Preventing Arthritis After Injury—and Before Symptoms Arise
Arthritis affects millions of people and animals worldwide, resulting in not only pain and morbidity but also in significant economic burden to society due to loss of work and associated medication. Current treatments are aimed at alleviating pain, but none address the actual disease process. To affect the pathogenesis of arthritis, intervention must happen early, before irreversible joint damage occurs.
Lisa A. Fortier, Clinical Sciences, and her team are working to understand the acute (within minutes to hours to days) events that happen after joint injury so that arthritis can be prevented, not just symptomatically treated.
Mitochondria are commonly known as the power house of cells, but they are also intimately involved in other cellular processes such as generation of reactive oxygen species and cell death. Mitochondrial dysfunction has been identified in end-stage arthritis, at the point of joint replacement surgery; but the role of mitochondria in the initiating events of arthritis have been previously unexplored. Data from Fortier’s laboratory, resulting from PhD student Michelle Delco’s work, indicate that mitochondrial dysfunction is an acute event in cartilage after joint injury, resulting in cartilage destruction and arthritis.
Fortier’s lab has successfully reversed this mitochondrial dysfunction and prevented cartilage matrix degradation with a drug called SS-31, discovered by retired professor Hazel H. Szeto, Pharmacology at Weill Cornell Medicine. SS-31 is specifically targeted to the inner mitochondrial membrane where it binds to and stabilizes cardiolipen, restoring normal mitochondrial function and therefore cell health. Present studies aim to determine if SS-31 can prevent the development of arthritis after joint trauma in vivo and to further understand the molecular mechanism by which SS-31 protects articular cartilage. NIH Award Number: 1K08AR068470-01A1