Alzheimer's disease (AD) is the most common dementia worldwide, characterized by the presence of senile amyloid-beta (Aβ) plaques in the brain where, in particular, the most aggressively aggregating isoform Aβ42 accumulates. Despite numerous trials in animal models, almost all current therapies against AD have failed in clinical trials, and the few approved treatments only offer modest symptomatic relief and are unable to alter the course of the disease. None of the available treatments prevents, halts, or reverses the neurodegenerative process induced by Aβ42 toxicity. New compounds that can decrease Aβ42-induced toxicity, reduce plaque formation, therefore, are of critical requirement.

3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-carbonyl]amino]propanoic acid (THICAPA) is a new drug candidate for which a single pharmacological activity is targeted on Aβ42. THICAPA has two functions: it binds onto Aβ42 to reduce fibrillary aggregation and improves cell viability in neuronal cellular models of Aβ42. In contrast to current treatments, THICAPA protects neuronal cells from Aβ42-induced toxicity. In flies expressing Aβ42, THICAPA displayed significant rescue of the rough eye phenotype, lifespan and improved motor function. This mechanism downregulated immune response pathways, pointing towards a multifaceted approach to mitigating Aβ42 toxicity.

The innovation behind this project is THICAPA, a new and promising compound that targets the root causes of Alzheimer’s disease (AD), not just the symptoms. THICAPA works by binding to the toxic Aβ42 protein, reducing the build-up of harmful plaques in the brain that lead to memory loss and brain damage. Unlike current treatments, THICAPA protects brain cells, improves their function, and may slow or stop the disease from getting worse. It also helps reduce inflammation and shifts the body’s processing of proteins in a way that lowers the production of Aβ42. In lab tests, THICAPA improved brain cell survival and reduced damage caused by Aβ42. In animal models, it extended lifespan, improved movement, and reduced signs of the disease. These results show that THICAPA has the potential to become the first treatment that could actually slow or change the course of Alzheimer’s, offering real hope to millions of patients.