L-Serine Study Results

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DELAYED-START TRIAL TO EVALUATE THE SAFETY AND EFFICACY OF L-SERINE IN SUBJECTS WITH HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY TYPE 1 (HSAN1)

Vera Fridman1, Peter Novak2, William David3, Anne Louise Oaklander3, Eric Macklin3, Diane McKenna-Yasek2, Kailey Walsh3, Robert Brown2, Thorsten Hornemann4, Florian Eichler3  1University of Colorado Medical Center, Denver, US., 2University of Massachusetts Medical School, Worcester, US.,3 Massachusetts General Hospital (MGH), Boston, US., 4University Hospital Zurich, Clinical Chemistry, Zurich, Switzerland.

Introduction: Hereditary Sensory Autonomic Neuropathy Type 1 (HSAN1) is a severe, autosomal dominant, axonal neuropathy that manifests with marked, small fiber predominant sensory loss, variable degrees of limb weakness, and skin ulceration. HSAN1 is caused by mutations in the SPTLC1 and SPTLC2 genes, which encode two of the three subunits of the enzyme serine palmitoyltransferase (SPT). Mutations in SPT induce a permanent shift in the substrate preference from serine to alanine thereby forming a class of neurotoxic deoxysphingolipids (dSL). Supplementation with L-serine reduces dSL levels in transgenic HSAN1 mice and results in clinical improvement of neuropathy. We report a two-year, delayed-start, placebo-controlled clinical trial evaluating the safety and efficacy of oral L-serine (400 mg/kg/d) in human subjects with HSAN1.

Results: All but 2 subjects (both of whom

Continue Reading →

HSAN1 Conference April 18-21, 2017

An international cadre of experts gathered in April in Boston to discuss the chemistry, biology, genetics, neuropathy, treatment, and potential for cure for HSAN1.They were joined by post-doctoral fellows, doctors, researchers, and 5 members of the Deater family. The welcome dinner provided time to fellowship and talk about funding issues and possibilities, as well as to remember Larry Deater and his dedication to this ongoing research.

Dominic Campopiano- Edenborough Scotland- discussed the basic chemistry of the biosynthesis of the enzyme serine palmitoyltransferase (SPT). The SPTLC1 gene provides instructions for making one part (subunit) of the SPT enzyme. The mutation of the gene interferes with the mechanism of the enzyme SPT. A question that remains is, “how is SPT regulated by the cell?”

Tere sa Dunn-Giroux- Bethesda Maryland- is focused on identifying and characterizing the enzymes responsible for sphingolipid synthesis, on determining how sphingolipid synthesis is regulated, and on clarifying the functions of these important lipids through a genetic and biochemical approach. The enzyme is more complex than previously thought.

 

 

Thorsten Hornemann- Zurich Switzerland- discussed the role of sphingolipids in the body. They play a major role in the neurological system- brain and nerves. We know that the blood

Continue Reading →