A team of University of Pittsburgh researchers have identified the role of estrogen receptor-a (ERa) in osteoarthritis (OA), a debilitating and painful joint disease. Through enhancing ERa levels in damaged cartilage cells, treatment of OA may be possible.
Description
While there are multiple causes of OA, in OA affected joints both preserved (P-C) and severely damaged (D-C) cartilage is present in the affected joints, suggesting that OA is linked to distinct mechanical loads and not to changes in synovial fluids. RNA sequencing showed the estrogen receptor-1 (ESR1), a gene encoding ER?, is significantly downregulated in D-C when compared to P-C. Enhancing ER? levels may be a novel approach to treating osteoarthritis.
Applications
1. Osteoarthritis
2. Joint disease
3. Cartilage repair
Advantages
Osteoarthritis impacts over half a billion people globally and is a growing area of public health concern. There are no known therapies to halt or reverse the progression of the disease with current treatment focusing on the management of symptoms, adjustments in lifestyle and in rare cases, surgery.
Given the debilitating effects of OA, treatment remains a significant unmet need. This approach could reverse some of the cellular changes linked to OA with the potential to cure the condition.
Invention Readiness
Animal studies have shown the benefit of increasing ERa in reversing some of the damage from OA. Both damaged and preserved cartilage was harvested from the same OA knee joint in human samples. RNA sequencing showed significant reductions in ERa levels in D-C compared to P-C cells. Using animal knockout and knockin of ESR1 models the role of ERa in mediating chondrocyte response to mechanical loading was established. Knockin of ESR1 was shown to partially reverse the osteoarthritic phenotype of OA chondrocytes. This evidence of disease reversal highlights the potential therapeutic advantage of increasing ERa to treat OA. Studies have identified two potential compounds, RAD001 and Urolithin A that can significantly enhance the levels of ERa in chondrocytes.
IP Status
https://patents.google.com/patent/WO2023172608A2
