An Herbal Derivative as the Basis for a New Approach to Treating Post-Traumatic Osteoarthritis
Abstract
Osteoarthritis (OA) is the most common cause of disability in adults, and the most common cause of disability among military Service members who are removed from active duty for medical reasons. Post-traumatic osteoarthritis (PTOA) is a cause of disability in young adults who are exposed to traumatic joint damage and is therefore a major concern for military personnel. OA is a painful disease that involves the progressive deterioration of joint structures such as cartilage that coats the end of bones. As cartilage is destroyed over time, bones begin to rub together, further damaging the joint and making it difficult to perform daily activities or to even move with ease. Progressive joint deterioration in OA is accompanied by cellular and biochemical changes that drive and mediate the tissue destruction. We believe that this "progressive phase" of the disease provides a good target for therapeutic intervention that ultimately will prevent joint damage. In PTOA, this progressive disease phase is shortened, leading to rapid onset disability in young otherwise healthy individuals. Treatment of PTOA currently involves symptom management and likely culminates with surgical joint replacement. There are no good treatment options to arrest OA disease development. New approaches to the treatment of PTOA therefore represent a major unmet medical need for active military personnel, as well as for military Veterans. The goal of this study is to develop and validate in an animal model of PTOA a practical new class of therapeutics that targets the progressive phase of PTOA. Unlike existing treatments, these drugs are meant to arrest disease progression and prevent the onset of PTOA-related disability. This drug class is based on halofuginone (HF), a compound that is derived from the active ingredient in an herbal remedy originally used in traditional Chinese medicine. Our lab recently solved HF s therapeutic mechanism of action. Preliminary data from a mouse model of PTOA show that HF potently suppresses disease development. Data from cartilage cells and cells that make up the synovial joint lining show that HF and related compounds suppress the tissue destructive program that is activated during the progressive phase of PTOA. Our work in this grant will expand these studies and provide the basis for developing this drug class for treatment of human PTOA in the near term.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510397
Entities
People
- Yefu Li
Organizations
- Harvard University
- United States Army