Cell-Penetrating SIL1 Protein Replacement Therapy for Marinesco-Sjogren Syndrome

Marinesco-Sjögren syndrome (MSS) is a rare genetic disease of infancy linked to mutations in the SIL1 gene. Individuals with MSS suffer various disabilities, including loss of motor coordination due to cerebellar degeneration, and skeletal muscle weakness. After a progressive phase, symptoms stabilize and patients live to old age. Therefore, any treatment that prevents, delays or attenuates cerebellar degeneration and/or muscle pathology may significantly improve the patients’ quality of life.

Previous studies reported that reintroduction of the SIL1 gene prevents cerebellar degeneration, and preserve motor function in mice carrying the same genetic defect as in human patients. Our laboratory generated preliminary evidences that a modified form of the protein SIL1 capable of entering the cells can repair malfunctioning cells obtained from a patient affected by MSS.

Therefore in the present project, we propose to test a protein replacement therapy aimed at restoring the function of SIL1. The effect of this novel potential treatment will be studied both in cells obtained from a MSS patient and in muscle cells artificially deprived of SIL1. Finally, the modified SIL1 protein will be administered to the mouse that carries the same genetic defect as human patients to see if the treatment improves motor performance. We hope this innovative strategy will help develop an effective therapy for MSS.