterility, batch-to-batch variation,
etc. in the manufacturing process will be addressed, and more importantly the ability of Lipo-Ade to reduce ...

## Key facts

- **NIH application ID:** 10256397
- **Project number:** 1R44AR078691-01A1
- **Recipient organization:** REGENOSINE INC
- **Principal Investigator:** Siddhesh Angle
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $860,384
- **Award type:** 1
- **Project period:** 2021-09-16 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10256397

## Citation

> US National Institutes of Health, RePORTER application 10256397, Treatment and prevention of osteoarthritis with an intra-articular disease-modifying regenerative therapy (1R44AR078691-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10256397. Licensed CC0.

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