Gene Therapy Offers Hope for Lifelong Treatment of Rare Bone Disorder

Hypophosphatasia (HPP), a rare genetic disorder characterized by abnormal bone development and premature tooth loss, has been typically treated with frequent injections of enzyme replacement therapy. Despite its life-saving potential, this treatment remains invasive and often leads to adverse reactions among patients. **In a groundbreaking study**, researchers led by Dr. José Luis Millán at Sanford Burnham Prebys have taken crucial steps toward a revolutionary treatment for HPP using gene therapy. The study, published in the Journal of Bone and Mineral Research, highlights the potential of AAV8-TNAP-D10, a virus engineered to carry the gene for the missing enzyme, TNAP, needed to correct bone and tooth malformations. The research team focused on determining the optimal dosage that balances efficacy with the minimization of side effects. Unexpectedly, they discovered that the therapy was more effective in female mice with late-onset HPP, achieving results with lower doses. **This sexual dimorphism was noted**, although it's unlikely to appear in humans based on current knowledge. The study sets the stage for clinical trials, moving closer to a future where a single injection could offer a lifelong solution to HPP patients. Looking ahead, Dr. Millán emphasizes the importance of understanding long-term implications and the broader physiological role of TNAP, as the enzyme is expressed in various other organs. This research received funding support from NIH and other entities, paving the way for future advancements.