Scientists have developed a new technique that could eventually lead to new potential treatments for Alzheimer’s disease. The team investigated a compound that breaks down a protein associated with the disease, with tests in mice improving symptoms.
A protein called p38 has previously been linked to the development of Alzheimer’s, so it’s not surprising that scientists have investigated it as a drug target for the disease. Drug candidates that inhibit p38 have gone through several phases of clinical trials, but unfortunately demonstrated limited effectiveness and unwanted side effects.
So for the new study, researchers in South Korea switched focus to a different form of the protein. When p38 undergoes a modification process called phosphorylation, it becomes an active form of the protein known as p-p38. By targeting this version instead, the treatment could potentially be made more specific, reducing side effects and hopefully boosting efficacy.
After screening a range of compounds that could target p-p38, the team identified one called PRZ-18002, which was effective in not just inhibiting the protein but degrading it. Importantly, it was very selective for p-p38 alone – the team tested it against 96 similar protein kinases, including p38, and found that it stayed on target.
In tests on mouse models of Alzheimer’s, the team found that PRZ-18002 successfully downregulated the p38 pathway. That improved the animals’ cognitive abilities, such as spatial reasoning, and reduced brain chemistry related to the disease, like the accumulation of amyloid-beta plaques.
Of course, it’s still quite early days for this research. Results in mice don’t always carry across to humans, and this technique could still fail in clinical trials like its predecessors. But it’s an intriguing new avenue nonetheless.
The research was published in the journal ACS Central Science.
Source: American Chemical Society