Microtubule Abnormalities Underlying Gulf War Illness in Neurons from Human-Induced Pluripotent Cells
Abstract
Gulf War Illness (GWI) is a condition suffered by at least 25 percent of the nearly 700,000 American Soldiers who served in the 1991 war. These Veterans have symptoms that include persistent headaches, memory and cognitive problems, widespread pain, and fatigue. The illness is believed to have been caused by exposure of the Soldiers to toxins such as pesticides, anti-nerve gas pills, and nerve gas. Unfortunately, the disease persists in the Veterans decades after exposure to the toxins, with no diminution of the symptoms. There is urgency in solving the mystery of how exposure to the toxins could cause a long-lasting illness so that future episodes of this kind can be prevented. There is even greater urgency in designing effective therapeutic regimens to treat the Veterans who are currently suffering from GWI, as they have been suffering for many years and their need is immediate. Inside the cells of the nervous system are cells called neurons that extend long thin processes called axons, many of which bundle together to form nerves. Axons are filled with architectural fibers called microtubules that serve as railroads along which structures inside the axon are moved in both directions. If anything detrimental happens to microtubules, the axon degenerates. Microtubules are known to gradually disintegrate in the brains of patients with Alzheimer s disease and also in the brains of patients with a one-time blow to the head resulting in traumatic brain injury. Hence, microtubules are extremely important for axons but are also extremely vulnerable to disease and injury. A small number of published studies indicate that the chemical toxins believed to cause GWI are detrimental to microtubules. If microtubule abnormalities are indeed a major cause of GWI, microtubule-based treatments that are already being developed for other diseases and injuries of the nervous system could be quite beneficial for treating patients with GWI. The purpose of the proposed research is to develop microtubule-based strategies for treating Veterans suffering from GWI, with emphasis on available drugs that can be readily translated into the clinic once shown to be helpful in these human cell studies. A key element of the study plan is to develop immortalized cultures of cells from the blood of Veterans who are suffering from GWI. A simple blood sample is taken from the Soldier, and then transduced in a special way, using reliable established methods, to make the cells pluripotent -- this means that the cells become very much like stem cells and can be turned into neurons, glial cells, immune cells, or almost any other cell of the body. The investigators will develop these cell lines from Veterans of the Gulf War who got sick and also from Veterans who did not get sick, so the two can be compared. Any other scientist studying GWI is welcome to use the cell lines for their own studies, which will maximize the effort of the biomedical community to rush medicines and treatment regimens to the Veterans who are suffering. For the 2-year proposed study, the first several months will be devoted to establishing these cell lines and the rest of the time will be devoted to conducting the microtubule studies. Given that microtubule-active drugs are already used in the clinic to treat cancer and given that clinical trials are underway to test their use for Alzheimer s disease, such drugs could be made available very rapidly in treatment trials to the Veterans suffering with GWI. The project brings together Dr. Peter Baas, an expert on microtubules who has studied them in the context of other neurodegenerative conditions, and Dr. Kimberly Sullivan, the leader of a large multisite consortium study (funded by the Department of Defense) on GWI from which the study participants will be recruited for this study. The consortium has many experts who can provide advice as the studies unfold. In addition, the team includes Dr. Liang Qiang, an expert o
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510433
Entities
People
- Peter W Baas
Organizations
- Drexel University
- United States Army