I035 Preclinical studies to enable phase 1b/2a safety and tolerability of human neural stem cells for HD (REGEN4HD)

<h3>Background</h3> Huntington’s disease (HD) is a potential indication for regenerative medicine given it is an inherited disorder caused by a single known mutation that has no currently available disease modifying treatment. Effective neurorestorative or neurodegenerative strategies based on human stem cell products offers a potential treatment option that could modulate disease pathology in a complex tissue such as the brain. <h3>Aims</h3> We propose to evaluate a human neural cell product, hNSC-01, as a potential cell- based therapy for HD. The proposed clinical trial is aimed at evaluating safety and tolerability of the cell-based therapy. <h3>Methods, Results and Outcomes</h3> We have carried out extensive preclinical testing of hNSC-01 and find that cells transplanted following intrastriatal injections have pleiotropic effects in multiple HD mouse models including they: 1) provide trophic support, 2) undergo differentiation in vivo and potentially form synaptic connections with the host tissue, 3) reduce aberrant huntingtin accumulation, 4) are electrophysiologically active and provide electrophysiological rescue and 5) provide molecular benefit to host tissue. Cells survive in genetic mouse models of HD for the duration of the preclinical studies without acquisition of mutant Huntingtin (mHTT) phenotypes. A short-term safety and targeting study was carried out in non-human primates. <h3>Conclusions</h3> Pivotal preclinical safety tumorigenicity and toxicology studies have been carried out in HD mice with no negative outcomes, supporting safety of the clinical product and approach. An IND was granted by the FDA for an upcoming Phase 1B/2A clinical trial.