Lowering ApoE to improve age-related bone fracture healing
Bone fractures occur in 50% of the population, causing significant morbidity and mortality and costing the US health care system over $20 billion annually. Complications, such as nonunion or delayed union, occur in 5%–10% of fracture cases, and this rate is increased in the elderly population. One of the most common health issues in the elderly is bone degradation that can lead to bone fractures. This condition can be detrimental for the elderly due to slow bone healing, and statistics show that every 3 seconds there is a bone fracture occurring. While there are preventative medications to decrease bone fractures, currently, there are no reliable therapeutics to help bones heal after a fracture occurs in the elderly. Because of this unmet need, there is an interest in identifying new therapies to help bone fracture healing.
In previous studies, Dr. Baht discovered that there are multiple proteins that change as an individual ages. One protein of interest is a lipoprotein that has been shown to be correlated to decreased bone healing and through Dr. Baht studies, increases as people age. Furthermore, in osteoblast, adding lipoprotein decreased bone healing markers in vitro. In a more clinically relevant scenario, using a viral vector to decreased lipoprotein in aged mice with bone fractures showed that decreasing circulating levels of the lipoprotein lead to increased bone healing. This finding suggests that, by reducing or inhibiting this lipoprotein can be used as a therapeutic to increase age-related bone fractures.
Lipoproteins have also been associated to promote pathogenesis of Alzheimer’s disease and atherosclerosis. Reducing lipoprotein levels in these patients could have a positive therapeutic effect.
Current intervention therapeutics includes preventative measure therapies (Prolia® and Fosamax) that only benefit certain elderly population, while removal of circulating lipoprotein through a gene therapy approach would benefit all individuals at risk or with bone fractures.
Second intervention for standard of care can include bone grafts, but these are only applicable to easy to access bone fractures. Lipoprotein knockdown will not pose this issue.