Read more

January 17, 2020
2 min read
Save

Hydromethylthionine impacts brain function in patients with Alzheimer’s

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Hydromethylthionine, a potent tau aggregation inhibitor, showed pharmacological activity on brain structure and function as both monotherapy and as an add-on to symptomatic treatment in certain patients with Alzheimer’s disease, according to a post hoc pharmacokinetic analysis of phase 3 study results.

Perspective from Heather Snyder, PhD

Researchers noted that the only currently approved treatments for AD are symptomatic. Despite any small therapeutic benefit derived from treatments like acetylcholinesterase inhibitors and memantine, patients continue to decline at the untreated rate.

“From 2002 to 2012, there were 289 clinical trials at phase 2 or phase 3, with an overall failure rate of 99.6%, and a further 19 trial failures since 2012 targeting various aspects of pathological processing of amyloid-beta,” Bjoern O. Schelter, a professor at the University of Aberdeen in the United Kingdom, and colleagues wrote.

The most advanced late-stage program targeting tau aggregation involves hydromethylthionine, they said.

Older adult looking confused 
Hydromethylthionine, a potent tau aggregation inhibitor, showed pharmacological activity on brain structure and function as both monotherapy and as an add-on to symptomatic treatment in certain patients with Alzheimer’s disease, according to a post hoc pharmacokinetic analysis of phase 3 study results.

Source:Adobe

Researchers noted that two previous phase 3 trials involving 1,686 patients with AD showed no differences between daily doses of 150 mg to 250 mg hydromethylthionine and 8 mg daily, intended as a control. In the present study, researchers used a sensitive plasma assay for hydromethylthionine using samples from 1,162 of the earlier trials’ participants.

Researchers found that using a threshold based on the lower limit of quantitation of the assay on day 1, there were “highly significant differences” in brain atrophy and cognitive decline among patients with plasma levels above the threshold plasma levels — both for monotherapy and add-on therapy. However, Plasma concentrations ranging from 4 ng/mL to 21 ng/mL, associated with the higher doses, did not confer additional benefit.

Claude Wischik
Claude M. Wischik

Claude M. Wischik, co-founder and CEO of TauRx Therapeutics in Singapore and a study co-author, said in an interview that the findings show that hydromethylthionine has some pharmacological impact.

“There is a steep concentration-response relationship between plasma levels of hydromethylthionine and treatment effects on cognitive decline and brain atrophy at the low dose of 8 mg per day,” he said. “The same concentration-response profile is seen whether patients take hydromethylthionine alone or as an add-on to symptomatic treatments. But the maximum treatment effect is reduced by half when the drug as taken as add-on.”

Based on the evidence, hydromethylthionine’s maximum treatment benefit will likely be 16 mg daily and as a monotherapy, Schelter and colleagues wrote. They added that a placebo-controlled trial in patients with mild/moderate AD is underway to test the efficacy of that dose. – by Janel Miller

Disclosures : The authors and report no relevant financial disclosures.