A new piece of the puzzle
Two years after the discovery of a way to neutralize an uncontrolled protein associated with Alzheimer's disease, Emeritus professor at the University of Alberta and neurologist Jack Jamandas discovered a new piece of the Alzheimer's puzzle, bringing science closer to the victory of this disease.
Jamandas and his group discovered two short peptides that, when administered to mice with Alzheimer's disease daily for five weeks, significantly improved their memory. Experimental treatment also reduced the severity of some of the changes in the brain associated with the disease.
In mice that received medications, a decrease in the accumulation of amyloid plaques and a decrease in brain inflammation was found, which proves not only an improvement in the clinical condition of mice, but also a decrease in signs of brain pathology in Alzheimer's disease.
Based on previous research
This discovery is based on previous work on the compound AC253, which can block the toxic effect of the beta-amyloid protein – one of the main causes of Alzheimer's disease. Beta-amyloid is often found in large quantities in the brains of patients with the disease. AC253 blocks the amylin protein receptor.
And although AC253 has been shown to prevent the accumulation of beta-amyloid, it was not able to penetrate the brain in sufficient quantities and was rapidly metabolized when injected into the bloodstream. Therefore, treatment using AC253 required large amounts of the compound. This is expensive and increases the risk of developing an unwanted immune response to treatment. Turning AC253 from an injectable drug into a tablet could solve metabolic problems and increase efficiency, but the structure of AC253 is too complex to make it an effective oral drug.
Jamandas decided to split AC253 into its component parts and try to create smaller peptide strands that block the accumulation of beta-amyloid in the same way as AC253. As a result of a series of tests using genetically modified mice with an Alzheimer's disease model, the group found the two shortest fragments of AC253 that reproduced the preventive and restorative effects of a larger peptide.
A new drug
Having identified short peptides, Jamandas and his colleagues used computer modeling using artificial intelligence to create a low-molecular-weight drug. The work is currently ongoing.
The researchers are focused on producing an optimized oral version of the drug so that human clinical trials can begin. It is worth adding that low-molecular-weight drugs are preferable not only for patients, because they can be taken as tablets and they reach the brain more easily, but also for pharmaceutical companies, because they are cheaper to produce.
Article by R. Soudy et al. Short amylin receptor antagonist peptides improve memory deficits in Alzheimer's disease mouse model published in the journal Scientific Reports.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Folio: New piece of Alzheimer's puzzle found.