Machado–Joseph disease treatment using self-assembled siRNA

Machado-Joseph disease  is a fatal autosomal dominant hereditary ataxia characterized by cerebellar ataxia and caused by CAG expansion in ATXN3. There is no effective treatment currently for the disease.

The researchers created self-assembling vesicles to deliver siRNAs targeting mutant ATXN3 to the cerebellar cortex and spinal cerebellar tract, reducing pathology in MJD mice.

The authors show that the number of Purkinje cells in the cerebellar cortex was significantly increased, and the loss of myelin basic protein was reduced. Moreover, the quantity of neurotoxic nuclear inclusion bodies and the expression of glial fibrillary acidic protein, which promotes neuroinflammation in activated astrocytes, were decreased significantly. They also found significant improvements in motor balance ability and reduction of cerebellar atrophy.

https://academic.oup.com/brain/article/148/3/817/7771322

https://sciencemission.com/Machado%E2%80%93Joseph-disease-SiRNA