The Problem
After a traumatic injury, fractured bones have the remarkable ability to heal themselves, often restoring the affected area either partially or fully. However, of the estimated 6.8 million fractures that occur annually in the United States, between five and ten percent (up to 680,000 cases) experience delayed or incomplete healing, leading to impaired mobility and prolonged recovery.
Currently, no federally approved medical therapies are available to stimulate fracture healing. As a result, patients with poor fracture healing may endure persistent pain, disability, and a compromised quality of life. To address these challenges, innovative treatments are urgently needed to accelerate bone regeneration and improve outcomes.
The Approach
Marc Wein, MD, PhD, an endocrinologist at Massachusetts General Hospital, received the 2021 Stepping Strong Breakthrough Award for discovering a therapy pathway that stimulates bone regeneration and enhances fracture healing.
Dr. Wein and his team found that inhibiting two specific enzymes—salt inducible kinases 2 and 3 (SIK2 and SIK3)—can trigger a powerful anabolic response in bone tissue. These kinases are crucial for regulating cellular processes in response to stress, such as fractures. By inhibiting SIK2 and SIK3, the body can build complex molecules from simpler ones, promoting bone growth, repair, and regeneration. With this knowledge, Dr. Wein is investigating various strategies to deliver gene therapies that specifically target SIK2 and SIK3 in traumatic fractures. This research has the potential to lay the groundwork for new treatments that could significantly improve care and accelerate the recovery of individuals with poor fracture healing.
What’s Next?
With support from the Stepping Strong Innovator Award and Stepping Strong Breakthrough Award, Dr. Wein’s discovery offers a solution beyond traumatic injury for treating bone damage caused by aging, repetitive motion, and bone-weakening conditions such as osteoporosis and cancer. Tara Ciongoli, a member of the Stepping Strong Advisory Board, was born with a brittle bone disease that causes her bones to be rigid, calcified, and prone to fractures. With her personal connection to bone health, Tara understands the transformative potential of this research, not only for people like herself but fracture patients everywhere. As she described in an interview with WCVB, “There were doctors doing this incredible work that wouldn’t only benefit me and my particular bone disease, but would benefit people undergoing trauma with bones down the road and anywhere in the world.”
In the lab, Dr. Wein’s team has observed robust gene silencing effects and is actively exploring different formulations to translate this approach to living organisms. Meanwhile, Dr. Wein has found that embedding parathyroid hormone into orally delivered hydrogels can effectively promote fracture healing in animal models. This development opens a new research direction, made possible through the support of The Gillian Reny Stepping Strong Center for Trauma Innovation, and is offering new avenues for advancing bone healing therapies.
