Professor Wischik and his team have been conducting extensive preclinical and early clinical studies into Tau Aggregation Inhibition for the past 25 years. To support their research, they have developed and patented several proprietary tools, including cell-based assays, in vitro assays, screening platform, and transgenic animal models.
Methylthioninium chloride (MTC) was the first TAI studied by Professor Wischik and colleagues. MTC had a previous long history of use in the treatment of malaria and other infections prior to Professor Wischik’s discovery in the mid-1980s that it could dissolve Tau tangles. The drug was tested in vivo in two transgenic mouse models. In both studies, MTC was able to reverse the behavioural and pathological effects arising from tau pathology. The team concluded that MTC had the potential not only to slow the rate of Alzheimer’s progression, but may even halt it and restore neuronal function, particularly at early stages of the disease. This formed the basis for further development of TauRx’s first generation TAI, rember®, and subsequent follow-on molecules.
TauRx’s first-generation TAI, rember®, was a proprietary form of MTC and the first TAI to be tested in clinical trials for Alzheimer’s. Following the encouraging results from their Phase 2 study of rember® in mild and moderate Alzheimer’s, the team set out to improve the molecule for enhanced bioavailability and tolerability. The result was LMTX™ (leuco-methylthioninium), a completely new chemical entity that delivers the same active moiety into the bloodstream as its predecessor, rember® but in a more efficient manner.
The TauRx team has conducted several animal studies evaluating the pharmacokinetic properties and bioavailability of LMTX™. Additionally, they have determined the compound’s efficacy on tau pathology in two tau-transgenic mouse models which produce tau pathology. In these studies, they also measured the brain concentration at which effect on tau pathology is observed, and related this back to plasma levels in humans and plasma and brain levels in pigs. The FDA granted TauRx permission to proceed to Phase 3 studies of LMTX™ based on the data presented.