Hydromethylthionine (TauRx Therapeutics, Aberdeen, Scotland) treatment resulted in statistically significant decreases in clinical decline and brain atrophy in people with behavioral variant frontotemporal dementia (bvFTD). These results were published in The Journal of Alzheimer's Disease.
Pharmacokinetic analysis was performed on blood samples from 176 participants at baseline and 12 months. Using a new assay, the researchers found that the effects of hydromethylthionine at the 8 mg/day dose correlated with plasma concentration of the drug. Even with this low dose and concentration, clinical decline and brain atrophy was reduced by about half over 12 months compared with people who had minimal blood concentration. The high dose of 200 mg/day gave no additional benefit over the 8 mg/day dose. These analyses suggest that a dose of about 30 mg/day would be optimal for treating bvFTD and could reduce the rate of disease progression even more.
Hydromethylthionine blocks abnormal aggregation in the brain of the proteins (tau protein and TDP-43 protein) linked to over 80% of bvFTD. In this global phase 3 clinical trial, 220 participants who had bvFTD, as defined by international criteria, and also brain MRI evidence of were treated with 200 mg/day or 8 mg/day of hydromethylthionine. The lower dose was intended as a control to mask the discoloration of urine that can sometimes occur with hydroxymethylthionine. As in the recently reported hydromethylthionine trials in AD, there was no difference between the high dose and the low dose on any of the clinical outcomes in the trial.
The study analysis showed that the concentration-response profile in bvFTD is similar to that recently reported in AD. The present results support the idea that hydromethylthionine works in a similar way in both AD and bvFTD. Pharmacokinetic analysis of data from this study (NCT00515333) also show that these results were dependent on plasma concentration of the drug.
Claude Wischik, professor of Aberdeen University and executive chairman of TauRx Therapeutics commented: "These new results, coming as they do on top of the similar results we recently reported in AD, provide independent confirmation that hydromethylthionine has important pharmacological activity on brain structure and function in neurodegenerative diseases caused by abnormal protein aggregation. The results in bvFTD now give us the confidence to progress with a further confirmatory trial which we hope to begin recruiting early next year. A confirmatory trial in AD is already underway."
Professor Serge Gauthier, director of the AD Research Unit, McGill Center for Studies in Aging, commented: "Although much rarer than AD, bvFTD is a severely debilitating and rapidly progressive disease that is extremely distressing for families. The possibility of a new drug on the horizon in the form of hydromethylthionine for the first time offers a real hope for those affected."
Zehra Farzal, MD; Guillaume Lamotte MD, MSc; Elizabeth Mundel, MD; Laxman B. Bahroo, DO; and Fernando L. Pagan, MD
Barbara C. Jobst, MD