Preclinical results from TauRx Therapeutics Ltd (Aberdeen, Scotland) have indicated that LMTM, the active agent in its LMTX® drug originally developed for Alzheimer’s disease (AD) treatment, may also be beneficial as a Parkinson’s disease (PD) medication.
LMTX is a reduced form of methylthioninium, which has previously shown promising results in trials in mild to moderate AD. The most recent study utilized two transgenic mouse models with induced synucleinopathies, termed L58 and L62, which had been characterized in previous studies.
Both groups developed mobility and behavioural abnormalities classically observed in PD, and interestingly, the L62 model, which exhibited higher levels of alpha-synuclein (a-syn) aggregation, progressed in an age-dependent manner, whilst age-related accumulation was less pronounced in L58 mice.
The two groups of mice were treated with LMTX via oral administration for 6 weeks, with both cohorts demonstrating significant reductions in levels of a-syn pathology in various brain regions by the end of the study. Normal mobility and behaviors were also restored in the animals.
Synucleinopathies are common to multiple neurodegenerative disorders; hence the findings may herald further research into novel treatments, as summarized by Franz Theuring (University of Berlin, Germany), a collaborator on the project: “The results seen in these animal models open up the possibility of near-term testing of LMTM in patients with PD or dementia with Lewy bodies resources permitting. The results also suggest the exciting possibility that a single drug could be used at different doses to treat a range of severely debilitating neurodegenerative disorders, even though they have different underlying pathology at the molecular level.”
Sources: Schwab K, Frahm S, Horsley D et al. A protein aggregation inhibitor, leuco-methylthioninium bis (hydromethanesulfonate), decreases α-synuclein inclusions in a transgenic mouse model of synucleinopathy. Front .Mol. Neurosci. doi:10.3389/fnmol.2017.00447 (2018)