Combs receives grant from the Michael J. Fox Foundation

Abstract

GRAND FORKS, N.D. — Professor Colin Combs, Ph.D., in the Department of Basic Sciences at the University of North Dakota School of Medicine and Health Sciences has been awarded $88,200 from the Michael J. Fox Foundation for Parkinson\u27s Research. The Rapid Response Innovation grant is for a project titled Defining the Contribution of Neuroinflammation to Parkinson\u27s Disease in Humanized Immune System Mice. Inflammation is a defensive response by the body\u27s immune system to an injury, infection, or allergy. In the central nervous system — the brain and spinal cord — the immune response is performed by specialized cells called microglia, which patrol the central nervous system and clear it of cellular debris and dead neurons. Overactivation of microglia during the immune response has been associated with neuroinflammation and the cellular degeneration that occurs in Parkinson\u27s disease. This suggests that brain inflammation may influence the course of disease and that anti-inflammatory therapies might be useful, said Combs. However, it is difficult to answer this question with the typical lab approach of using rodents to study the disease since the rodent immune system may differ quite a lot from that of a human. Combs and his lab team will overcome this limitation by using a unique model with a humanized immune system to test whether specific inflammatory changes in the brain contribute to degeneration during disease. The mice that Combs will use in his study have been humanized with stem cells derived from the bone marrow of human adults. Adult bone marrow stem cells form all the types of blood cells in the body. The mice have a compromised immune system already, said Combs. The adult human stem cells in the mice subsequently develop into mature immune cells essentially replacing the mice\u27s deficient immune cells. This allows laboratories like ours to ask questions regarding how the human immune system works although the model remains a mouse. Laboratory mice, Mus musculus to scientists, have been bred for generations to be genetically identical. Because mice are genetically and physiologically similar to humans (mice and humans share 95 percent of their genes), scientists find mice to be incredibly valuable experimental tools for research into the genetic basis of neurodegenerative diseases such as Alzheimer\u27s and Parkinson\u27s. Scientists have developed a vast knowledge bank of lab mouse DNA that they can use to study how the effect of changes in specific genes may underlie certain diseases. An immediate next step will be to verify that the immune changes in the mice also occur in human patients, said Combs. We will then need to check whether broad anti-inflammatory drugs or targeted immunomodulatory drugs are most effective in slowing disease in the mice to provide candidate drugs for human trials. The Michael J. Fox Foundation, which was founded in 2000, is the world\u27s largest nonprofit funder of Parkinson\u27s disease research. With no endowment, MJFF rapidly deploys non-dilutive capital as well as intellectual and other resources with one goal in mind: to accelerate development of improved therapies and, ultimately, a cure for those living with Parkinson\u27s today. Their internal team of experts and ever-evolving funding strategy allow the foundation to invest in research that will have the greatest impact and potential to change patients\u27 lives. More information about Combs\u27 project and the Michael J. Fox Foundation can be found at https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=1357