Fragile X Syndrome (FXS)
FXS is the most common inherited cause of intellectual disability and the most common cause of autism spectrum disorder. The condition is caused by a faulty FMR1 gene, which in turn disrupts production of a protein called Fragile X Mental Retardation Protein or FMRP. This protein plays a key role in developing synapses, the connections between nerve cells that relay nerve signals. The resulting damage to nervous system function causes a range of serious cognitive and behavioral disabilities.
Lysogene entered into a research partnership agreement with French technology transfer organization SATT Conectus, and the laboratory of Dr. Hervé Moine, a researcher within Prof. Jamel Chelly’s team at the Institute of Genetics and Molecular and Cellular Biology IGBMC in Illkirch, Strasbourg (CNRS, Inserm and Strasbourg University).
Dr Moine’s team discovered an enzyme regulated by FMRP, called diacylglycerol kinase K (DgkK), which constitutes a promising new therapeutic target for treating FXS. Lysogene, together with its academic partners, aims to develop an innovative AAV-based gene therapy based on Dr Moine’s discovery.
The partnership was facilitated by the Fondation Maladies Rares, through its POC Club promoting research and knowledge management with academic and industrial actors in the field.
Upon completion of the research collaboration, Lysogene has an option to obtain an exclusive commercial license to the technology.
Neuronopathic Gaucher and Parkinson’s disease
Neuronopathic Gaucher disease is a rare lysosomal storage disease caused by mutations in the GBA1 gene. The GBA1 gene encodes β-glucocerebrosidase, the enzyme responsible for the breakdown of the glycosphingolipid glucocerebroside. In neuronopathic Gaucher disease, GBA1 gene mutations strongly lower enzyme activity, causing a toxic buildup of glucocerebroside in the central nervous system that leads to neurological pathology.
Mutations in the GBA1 gene have recently emerged as the most common genetic abnormality associated with Parkinson’s disease. Parkinson’s disease is the second most common neurodegenerative disorder, affecting 2–3% of the world population over the age of 65. Nearly 10% of Parkinson patients have mutations in the GBA1 gene.
Currently, there is no effective treatment for the severe neurological symptoms associated with neuronopathic Gaucher disease, and no disease-modifying treatment for Parkinson’s disease.
Lysogene has entered into a collaborative research agreement with Yeda Research and Development Co Ltd, the commercial arm of the Weizmann Institute of Science.
Lysogene will be collaborating with the lab of Prof. Anthony Futerman at the Weizmann Institute of Science to develop a novel AAV gene therapy approach for neuronopathic Gaucher disease, Parkinson’s disease, and other diseases associated with GBA1 gene mutations.
Lysogene will provide expertise in AAV vector design and production, and Prof. Futerman’s lab will provide glucocerebrosidase variants with enhanced biological properties and conduct biological proof and concept studies.
Upon completion of the research collaboration, Lysogene has an exclusive option to license the program.