Immungenetics AG is conducting a Phase 2 proof-of-concept clinical trial to investigate whether thiethylperazine — a treatment for nausea and vomiting in use since the 1960s — might help people with Alzheimer’s disease by working to slow or stop the early events that underlie disease progression.
Thiethylperazine, sold for years under the brand name Torecan, was approved both in Europe and the U.S. to treat nausea and vomiting, so it has an established safety profile. The new clinical trial by the German company — getting underway in Europe (registry No. 2014-000870-20) — aims to confirm an entirely new mechanism of action for thiethylperazine that raises its potential as a first-in-class Alzheimer’s treatment.
Preclinical studies have shown that thiethylperazine acts on transporter proteins localized at the blood-brain barrier — a protective membrane that separates the brain from blood circulating systemwide. In this early work, it was seen to activate these transporters to promote the removal from the brain of the toxic clumps of beta-amyloid protein via blood circulation.
Researchers believe that inefficient clearing of beta-amyloid aggregates is a key event triggering Alzheimer’s disease, more so than overproduction of beta-amyloid protein.
The trial, called DrainAD, was selected by the scientific advisory board of the nonprofit GiveToCure as a highly promising Alzheimer’s study. Researchers are recruiting up to 60 people, between the ages of 55 and 75, a mix of Alzheimer’s patients at the early-to-mild dementia phase and healthy volunteers as controls.
The first group of about seven patients and controls are being treated for four consecutive days with a daily dose of 26 mg or 52 mg of thiethylperazine, administered orally as a tablet. Researchers will use data collected to determine thiethylperazine’s safety and tolerability and, most importantly, to evaluate its ability to sweep beta-amyloid from the brain into the bloodstream.
The trial also includes a sub-study where researchers aim to develop and establish, for the first time, a blood-based biomarker assay for diagnosing early Alzheimer’s.
“The first part of the study will confirm the mechanism of action and determine the diagnostic use. There is an urgent need for a blood-based diagnostic method able to identify people at risk of Alzheimer’s disease very early in the process. At a certain age, this test should be part of every regular blood screening. Lumbar puncture and PET scans are advanced and costly procedures that can be selectively conducted afterwards,” said Antonio Martinez Arbizu, Immungenetics’ chief executive officer, in a news release.
The study’s first part will be led by a biomarker expert, Jens Wiltfang, of the University of Göttingen who is also deputy coordinator of clinical research at the European Alzheimer’s Disease Consortium, Arbizu added.
Next, a second group will be treated for 54 days with 26 mg thiethylperazine daily and will be closely monitored during a follow-up period. At this stage, researchers will assess if treated patients show improvements in cognition. Lutz Frölich, head of geriatric psychology at the University Heidelberg-Mannheim, will lead this part of the study.
“In the second part of the study … we will assess cognitive benefits after a three months’ administration of thiethylperazine and determine its therapeutic benefits,” Arbizu said.
Drain AD is is partly funded by the German Federal Ministry of Research within the country’s Neuroallianz programme.