A preclinical study to treat neuromuscular disease caused by mutations in the small heat check protein HSPB8.

Patients with autosomal dominant distal hereditary motor neuropathy (dHMN) develop progressive motor impairments, weakness and wasting of lower limb muscles. We identified mutations in the small heat shock protein HSPB8 as one of the underlying genetic causes for this disease. More recently, distal myopathy was also found to be associated with mutations in HSPB8. So far, no treatment is available to delay or cure patients with mutations in HSPB8. Our research group generated a mouse model mimicking the symptoms observed in affected individuals by introducing a known disease-causing mutation (knock-in: KI). Additionally, we also generated a mouse model in which HSPB8 was deleted (knock-out: KO). Strikingly, the latter does not show any sign of neuronal damage or severe myopathy. We therefore hypothesise that reducing the levels of HSPB8 might help to alleviate the symptoms associated with dHMN. This project aims to identify therapeutic compounds that by reducing HSPB8 levels, can rescue or delay the neurodegeneration observed in the KI model. It could therefore deliver the first small molecule treatment for neuropathies and myopathies caused by mutations in HSPB8. Furthermore, this strategy will also open therapeutic possibilities for other neuromuscular and neurodegenerative diseases where HSPB8 plays a role in the pathology.

Keywords:MOUSE MODELS

Disciplines:Biological system engineering, Biomaterials engineering, Biomechanical engineering, Medical biotechnology, Other (bio)medical engineering