Patient-derived stem cells to characterize rare genetic disease

Jonas van lent, MSc, PhD student/ Supervisor Prof. Dr. Vincent Timmerman, PhD 
Peripheral Neuropathy Research Group, University of Antwerp, Belgium

Our lab at the University of Antwerp, Belgium, has a longstanding research interest in the molecular genetics of inherited peripheral neuropathies. Specifically, we aim to gain molecular insights in underlying disease mechanisms of the peripheral nerve. One of our focus is the study of rare genetic mutations causing hereditary sensory and autonomic neuropathy type 1 (HSAN-I). 

Ten years ago we discovered HSAN-I associated mutations in the SPTLC2 gene coding for one of the different subunits of the serine palmitoyltransferase (SPT). Note that HSAN-I disease causing mutations were found before in the SPTLC1 gene. From then on, we gained an increasing knowledge in the disease mechanisms of SPTLC1 and SPTLC2 mutations. In HSAN-I, the substrate specificity of the SPT enzyme is altered by mutations in one of both genes. Instead of using the amino acid L-serine, the mutant SPT enzyme now metabolizes L-alanine or L-glycine, causing the formation of neurotoxic products (known as deoxysphingolipids). 

Recent clinical studies revealed that L-serine supplementation (providing an excess of L-serine will thereby decrease the relative abundance of L-alanine/L-glycine) improved the neuropathy symptoms of patients due to a reduction of the neurotoxic products.

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