Everyone has their own medicine
A group of researchers from the University of Buffalo explained why new drugs that are successful in animal trials fail in clinical trials in patients with Alzheimer's disease.
Researchers have identified a gene variant present in 75% of the population, which is the main reason for the ineffectiveness of a group of new drugs for the treatment of Alzheimer's disease, although its effectiveness has been proven in animal studies.
The researchers write that different Alzheimer's patients have different mechanisms that determine whether this therapy will be effective.
The study has a number of limitations, and randomized double-blind studies are needed to confirm the results.
It was based on data from a ten-year longitudinal multicenter cohort study conducted by the Texas Consortium for the Research and Treatment of Alzheimer's Disease (TARCC). It involved 345 patients with Alzheimer's disease.
Proof of concept
The study confirms the hypothesis that different mechanisms work in different cases in different patients with Alzheimer's disease. Therefore, it is necessary to develop personalized treatments that will be more effective for individuals.
The CHRFAM7A gene is partially duplicated and forms a hybrid with the FAM7A gene from the acetylcholine receptor family. Together, they encode a hybrid receptor protein for the alpha7-nicotine receptor of the neurotransmitter acetylcholine involved in memory and learning.
The gene and the corresponding protein exist in the population in two variants: active (in 75%) and inactive (25%). The CHRFAM7A gene is associated with many neuropsychiatric disorders, such as schizophrenia and bipolar disorder.
Three of the four drugs currently available to treat Alzheimer's disease stimulate all acetylcholine receptors. More specific drugs for alpha-7 receptors have been developed for more than 10 years, but failed in the transition to clinical trials.
In the central nervous system, the alpha-7 receptor, among other functions, binds beta-amyloid, a protein that is a hallmark of Alzheimer's disease and which destroys neural communication.
Because the human CHRFAM7A gene was not present in animal models and screening systems used to identify drugs, 75% of Alzheimer's patients who carry this gene are less likely to respond to therapy.
The researchers compared the effects of cholinesterase inhibitors in patients who carried different variants of the CHRFAM7A gene. It is expected that people who have CHRFAM7A inactive respond better to currently available medications.
Neurons in Alzheimer's disease are vulnerable to alpha-7 expression, and this is a possible reason for their rapid death. This work confirms that alpha-7 is an important therapeutic target for the treatment of Alzheimer's disease, but the right model - the human model - should be used in the development of new drugs and their research.
According to the results, an individual approach to each patient is required, depending on the variants of the CHRFAM7A gene. One drug can work in 25% of patients, and the other in 75%, and it is important to take this into account.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to University at Buffalo: First clinical proof that genotypes determine if Alzheimer's drugs will work: Researchers' insights into a target that succeeded in animals but failed in humans reveal a new paradigm for screening Alzheimer's drugs.