Professor Wischik and his team have been conducting extensive research into tau aggregation inhibition for the past 25 years. To support their research, they have developed and patented several proprietary screening tools, including cell-based assays, in vitro assays and transgenic animal models.
Methylthioninium chloride (MTC) was the first tau aggregation inhibitor (TAI) studied by Professor Wischik and colleagues. MTC, also known as “methylene blue”, 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. MTC was able to reverse the behavioural and pathological effects arising from tau pathology in animal models, and the team concluded that MTC had the potential to slow the rate of Alzheimer’s progression, and potentially restore neuronal function, particularly at early stages of the disease.
TauRx’s first-generation TAI, rember®, was a proprietary, highly-purified 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 new chemical entity that delivers the same active moiety into the bloodstream as rember®, but in a more efficient manner.
The TauRx team has conducted several studies to evaluate the pharmacokinetics and bioavailability of LMTX®. Additionally, they have determined the compound’s efficacy on tau pathology in two transgenic mouse models which produce tau pathology. In these studies, they also measured the brain concentration at which an 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.