July 12, 2024

Experimental Drug Slows Tau Protein Aggregation and Improves Cognitive Function in Monkeys

Researchers have made a significant breakthrough in the development of a potential treatment for Alzheimer’s disease (AD). A new experimental drug has been shown to slow down the aggregation of the tau protein, a key contributor to the development of neurofibrillary tangles commonly seen in AD patients. The drug has also been found to improve cognitive functioning in experimental monkeys. These findings present a promising step towards the development of an effective treatment for humans.

AD is a neurodegenerative disease characterized by the accumulation of harmful proteins called amyloid beta and tau. Current treatment methods mainly focus on removing these proteins; however, by the time they have accumulated, significant damage to neurons may have already occurred. In healthy brains, the tau protein plays a vital role in maintaining the structural stability of microtubules, which are essential for neuronal function. In AD, tau becomes hyperphosphorylated, leading to its aggregation into neurofibrillary tangles, a hallmark of the disease. Research suggests that inflammation in the aging brain contributes to this abnormal tau phosphorylation.

The research team, led by Amy Arnsten, aimed to target the brain enzyme glutamate carboxypeptidase II (GCPII). GCPII expression increases with inflammation and impairs the protective effects of the metabotropic glutamate receptor 3 (mGluR), a receptor involved in higher cognitive functions. The researchers tested an inhibitor of GCPII called 2-MPPA, which was synthesized by the Johns Hopkins Drug Discovery program. The drug was administered daily for a period of six months to aged rhesus macaque monkeys that naturally exhibited GCPII and tau pathology.

The results of the study were highly promising. The team found that 2-MPPA significantly reduced the hyperphosphorylation of tau in the experimental monkeys. Furthermore, the monkeys treated with the drug showed improvements in cognitive function. Notably, no apparent side effects were observed during the course of the study. These findings highlight the potential of GCPII inhibition as a therapeutic approach to reduce the risk of sporadic AD caused by inflammation.

“This research presents a novel mechanism of protection that is different from other approaches undertaken so far,” said Amy Arnsten, the corresponding author of the study. The development of a drug that can be used in humans is the next crucial step in this groundbreaking research.

The findings of this study offer hope to the millions of individuals worldwide affected by AD. By targeting the hyperphosphorylation of tau and reducing inflammation, this experimental drug could potentially slow down or prevent the neurodegenerative process associated with the disease. However, further research and clinical trials are necessary to determine the drug’s safety and efficacy in humans. Nevertheless, this discovery represents a significant advancement in the quest for an effective treatment for AD.

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1. Source: Coherent Market Insights, Public sources, Desk research
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