Collaborative MS Research Center Award
Collaborative MS Research Center Award Skirball Institute,
Paula Dore-Duffy, PhD,
Wayne State University
Robert P. Lisak, MD
Alex Gow, PhD
Harry Chugani, MD
Diane Chugani, PhD
Mark Haacke, PhD
William Brusilow, PhD
Omar Khan, MD
John Kamholz, MD, PhD
Joyce Benjamins, PhD
James Garbern, MD, PhD
Robert Skoff, PhD
Richard Needleman PhD
Gregory del Zoppo, MD
Scripps Research Institute
La Jolla, California
Joseph La Manna, PhD
Case Western Reserve University School of Medicine
Summary: Exploring bioenergetic and metabolic changes in the brain and spinal cord in MS that may hold clues to its destructive nature and provide better ways to predict and track the disease.
Details: Multiple sclerosis occurs when the immune system attacks the myelin that coats and insulates nerve fibers in the brain and spinal cord. Nerve fibers themselves also are damaged in this attack, and it is believed that this damage in particular leads to the long-term progression of disability. Despite research efforts, MS remains an unpredictable disease; it is difficult to predict or track its course in any individual.
Paula Dore-Duffy, PhD, who has a long and outstanding track record in MS research, has gathered an expert team to explore a novel method of tracking MS. They are exploring biochemical changes in tissue that may occur before evidence of the immune attack. Such changes may underlie the cause of MS and help to predict future damage.
One objective is to investigate whether metabolic abnormalities correlate with the course of MS. Specifically, certain metals such as iron and zinc play important roles in maintaining cell function and survival. Dr. Dore-Duffy has shown that levels of such metals are increased in people with MS. Mark Haacke, PhD, who is new to MS research, has developed a new imaging technique susceptibility weighted imaging that is sensitive to local iron content. The group is now following 20 people with relapsing-remitting MS for two years using this technology, and are correlating the results with disease activity and with results from an imaging technique developed by Harry Chugani, MD, and Diane Chugani, PhD.
Drs. Chugani’s technique uses PET (positron emission tomography) scanning to evaluate tryptophan as a measure of possible abnormalities of glucose metabolism. Nerve cells and myelin are highly dependent on a continuous supply of oxygen and glucose. PET scanning shows the uptake and distribution of substances within tissue, allowing researchers to observe whether defects in glucose processing plays a role in MS.
Another project focuses on damage that might be induced by hypoxic stress (reduced oxygen levels). Dr. Dore-Duffy and Alex Gow, PhD an expert in metabolic stress as it relates to myelin formation are collaborating with hypoxia/ischemia experts Gregory del Zoppo, MD, and Joseph La Manna, PhD. This group is examining the stress response to low oxygen in mice with the MS-like disease EAE. The team is engineering mice in which cells affected by hypoxia are labeled fluorescently to track their path across the blood-brain barrier in EAE.
William Brusilow, PhD, and Richard Needleman, experts in bioenergetics of mitochondrial function, are investigating whether alterations in mitochondria the part of the nerve cell responsible for energy production contribute to nerve fiber damage in MS. The team is inducing EAE in mice and analyzing mitochondrial activity at early and progressive stages of disease to determine if early changes in the mitochondria predict later damage.
Joyce Benjamins, PhD, and Robert Skoff, PhD, noted researchers in the field of myelin biology, are working with Dr. Diane Chugani to observe tryptophan metabolism in people in mice with EAE. Tryptophan, common in many foods, is an amino acid needed by the body to build proteins. Glucose processing defects may inhibit the body’s ability to metabolize tryptophan.
A wealth of experience in basic and clinical MS research is brought to the team by co-investigators Robert Lisak, MD, Omar Khan, MD, John Kamholz, MD, PhD, and James Garbern, MD, PhD.
This talented and expert collaboration is sure to yield important information that can help to predict and track disease activity in people with MS, addressing the unpredictable nature of this devastating disease.