Researchers at the University of Illinois College of Medicine Rockford found promising results in their search for a treatment to stop nerve cell degeneration that happens in some types of disorders, such as hereditary spastic paraplegia and Parkinson’s disease, which can cause significant disability.
The research, published in the journal Brain, was led by Xue-Jun Li, PhD, co-director of the UICOMR Regenerative Medicine and Disabilities Laboratory and the Michael A. Werckle Endowed Professor in the Department of Biomedical Sciences.
The study looked at how the long axons that carry messages between nerve cells in the brain can break down, which leads to increasingly worse tightening of the leg muscles leading to imbalance and eventually paralysis, in addition to other symptoms.
Previous studies that used animal models to study the causes of the nerve cell degradation showed it may be a problem with the mitochondria, the powerhouse that drives the cells, that leads to the axons breaking down or not growing long enough. Studying human nerve cells is difficult, but Dr. Li’s team, including Zhenyu Chen, PhD, Eric Chai, MS, and Yongchao Mou, PhD, were able to use human cells that they transformed into stem cells and then modified to become nerve cells with the genetic disorder for a particular type of hereditary spastic paraplegia.
“What we found was that the mitochondria in these cells were breaking apart, what we call mitochondrial fission, and that caused the axons to be shorter and less effective at carrying messages to the brain,” explains Li. “We then looked at whether a particular agent would change the way the nerve cells function — and it did. It inhibited the mitochondrial fission and let the nerve cells grow normally and also stopped further damage.”
What this means for the thousands of people affected by this type of genetic disorder, is that this agent, a particular chain of amino acids called a peptide, could prove to be useful for a drug or other therapy to stop the nerve cells from becoming damaged or reverse the course of the damage. The researchers also suggest using gene therapy could prevent the mitochondrial damage, providing another strategy to reverse the nerve damage.
The research was supported by the National Institute of Neurological Disorders And Stroke of the National Institutes of Health and done in collaboration with Craig Blackstone, MD, PhD, and Ricardo Roda, MD, PhD, of the NIH Cell Biology Section.
The Regenerative Medicine and Disability Laboratory is part of the Department of Biomedical Sciences at the University of Illinois College of Medicine Rockford. Established through generous support of the Blazer Foundation, this lab is headed by Dr. Xue-Jun Li and Dr. Mathew T. Mathew who focus on fighting human motor neuron diseases and improving the integration of metal implants into the surrounding bone tissue, respectively. By combining stem cell biology, bioengineering, biomaterials, system biology, pharmacology and medicine, research in the RMDR Lab aims to identify therapeutic agents, novel biomaterials and innovative approaches to improve clinical practice to provide better health care to patients with disabilities.
Research reported in this publication was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number R21NS109837 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.