continued from page 6 havior of proteins,” Dr. Taylor said. “And the change in the phase transition behavior changes the biology of the cell.” More broadly, he said, “These findings are part of an emerging theme that there is a whole spectrum of diseases that includes ALS, and some forms of dementia and myopathy, that are caused by disturbance in the behavior of these structures that perturbs cellular organization.” The findings offer a highly promising pathway to the first effective treatments for ALS/FTD, Dr. Taylor said. Current drugs, which are only minimally effective, seek to improve the function of already damaged neurons. However, the new findings suggest the possibility of treatments that would prevent neuronal damage by restoring the healthy balance of phase separation in the cells of people with ALS/FTD mutations. “We know that these material properties are under tight regulation, so perhaps we don’t have to target the disease-causing mutation itself,” Dr. Taylor said. “Perhaps we can restore balance by targeting any of a large number of regulatory molecules in the cell. There are already therapeutic approaches in laboratory testing that seek to do just that.” In further studies, Dr. Taylor and his colleagues will seek to understand the basic process of phase transition. They will also map the regulatory machinery for stress granules, to seek potential therapeutic targets. He also noted that the same basic pathology of phase transition may also underlie other neurodegenerative diseases, including Alzheimer’s disease, and he is aiding researchers in applying the same research approach as in ALS/FTD to Alzheimer’s. The paper’s joint first authors are Ian Mackenzie of Vancouver Coastal Health and the University of British Colombia; Alexandra Nicholson of Mayo Clinic Jacksonville; and Mohona Sarkar of St. Jude. Other St. Jude co-authors were Jamshid Temirov, Hong Joo Kim and Tanja Mittag. The research was funded in part by Mayo Clinic for Individualized Medicine; the Arizona Alzheimer’s Consortium; CREATE, the Canadian Institutes for Health Research; the National Institutes of Health and ALSAC, the fundraising and awareness organization of St. Jude.
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Father, Son Double-Team Autoimmune Disorders at UTHSC By MADELINE PATTERSON
A father and his son at the University of Tennessee Health Science Center are gaining attention for their contributions concerning autoimmune disorders. Arnold E. Postlethwaite, MD, AB, is the Goodman Chair of Excellence Professor of Medicine and director of the Division of Connective Tissue Diseases at UTHSC. He has been associated with Dr. Arnold Postlethwaite, left, and his son, Dr. Bradley Postlethwaite. the school since 1973 and with more than 150 publications on autoimmune disorders. tered peptide ligand, APL) can “turn off” And now the Postlethwaite impact is the progression of arthritis in the animal growing, as Bradley Postlethwaite, MD, model of RA. Dr. Arnold Postlethwaite Arnold’s son, also enters the field of rheuconducted a phase 1 study funded by the matology at University Clinical Health, VA in which patients took a daily solution one of the faculty practices affiliated with of Type II collagen APL before breakfast UTHSC. While the elder Postlethwaite for four months. did indeed teach his son, he says he did The hypothesis was the APL solution not encourage him to enter the field of could halt the immune reaction to Type II medicine. Collagen, with the eventual goal of helpDr. Bradley Postlethwaite “loves to ing RA patients slow the progression of interact with people, and in rheumatology the disease. The data are still being anayou take care of patients all their life belyzed. cause most of the diseases we treat never In addition to the VA study, Dr. Arget cured,” Dr. Arnold Postlethwaite said nold Postlethwaite is studying the relationof his son’s choice to enter his same field ship between UVB light and arthritis. The of practice and research. Dead Sea beaches in Israel have been a The Postlethwaite duo is collaborathaven for RA patients who report feeling on autoimmune research, specifically ing reduced symptoms for days after time for patients with scleroderma. spent in the sun. Researchers have estabIt is estimated that 50 million Amerilished the benefits of vitamin D for RA cans suffer from some type of autoimmune patients, but the “beach effect” is actually disease, including lupus, Crohn’s disease, UVB light providing temporary relief. scleroderma, rheumatoid arthritis and ce“UVB is something different – it liac disease, to name a few. Autoimmune produces a potent and fast suppression of disease is also the top cause of morbidity the immune system,” Dr. Arnold Postlefor women in the United States. thwaite says, but he cautions the treatment UTHSC is at the forefront of rheumaposes a cancer risk. If researchers can bettology research, and particularly rheumater understand what the UV light does to toid arthritis (RA) research. RA is primarily the immune system, then a therapy could the inflammation of joints that occurs when be developed without causing melanoma. the immune system attacks the body’s own Scleroderma occurs when there is an tissues. In the 1970s, Dr. Andrew H. Kang overproduction of type 1 collagen leadat UTHSC and the Memphis VA Mediing to hardening or “sclerosis” of the cal Center discovered and developed the tissue and organs in the body. The skin rodent model of type II collagen-induced and internal organs, such as the heart, GI arthritis, which is used worldwide as a tract and lungs, are susceptible to fibrosis, model for RA. More than 25,000 articles which impairs the function of the affected have been published on this model and the organ. There is no overall scleroderma topic, and UTHSC has continued to retreatment, but researchers are studying ceive grants from federal and private founoral tolerance to type 1 collagen from cow dations for its pioneering work. skin, which is like human type 1 collagen The elder Dr. Postlethwaite has spent as a therapy. much of his research career studying colA new test of genetic variants called lagen, as it plays a crucial role in undersingle nucleotide polymorphisms (SNPs) is standing scleroderma or systemic sclerosis, a major breakthrough to determine how and rheumatoid arthritis, his two areas of researchers study oral collagen treatment focus under the umbrella of autoimmune in clinical trials. Drs. Arnold Postlethwaite diseases. and Weikuan Gu discovered a mutation Today, Dr. Arnold Postlethwaite that indicates a patient can’t be toleratized and other physicians at UT are studying to collagen. how changing amino acids in peptides (alThe marker is a sign that the patient
will be resistant to oral collagen therapy, therefore researchers can more selectively identify systemic sclerosis patients for research studies. This SNPs study has not been published yet, but it’s in process with arGentis Pharmaceuticals. The cost associated with autoimmune disease in the United States is around $100 billion annually, and to put that in perspective, it’s estimated that the direct medical cost of cancer is $87 billion. While research for new therapies has progressed since the breakthrough rodent model at UTHSC in the ‘70s, there is potential for growth in understanding the immune system of the GI tract, where about 70 percent of the immune system lives.
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