With regard to the causes of spastic paraplegia, in 70% of cases the mode of transmission of the disease is autosomal dominant. 20% of the families have autosomal recessive transmission and transmissions of spastic paraplegia linked to the X chromosome are estimated at 2%.
Causes of Spastic Paraplegia
Today, more than 73 chromosomal regions are known to carry mutations responsible for spastic paraplegia, however, it is estimated that nearly 50% of the families in which the genetic mutation is not known, which justifies active genetic research on these pathologies.
But it is also essential to understand the biological effects of known mutations in order to open new therapeutic avenues.
At Paris Brain Institute
The researchers of the team “Fundamental and Translational Neurogenetics” co-led by Alexandra DURR and Giovanni Stevanin have the objective of identifying new genes or molecular dysfunctions that cause or influence spastic paraplegia through the genomic analysis of family forms.
The study, Identification of a key mechanism in hereditary spastic paraplegia type 11, led by Frédéric Darios and Giovanni Stevanin, demonstrated the role of lipid accumulation in hereditary spastic paraplegia type 11. These results suggest that targeting this mechanism may provide an interesting therapeutic pathway in this pathology.
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), cause a loss of myelin. This finding could lead to advances 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. She stressed the need to develop tools to interpret the biological effects of mutations in human genetics.
The study, When the spatacina no longer functions, motoneurons degenerate, links neuronal degeneration, lysosome dysfunction and lipid metabolism. Numerous proteins, encoded by genes affected in hereditary spastic paraplegia, are also repeatedly involved in these mechanisms, the understanding of which opens the way to new therapeutic avenues.
