Thiethylperazine, sold for years under the brand name Torecan to relieve nausea and vomiting, is currently being investigated as a potential Alzheimer’s disease therapy by Immunogenetics. Its effect and safety profile in Alzheimer’s disease patients is not yet known.

How thiethylperazine works

Alzheimer’s disease is a progressive neurodegenerative disorder. It is characterized by the formation of structures called amyloid plaques and tau tangles in the brain, leading to nerve cell death and progressive loss of memory and cognitive function. The amyloid plaques are clumps of amyloid beta (Aβ) protein fragments, which fail to be removed from the brain.

Thiethylperazine is a small molecule drug that can activate a protein called MRP1 in the brain. MRP1, encoded by the gene ABCC1, is one of a number of “ABC transporters” present at the blood-brain barrier. These transporters are part of the tightly controlled system to move substances in and out of the brain. It is thought that through the increased activation of MRP1, thiethylperazine can promote the removal of the toxic Aβ to potentially reduce the damage it causes to the nerve cells.

Results of pre-clinical research published in the Journal of Clinical Investigation have shown that administering thiethylperazine to a mouse model of Alzheimer’s disease caused a significant decrease in Aβ levels in the brain.

Thiethylperazine in clinical trials

Immunogenetics AG initiated a proof-of-concept, open-label and two-part Phase 2 clinical trial, called DrainAD (EudraCT number: 2014-000870-20), to assess the effect of thiethylperazine in people with early Alzheimer’s disease. The trial aims to determine the safety profile of the treatment in Alzheimer’s patients compared to healthy volunteers as controls.

An estimated 60 patients with early to mild dementia caused by Alzheimer’s will be recruited in Germany. The trial’s first part will assess the effect of either 26 mg or 52 mg of thiethylperazine administered daily as an oral tablet for about one week in a small group of patients and controls. The second part will involve a larger number of people given 26 mg of thiethylperazine daily for about two months.

The trial will assess the level of Aβ clearance from the brain and into the bloodstream for its removal, as well as the changes in cognition potentially due to thiethylperazine. Participants will be monitored for adverse events throughout the trial and during a follow-up period.

Other information

Torecan has an established safety profile in healthy patients, and the most common side effects it causes are dizziness and drowsiness.


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