The preprint manuscript Assessment of levamisole HCl and thymosin α1 in two mouse models of amyotrophic lateral sclerosis by David R Borchelt (Department of Neuroscience, University of Florida, College of Medicine, Gainesville, FL) and Siobhan Ellison (Neurodegenerative Disease Research Inc., Fairfield, FL) has posted on bioRxiv. The study, conducted at The Jackson Laboratories (Bar Harbor, ME) examined the potential utility of two drugs that have indications as immune modulators, levamisole HCl and thymosin α1 (Zadaxin) in the SOD1G93A and Prp-TDP43A315T mouse models of ALS. Outcome measurements included efficacy assessment on the neuromuscular phenotypes, and pathological analyses of ubiquitin load and neuro-inflammatory markers in spinal motor neurons. Neither of these drug treatments produced significant extensions in survival; however, there were changes in ubiquitin load that suggest the drugs could be beneficial as additions to other therapies.
NDR continues to conduct studies to modify levamisole and drugs that bind thymopentin receptors increasing the immune modulation that would benefit ALS patients. If levamisole were to be developed for treatment of neurological diseases a significant consideration would be preventing the reversible side effects through drug design. The modifications to thymopentin-mimics that are most promising are molecules that increase stability and maintain safety. Currently NDR is pursuing an IND for a retro-enantiomer of thymopentin. Our goal is a Phase I open label study starting in the second quarter of 2023.