Today, more than 73 chromosomal regions are known to carry mutations responsible for spastic paraplegia, but it is estimated that almost 50% of families do not have a known genetic mutation, which justifies active genetic research into these diseases.
But it is also essential to understand the biological effects of known mutations in order to open up new therapeutic avenues.
At the Paris Brain Institute
Researchers in the “Fundamental and Translational Neurogenetics” team, co-directed by Alexandra DURR and Giovanni Stévanin, aim to identify new genes or molecular dysfunctions that cause or influence spastic paraplegia through genomic analysis of familial forms.
The study Identifying a key mechanism in type 11 hereditary spastic paraplegia, led by Frédéric Darios and Giovanni Stevanin, highlighted the role of the accumulation of certain lipids in type 11 hereditary spastic paraplegia. These results suggest that targeting this mechanism could be an interesting therapeutic avenue in this disease.
The collaborative study Hereditary spastic paraplegia type 58, a demyelinating disease, led by Khalid Hamid El Hachimi of the Institut du Cerveau and Amandine Duchesne of INRA, reports that mutations in the KIF1C gene, responsible for hereditary spastic paraplegia type 58 (SPG58/SPAX2), lead to a loss of myelin. This discovery could lead to progress in understanding the mechanisms of hereditary spastic paraplegia type 58.
The study Hereditary spastic paraplegia: identifying the impact of each mutation, by the research team led by Giovanni Stevanin (INSERM/EPHE), highlights the effect of certain mutations in hereditary spastic paraplegia. It highlights the need to develop tools for interpreting the biological effects of mutations in human genetics.
The studyWhen spatacsine stops working, motor neurons degenerate, links neuronal degeneration, lysosome dysfunction and lipid metabolism. Numerous proteins encoded by genes affected in hereditary spastic paraplegia are also recurrently involved in these mechanisms, and understanding them could open up new therapeutic avenues.