Repurposed biologic, Abatacept, which promotes new bone formation via T-cell modulation for the treatment of osteoporosis.
- Increases osteoblast activity to promote new bone formation unlike a bisphosphonate which limits bone loss.
- Offers a once monthly injection option compared to daily injection.
- Abatacept already FDA approved for rheumatoid arthritis.
The National Osteoporosis Foundation estimates that 10 million Americans have osteoporosis and another 34 million have low bone mass. The standard of care for osteoporosis is anti-resorptive therapy to prevent further breakdown and fractures. These treatments are usually administered after substantial bone loss has already occurred. Because bone breakdown and bone formation occur concurrently and because anti-resorptive therapies not only lower bone breakdown but simultaneously reduce new bone formation, it is almost impossible to restore bone mass to a normal, healthy level. In addition, the new bone that is formed may not be optimal due to the effects of the treatment and the micro-damage that occurs can accumulate and limit the maximum duration of use of the drug. There is one agent on the market that is capably of promoting new bone formation to rebuild bone mass, an anabolic parathyroid hormone (Forteo); however, there have been some issues with the therapeutic due to the need for daily injections for up to two years, waning efficacy over time, and the increased risk for certain cancers such as osteosarcoma.
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by chronic T-cell activation. T-cell costimulation inhibitors like Abatacept are increasingly used as therapeutic agents to suppress T-cell activation and ameliorate RA symptoms. Abatacept specifically suppresses costimulation of CD28, a molecule expressed on T cells which is required for T cell activation. Dr. Weitzmann has found that this suppression of CD28 costimulation due to Abatacept treatment can also act as a bone anabolic in animals in vivo. Unlike most other treatments for osteoporosis, the resulting bone accretion resulted from enhanced bone formation rather than suppressed bone resorption. It is possible that Abatacept could also be used to amplify the activity of Forteo, thus reducing the frequency of daily doses of Forteo administration and/or reducing the total dose of Forteo needed.
- Twice weekly treatment of Abatacept for 24 weeks in vivo in a mouse model (equivalent to monthly administration in humans) significantly increased bone mineral density.
- Increased bone mass in these mice resulted from enhanced bone formation rather than suppressed bone resorption.