A recent study by researchers at Penn State, Stanford University, and an international team of collaborators has found that a type of drug developed for treating cancer could potentially be repurposed as a new treatment for neurodegenerative diseases such as Alzheimer’s. By blocking a specific enzyme called IDO1, the researchers were able to rescue memory and brain function in models that mimic Alzheimer’s disease. This discovery suggests that IDO1 inhibitors, which are currently being developed as a treatment for various types of cancer, could be used to target and treat the early stages of neurodegenerative diseases, providing hope for chronic conditions that lack preventative treatments.
Alzheimer’s disease, the most common type of dementia, affects parts of the brain that control thought, memory, and language. With the prevalence of Alzheimer’s expected to triple by 2060, finding new treatments for the disease is crucial. Inhibiting the enzyme IDO1, particularly with compounds that have been previously investigated in human clinical trials for cancer, could potentially protect the brain from damage caused by aging and neurodegeneration. This breakthrough could have significant implications for aging populations, impacting not only those diagnosed with neurodegenerative diseases but also their families, society, and the economy.
Current treatments for Alzheimer’s disease focus on managing symptoms and slowing progression by targeting the build-up of amyloid and tau plaques in the brain. However, there are no approved treatments for combating the onset of the disease. By targeting the brain’s metabolism and restoring healthy glucose metabolism through IDO1 inhibition, researchers were able to demonstrate that it is possible to not only slow but reverse the progression of Alzheimer’s disease. This approach addresses a potential underlying issue with the brain’s functioning, providing a new avenue for treating neurodegenerative diseases.
IDO1 is an enzyme that breaks down tryptophan into a compound called kynurenine, which plays a critical role in how the body provides cellular energy to the brain through the kynurenine pathway. By suppressing IDO1, researchers were able to increase metabolic support for neurons and restore their ability to function, ultimately impacting cognitive decline associated with neurodegenerative diseases. The study utilized various models of Alzheimer’s pathology, including amyloid or tau accumulation, and found that blocking IDO1 had protective effects across different types of pathologies, suggesting its relevance in other neurodegenerative disorders.
The study’s findings could have implications beyond Alzheimer’s disease, potentially extending to other neurodegenerative disorders such as Parkinson’s disease and tauopathies. By understanding how the brain’s metabolism is impacted with neurodegeneration, researchers hope to develop new treatments that target the underlying mechanisms of cognitive decline. With the brain’s reliance on glucose for metabolism and energy production, restoring the brain’s ability to effectively use glucose could lead to significant improvements in cognitive function for patients with neurodegenerative diseases. Collaborative research efforts have shed light on the potential of repurposing existing drugs for cancer treatment to address the complex challenges of neurodegenerative disorders.
Overall, the study highlights the promising potential of repurposing IDO1 inhibitors developed for cancer treatment as a new approach to treating neurodegenerative diseases such as Alzheimer’s. By targeting the brain’s metabolism and restoring healthy glucose metabolism in astrocytes, researchers were able to reverse cognitive decline in preclinical models. This breakthrough in understanding the role of IDO1 in controlling brain metabolism offers new possibilities for developing treatments that could potentially slow or reverse the progression of neurodegenerative diseases, providing hope for millions of individuals affected by these chronic conditions.
