Possible Cell Therapy Treatment for Alzheimer's Disease

Research from Gladstone Institutes suggests that transplanting genetically altered interneurons could improve cognitive function for Alzheimer’s disease. In Alzheimer’s disease, damage to specific neurons can alter brainwave rhythms and cause a loss of cognitive functions. Inhibitory interneurons are especially important for managing brain rhythms.

The study, published in Neuron on March 15, 2018, was funded by the Alzheimer’s Association and led by Jorge Palop, PhD, assistant investigator at the Gladstone Institutes. Palop and his team discovered therapeutic benefits associated with genetically improving interneurons and transplanting them into the brain of a mouse model of Alzheimer’s disease.

Because interneurons control complex networks between neurons, they allow signals to be sent to one another in a harmonized way. An imbalance between these two types of neurons, however, creates disharmony, which can be seen in multiple neurological and psychiatric disorders, including Alzheimer’s disease, epilepsy, schizophrenia, and autism.

Previous research done by Palop shows that the inhibitory interneurons in mouse models of Alzheimer’s do not function properly. This is because of a disturbance of the rhythms that organize the excitatory cells. These cells fail to function harmoniously, which causes an imbalance in the brain networks. This affects memory formation and can lead to epileptic activity, which is often observed in patients with Alzheimer’s disease.

Palop and his team confirmed that these improved interneurons, when transplanted into the abnormal brain of Alzheimer mice, can properly control the activity of excitatory cells and restore brain rhythms.

“We took advantage of the fact that transplanted interneurons can integrate remarkably well into new brain tissues, and that each interneuron can control thousands of excitatory neurons,” said Palop, in a Gladstone Institutes press release. “These properties make interneurons a promising therapeutic target for cognitive disorders associated with brain rhythm abnormalities and epileptic activity.”

When the scientists initially transplanted regular interneurons, they saw no beneficial effects, presumably because Alzheimer’s disease creates a toxic environment in the brain. The researchers then genetically improved the activity of inhibitory interneurons by adding a protein called Nav1.1. According to Gladstone, they discovered that the interneurons with enhanced function were able to overcome the toxic disease environment and restore brain function.

“These optimized neurons are like master conductors,” noted Palop in the release. “Even with a declining orchestra, they can restore the rhythms and harmony needed for cognitive functions.”

The institute states that these findings could eventually lead to the development of new treatment options for patients with Alzheimer’s disease.

“Besides the applications this cell engineering and transplantation approach may find in regenerative medicine, our findings support the broader concept that enhancing the function of interneurons can counteract key aspects of Alzheimer’s disease,” said Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease, in the release.

Palop and his team are currently examining if the cell therapy could be translated from mice to humans as well as working to identify drugs that could also potentially enhance the function of inhibitory interneurons.

Sources: Neuron, Gladstone Institutes