Therapeutics: Brain-derived neurotrophic factor (BDNF); neurotrophic tyrosine kinase receptor 2 (TrkB; NTRK2); excision repair cross-complementation group 6 (ER
Patient sample and cell studies suggest BDNF, BDNF mimetics or other agonists of its receptor, TrkB, could help treat Cockayne syndrome, a leukodystrophy caused by ERCC6 mutations that is associated with defects in neurogenesis and neuron differentiation. In postmortem brain tissue samples from Cockayne patients, BDNF and TrkB levels were lower than in samples from control donors. In an ERCC6-knockdown human neuronal progenitor cell-based model of the disease, the BDNF mimetic amitriptyline increased levels of a marker of neuronal differentiation compared with vehicle. In neurons generated from Cockayne syndrome patient-derived induced pluripotent stem (iPS) cells, amitriptyline or a TrkB agonist tool compound increased neurite outgrowth and expression of a marker of neuronal differentiation compared with vehicle. Next steps could include a clinical trial of amitriptyline to treat Cockayne syndrome...