Tushar Tangsali, father to two sons with Duchenne muscular dystrophy (DMD), discusses how he’s working to develop a gene therapy for a unique genetic variation of DMD for his sons.
DMD is a rare genetic, neuromuscular condition characterized by progressive muscle wasting. Symptoms of DMD include progressive weakness and atrophy of both skeletal and heart muscle. Early signs may include delayed ability to sit, stand, or walk and difficulties learning to speak. DMD is caused by genetic changes in the DMD gene.
Mr. Tangsali’s sons are not currently eligible for any of the current therapies, approved or in development, for DMD, due to their unique genetic mutations (8-25delhmdx) of which they are the only two patients in the world. Gene therapies are developed for mutations in a specific region in the dystrophin gene, which accounts for 70% of patients with DMD. Additionally, exon skipping therapies are focused on skipping one exon in that specific region, excluding them from both possibilities.
In 2021-2022, a new gene therapy was developed with sRNA-based skipping that shows promise for patients who need more than one exon skip and different targeting. It was then that Mr.Tangsali reached out to the physicians and researchers working on this and got started testing the technology for his sons’ mutations with the help of CureDuchenne.
Mr. Tangsali has now developed mouse models, working to see if skipping exons 6, 7, and 8 will result in a functional and stable protein and colony phenotyping. The first set of data is expected in early 2027, and if positive will lead to further testing on safety, efficacy, and use in his sons.
Currently, all of the work done has been self-funded by the Tangsali family. However, going forward will require additional funding.
To learn more about DMD and other rare musculoskeletal diseases, visit https://checkrare.com/diseases/musculoskeletal-diseases/
Links to labs:
JAX is building two mouse models- 8-25delhmdx is the disease model of my boys’ mutations, and 6-25del is the easiest fix by skipping exons 6 and 7.
The Rare Disease Translational Center
Base used for creating the models: C57BL/6J (Jax stock #664) genetic background