Could a new treatment for Alzheimer’s be found in cancer drugs? That’s the question researchers at Penn State, Stanford University, and an international team of collaborators are exploring. A recent study published in the journal Science reveals the potential of repurposing a type of drug developed for cancer treatment to combat neurodegenerative diseases like Alzheimer’s.
The key lies in blocking an enzyme called indoleamine-2,3-dioxygenase 1, or IDO1. By inhibiting this enzyme, researchers were able to improve memory and brain function in models mimicking Alzheimer’s disease. This breakthrough suggests that IDO1 inhibitors, already in development for various cancer types, could be a game-changer in treating early-stage neurodegenerative diseases that currently lack preventive treatments.
Melanie McReynolds, co-author of the study and an expert in Biochemistry and Molecular Biology at Penn State, emphasizes the importance of this discovery. “The potential for IDO1 inhibitors to target and treat Alzheimer’s is significant,” she explains. “Addressing metabolic decline in neurological disorders could have far-reaching impacts on individuals, families, society, and the economy as a whole.”
Alzheimer’s disease, the most common form of dementia, affects millions of people worldwide and is expected to triple in prevalence by 2060. Current treatments focus on managing symptoms and slowing disease progression, but there are no approved therapies to combat its onset. This study offers a new approach by targeting brain metabolism to reverse the progression of the disease.
The researchers used various models to demonstrate the effectiveness of blocking IDO1 in restoring healthy glucose metabolism in brain cells known as astrocytes. These cells play a crucial role in supporting neurons and maintaining brain function. By suppressing IDO1, the researchers were able to boost metabolic support for neurons and improve their functionality.
IDO1 functions by breaking down tryptophan into a compound called kynurenine, which is part of the kynurenine pathway essential for providing cellular energy to the brain. Excessive kynurenine production by IDO1 diminishes glucose metabolism in astrocytes, impairing energy production for neurons. By inhibiting IDO1, researchers were able to enhance metabolic support for neurons and restore their function.
In addition to Alzheimer’s disease, the study suggests that IDO1 inhibition could have implications for other neurodegenerative disorders such as Parkinson’s disease dementia and tauopathies. Understanding the impact of brain metabolism on cognitive decline is crucial for developing effective treatments for these conditions.
The collaborative effort involved researchers from Penn State, Stanford University, The Salk Institute for Biological Studies, Keio University, Princeton University, University of California San Francisco, and other institutions. Funded by the Howard Hughes Medical Institute Hanna H. Gray Fellows Program Faculty Phase and the Burroughs Welcome Fund PDEP Transition to Faculty, this research sheds new light on the potential of repurposing cancer drugs for treating neurodegenerative diseases.
As the search for effective treatments for Alzheimer’s and other neurodegenerative diseases continues, the discovery of IDO1 inhibitors as a promising avenue offers hope for millions of individuals worldwide. By targeting brain metabolism, researchers are paving the way for innovative therapies that could change the course of these devastating conditions.
