Grant Award Details
Pre-IND Meeting with the FDA
Grant Application Details
- Pluripotent stem cell-derived chondrocytes for articular cartilage repair
We propose to develop a universal, off-the-shelf treatment for articular cartilage repair based on pluripotent stem cell (PSC)-derived chondrospheres
Area of Impact
The proposed therapy could treat the major cartilage lesions present in more than 10% of people under 50; which often result in pain and arthritis
Mechanism of Action
Untreated cartilage defects often lead to joint pain and degeneration over time, often requiring joint replacement. The proposed candidate is a universal cell therapy designed to generate new articular cartilage in these defects and interrupt the cycle of degeneration.
Unmet Medical Need
Approximately 10% of people under 50 have at least a single, high-grade defect in their knee cartilage; these lesions have a high probability of promoting subsequent degenerative processes, often resulting in arthritis. Currently, there are no effective treatments for altering this progression.
Major Proposed Activities
- Optimization of large-scale production, preservation and quality control of pluripotent stem cell-derived chondrocytes
- Conduct nonclinical safety and stability tests in small and large animal models
- Develop a draft clinical protocol and synopsis and conduct a successful pre-IND meeting
The work described in this proposal is designed to produce a universal treatment for articular cartilage lesions. If successfully validated, this cellular therapy will likely help reduce joint pain and reduce further degeneration of joints that leads to arthritis. The proposed treatment may be of major public benefit, as it would represent the first curative strategy for cartilage injury and subsequent degeneration, likely decreasing economic burden on the state and its people.
- Osteoarthritis Cartilage (2019) CaMKII inhibition in human primary and pluripotent stem cell-derived chondrocytes modulates effects of TGFbeta and BMP through SMAD signaling. (PubMed: 30205161)
- Nat Commun (2018) Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes. (PubMed: 30194383)
- Ann Rheum Dis (2018) Drug-induced modulation of gp130 signalling prevents articular cartilage degeneration and promotes repair. (PubMed: 29436471)
- Nat Cell Biol (2018) ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs. (PubMed: 29255171)
- JCI Insight (2017) Kappa opioid receptor signaling protects cartilage tissue against posttraumatic degeneration. (PubMed: 28097228)