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Research on rare genetic diseases impacting brain development with Prof Olivier Braissant

Professor Olivier Braissant is the head of the Metabolic Unit at the Service of Clinical Chemistry of the University Hospital of Lausanne (CHUV). Within the Service, the Clinical Chemistry Laboratory performs clinical chemistry analyses for the patients of the hospital, including for the diagnosis and follow-up of patients presenting inborn errors of metabolism (IEM). Within the Metabolic Unit of the Service of Clinical Chemistry, Olivier Braissant developed, since more than 20 years, his own research line on IEM affecting the brain development. In particular, he became one of the World’s leaders on two categories of these rare genetic diseases affecting brain development : 1) Cerebral Creatine Deficiency Syndromes (CCDS), comprising AGAT and GAMT deficiencies (affecting the two enzymes of the creatine synthetic pathway) as well as the Creatine Transporter Deficiency (CTD); and 2) Urea Cycle Diseases, and in particular how these genetic diseases can intoxicate the brain through ammonium accumulation.

For CCDS, Olivier Braissant, through the use of various in vitro and in vivo experimental models, has contributed to the understanding on how the blood-brain barrier is poorly permeable for creatine, leading the central nervous system to express the creatine synthetic pathway (with AGAT and GAMT enzymes), and how this synthetic pathway, which includes the creatine transporter SLC6A8, contributes to maintain sufficient amounts of creatine for the brain.

Olivier Braissant also develops different experimental models of CCDS, both in vitro and in vivo, to better understand these three genetic diseases, and to contribute to the development of new treatment strategies, in particular for CTD which is not treatable so far despite more than 20 years of research worldwide. Through the use of a new in vivo knock-in rat model mimicking CTD, Olivier Braissant hopes to bring, within the next months, the successful proof of concept of a new strategy making use of gene therapy through AAV vectors transduction of the CTD brain, therefore correcting the disease.