Researchers at the University of California, San Diego School of Medicine and Cenna Biosciences have likely found a breakthough that could help stop Alzheimer’s disease from progressing. Researchers have found compounds that will stop the production of beta amyloid peptides, but they found the compounds using mice and not humans.
If researchers can find the compounds in humans, it could mean a new treatment option for Alzheimer’s patients, which would end up stopping the disease in its tracks. The compound that sounds the most promising is P8, which is a specific peptide that researchers believe could be given to people at the highest risk of developing Alzheimer’s disease. The study from the researchers was published in PLOS ONE, and it also could stop the disease before dementia occurs. Since the compound has a very specific action associated with it, there is also a decreased chance of side effects.
The lead author of the study, Nazeen Dewji, is an associate adjust professor in the Department of Medicine, and says that this is a new approach that has not been used before in terms of targeting the beta amyloid. When the plaque of the beta amyloid builds up, it can end up causing brain damage that is irreversible, and this impairs motor and cognitive functions. A lot of the same impairments from the plaque build up is associated with Alzheimer’s disease, and Alzheimer’s is responsible for between 60 to 80 percent of dementia cases in the United States.
The bigger protein involved is the amyloid precursor protein, and several different drugs have been produced to cleave the beta amyloid from the amyloid precursor protein. The drugs are targeting the enzymes, but all of these drugs have failed overall when it comes to the clinical trials. The problem with the drugs that have been produced is that they don’t just impact the amyloid precursor protein, which means the drugs are harming the good proteins too. When you modify how the cleaving process works in cells, it ends up altering more than what you are trying to target, especially when you are working on the enzymes.
In terms of P8, it is different because it does not work on the enzymes, and it only binds to the amyloid precursor protein. This is important because binding to the amyloid precursor protein stops it before it can get to the next stage of progession, which is the amyloid peptides. The binding that happens between amyloid precursor protein and the P8 was measured in this study by imaging and biophysical methods. Presenilin 1 is a membrane protein that works with the amyloid precursor protein to help advance it to the beta amyloid, and this is how the compounds are derived.
The researches did cell culture experiments as well as experimented on mice, which were specifically engineered to secrete high levels of human beta amyloid from an early age. The experiments were able to show that a two-week treatment program with P8 or a similar compound known as P4, showed about a 50 percent decrease in the amount of plaque build-up. In terms of what this means, if this can be produced in humans, it can stop the production of the beta amyloid very early on in the Alzheimer’s disease, and it’s a very specific treatment that does not harm other proteins or cells.
Dewji said in a statement, “Our approach is different, specific and interferes with only the reaction that produces beta amyloid, as opposed to drugs that target the enzymes responsible for its cleavage from APP, which can affect multiple reactions in cells.” The hope is that this result can be reproduced in the human population, and through clinical trials and experiments, a drug can be developed to mimic this behavior. If researchers can fine tune this compound, then people will be able to stop Alzheimer’s disease before even the most common symptoms develop, and it could prolong life expectancies of millions suffering with the progressive disease.
There is also a hope that this treatment can help prevent the disease in the first place, especially if given to the high-risk groups before the typical age of Alzheimer’s disease. If someone has a family history of Alzheimer’s disease, then this compound could be given to them years before the symptoms of the disease would show up, and this could help stop the plaque before it really even begins. In terms of how long until a drug would be available, it depends upon how long it takes researchers to develop the human version, and then quite a few human trials would need to be performed in order to determine the safety and efficacy of the drug before it could be marketed to consumers.