Data from both human studies and preclinical models points to an increase in neuronal firing, or hyperexcitability, in ALS neurons (see Jan 2015 news story; Bae et. al., 2014). Last year, work from the groups of Kevin Eggan at the Harvard Stem Cell Institute (HSCI) in Cambridge, MA and Clifford Woolf at the Boston Children’s Hospital demonstrated that the anti-epileptic drug retigabine is effective in reducing hyperexcitability in stem cells derived from ALS patients (Wainger et. al., 2014; April 2014 news story). The first author on that study, Brian Wainger, is now the principal investigator of a clinical trial testing the ability of retigabine to reduce neuronal hyperexcitability in ALS patients. In parallel, samples will be collected to derive stem cells from participating patients to examine whether predictive measures of drug efficacy can be identified. The study will be conducted at 12 sites in the Northeast ALS Consortium (NEALS), with drug provided by GlaxoSmithKline (GSK) and funding from the HSCI, the ALS Association, GSK and the MGH Neurological Clinical Research Institute (MGH NCRI). This trial is remarkable as it is the first to be initiated based solely on preclinical evidence from patient-derived stem cells without companion mouse studies. As Lucie Bruijn, Chief Scientist for the ALS Association, said: “It is our hope that this novel approach demonstrates promising results and leads to better clinical trials for ALS patients in the future”.
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