Potential new treatment pathway for peripheral neuropathy

Potential new treatment pathway for peripheral neuropathy
Credit: Google and JCI

Research groups in US and Canada have  identified a molecular pathway that , when blocked , promotes sensory neuron growth and prevents or reverses peripheral neuropathy in cell and rodent models of type 1 and 2 diabetes, chemotherapy-induced neuropathy and HIV.

Peripheral neuropathy (PR) is a condition resulting from damage to the peripheral nervous system-  the vast communications network that transmits information between the central nervous system (brain and spinal cord) and the rest of the body. Symptoms range from numbness, tingling and muscle weakness to severe pain, paralysis and organ dysfunction. An estimated 20 million Americans have some form of PR, which can be a symptom of many diseases, including diabetes and HIV, or a side effect of some chemotherapies.

Previous research has described at least some of the fundamental processes involved in healthy, on-going peripheral nerve growth regeneration, including the critical role of mitochondria – cellular organelles that produce adenosine triphosphate (ATP), the energy-carrying molecule found in all cells that is vital to driving nerve recovery after injury.

The researchers looked for  key molecules and mechanisms used in sensory neuron growth and regrowth. In particular, they noted that the outgrowth of neurites- projections from a neuronal cell body that connect it to other neurons-  was constrained by activation of muscarinic acetylcholine receptors. This was surprising, because acetylcholine is a neurotransmitter usually associated with activation of cells.

With identification of this signaling pathway, the scientists suggest it is now possible to investigate the utility of anti-muscarinic drugs already approved for use in other conditions as a new treatment for peripheral neuropathy.

"This is encouraging because the safety profile of anti-muscarinic drugs is well-characterized, with more than 20 years of clinical application for a variety of indications in Europe," said the senior study author. "The novel therapeutic application of anti-muscarinic antagonists suggested by our studies could potentially translate relatively rapidly to clinical use”.