Gene Therapy Shows Promise in Treating Rare Genetic Disorder HSP

There is no cure for the rare disease Hereditary Spastic Paraplegia (HSP), but researchers from Drexel University's College of Medicine and the UMass Chan Medical School have achieved proof-of-principle success with "silence and replace" gene therapy—an approach that uses a viral vector to silence genes with disease-causing mutations and replace them with healthy genes—to prevent and even reverse disease progression. In this case, the team, led by Drexel College of Medicine Professor Peter Baas, Ph.D. and Research Instructor Emanuela Piermarini, Ph.D., who was chief scientist on the project, were able to prevent nerve breakdown and symptoms of HSP in a mouse model of the disease. Their findings arepublishedin the journalMolecular Therapy. HSP can be caused by mutations in any of more than 90 different genes, each with a numbered name, such as SPG1, SPG2 and so on. The team studied SPG4, the most common form of HSP, making up about 40% of cases and caused by mutations in the SPAST gene. Patients are generally categorized as having uncomplicated HSP––the majority of cases––categorized by gait defects, such as muscle stiffness and weakness in leg muscles or complicated HSP, which, in addition to muscle weakness and stiffness, may also include symptoms impacting upper limb mobility, speech or intellectual abilities and/or bladder control, among other symptoms.