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07 Jun 2016

Innovative biotherapies: towards high-precision medicine

Illustration for article: Innovative biotherapies: towards high-precision medicine
A team of researchers from the I-Stem laboratory has identified, thanks to the screening of a cellular neuronal model derived from stem cells, therapeutic compounds for an autistic disorder of genetic origins, opening the way towards high-precision medicine.
As part of a study on Phelan-McDernid syndrome, a rare autistic disorder of genetic origins, a team of researchers from I-Stem (CECS/AFM-Téléthon/Inserm), led by Alexandra Benchoua and Marc Pechanski, in collaboration with Pr. Thomas Bourgeron (Institut Pasteur/Paris Diderot University/CNRS) and Richard Delorme (Robert Debré hospital, AP-HP), has managed to highlight the therapeutic potential of lithium on a patient affected with this disease.
 
A large part of the persons affected by this condition lose a fragment of chromosome 22, which carries one of the two copies of the SHANK3 gene. This loss results in a significant decrease of the amount of SHANK3 protein and leads to damages in the synapses.
 
To limit these damages, scientists aimed at increasing the expression of the remaining copy of SHANK3 in order to rebalance the amount of the protein. To do so, they developed a model allowing the production in vitro of human neurons from pluripotent stem cells.
 
A high-throughput screening of 202 pharmacological compounds followed to determine those that are more likely to increase the expression of the SHANK3 gene in neurons. Lithium and valproic acid turned to be the most compelling compounds among those tested. A lithium pharmacotherapy was then practised for a year on the patient for whom lithium had proved its efficiency.
 
This treatment’s results are very encouraging because the degree of severity of the patient’s autism has decreased. A randomised, doubleblind trial is now being prepared by researchers to confirm those results.
 
This work has proven the benefit of cell models derived from pluripotent stem cells in the research of treatments for autistic disorders linked to genetic disorders. This methodology could be used for other neurological or psychiatric diseases, opening the way to high-precision medicine.