Thiethylperazine (TEP) is one of the first drugs to be repurposed andtested in a clinical trial involving humans with AD that target the underlyingcause of the disease. TEP is an activator but not a substrate of theABCC1 transporter and causes increased ABCC1 transporter activity. Preclinicalstudies suggest that TEP reduces Abeta levels and amyloid plaque burden in theCNS via activation of ABCC1 transporter. Based on strong preclinical data,Immungenetics hypothesizes that TEP will generate a clear difference in ADspecific plasma Abeta biomarkers between AD patients and healthy controls throughtriggering the efflux of Abeta peptides from the brain into the blood.
Founded in 2009, Immungenetics AG is an early stage biotechnology academic spin-off that seeks to commercialize therapeutic and diagnostic breakthroughs from university research. One of Immungenetics’ developmental areas of interest concerns diagnostic assays and drug candidates for neurodegenerative diseases with special focus on the blood-brain-barrier (BBB).
The Principal Investigator Professor Lutz Frölich, M.D., heads the Department of Geriatric Psychiatry at the Central Institute of Health, University of Heidelberg, Mannheim, Germany has over 20 years’ experience in AD research and clinical trials and has published over 200 original data and review articles in peer-reviewed journals. He has been an investigator and Principal Investigator in more than 30 clinical trials. His major research interests are clinical dementia research and the development, evaluation of innovative therapies in AD.
TEP reduces the plaque burden in the central nervous system. Based on strong preclinical data, Immungenetics hypothesizes that TEP will generate a clear difference in AD biomarkers by flushing those plaque molecules from the brain into the blood.
This is a Phase IIa Trial and will last 2 years. It is studying 60 patients newly diagnosed with early dementia due to Alzheimer’s Disease (AD) (anticipates 14% drop-out rate) and each patient is to undergo a screening and treatment phase of approximately 12 weeks.
If TEP is safe, why do we need a clinical trial? Why can’t my doctor just prescribe it right now?
Repurposed drugs significantly accelerate the clinical trial timelines but it doesn’t eliminate the need for clinical trials altogether for the new indication. Clinical trials are required to determine the correct dosage, frequency, and most effective way to administer the drug for Alzheimer’s Disease patients . In addition to testing the overall efficacy of the compound, testing these parameters are just as important in developing an effective drug regimen.
What are the side effects of TEP?
In previous clinical trials of TEP the only side effects observed were drug-induced extrapyramidal symptoms (EPS). (The extrapyramidal system is a neural network that is part of the motor system that causes involuntary reflexes and movement.) These symptoms have been shown to be temporal and reversible after discontinuation of TEP. In the proposed study the researchers intend to use dosages far below those used in the aforementioned trials, which will which dramatically reduces the probability EPS in the study patients
Present strategies for the treatment of AD offer minimal symptomatic relief without addressing the underlying cause.
Preclinical investigations suggest it can reverse, or at least significantly slow AD progression by draining a certain molecule, which is a main component in brain plaque, from the brain. Previous studies have found that it may not be the production of these plaque-inducing molecules that triggers the development of AD, but the ability for the brain to clear, or drain them. This suggests that a treatment centered on transporting those toxins from the brain (instead of focusing on how to prevent their production) may play a fundamental role in the pathogenesis of AD and could be a target for novel treatment.
TEP is a very well-known substance which has been in the market as an anti-emetic since 1961 with a well understood pharmacologic background and promising data on safety and known side effects.