Drug Combination Creates New Neurons From Neighboring Cells

Neurons do not regenerate after brain damage because they don’t divide, which is a big problem for brain repair; glial cells, in contrast gather around damaged brain tissue and can proliferate after brain injury. Penn State Professor Gong Chen and Verne M. Willaman suggest turning glial cells into neurons may be the best way to restore lost neuronal functions.

A sequence of nine molecules in previous research were described as directly converting human glial cells into neurons, however numbers of molecules and specific sequencing required for reprogramming complicated transition to clinical treatment. This study examines various numbers and combinations of molecules to identify a streamlined approach to reprogramming of astrocytes glial cells into neurons.

Jiu-Chao Yin say they identified the most efficient chemical formula among the drug combinations tested by using four molecules that modulate four critical signaling pathways in human astrocytes, efficiently being able to turn as many as 70% of human astrocytes into functional neurons; resulting chemically converted neurons survive more than seven months in culture dishes, forming robust neural networks and sending chemical and electrical signals to each other.

When three molecules are used rather than four also results in the conversion, but the rate drops by around 20%; using only one of the molecules did not induce conversion.

Previously the team developed a gene therapy technology to convert astrocytes into functional neurons, however due to excessive cost of gene therapy the team has been pursuing more economical approaches to convert glial cells into neurons. Gene therapy delivery systems are more complex requiring injections of viral particles into the body, smaller molecules in the new approach can be chemically synthesized and packaged into a pill. A pill containing small molecules could be distributed around the world to even reach rural areas without advanced healthcare systems to regenerate new neurons and restore lost learning and memory capabilities.

Many technical issues are need to be resolved before a drug can be created, including specifics of drug packaging and delivery, according to the team; and potential side effects of this approach will be investigated in future studies to further develop the safest drug. The team remains confident that their combination of molecules has promising implications for drug therapies to treat neurological disorders.