Posts tagged myasthenia gravis
Articles and news from the latest research reports.
New cause found for muscle-weakening disease myasthenia gravis
An antibody to a protein critical to enabling the brain to talk to muscles has been identified as a cause of myasthenia gravis, researchers report.
The finding that an antibody to LRP4 is a cause of the most common disease affecting brain-muscle interaction helps explain why as many as 10 percent of patients have classic symptoms, like drooping eyelids and generalized muscle weakness, yet their blood provides no clue of the cause, said Dr. Lin Mei, Director of the Institute of Molecular Medicine and Genetics at the Medical College of Georgia at Georgia Regents University.
"You end up with patients who have no real diagnosis," Mei said.
The finding also shows that LRP4 is important, not only to the formation of the neuromuscular junction – where the brain and muscle talk – but also maintaining this important connection, said Mei, corresponding author of the paper in The Journal of Clinical Investigation.
Mei and his colleagues first reported antibodies to LRP4 in the blood of myasthenia gravis patients in the Archives of Neurology in 2012. For the new study, they went back to animals to determine whether the antibodies were harmless or actually caused the disease. When they gave healthy mice LRP4 antibodies, they experienced classic symptoms of the disease along with clear evidence of degradation of the neuromuscular junction.
LRP4 antibodies are the third cause identified for the autoimmune disease, which affects about 20 out of 100,000 people, primarily women under 40 and men over age 60, according to the National Institutes of Health and Myasthenia Gravis Foundation of America, Inc.
An antibody to the acetylcholine receptor is causative in about 80 percent of patients, said Dr. Michael H. Rivner, MCG neurologist and Director of the Electrodiagnostic Medicine Laboratory, who follows about 250 patients with myasthenia gravis. Acetylcholine is a chemical released by neurons which act on receptors on the muscle to activate the muscle. More recently, it was found that maybe 10 percent of patients have an antibody to MuSK, an enzyme that supports the clustering of these receptors on the surface of muscle cells.
"That leaves us with only about 10 percent of patients who are double negative, which means patients lack antibodies to acetylcholine receptors and MuSK," said Rivner, a troubling scenario for physicians and patients alike. "This is pretty exciting because it is a new form of the disease," Rivner said of the LRP4 finding.
Currently, physicians like Rivner tell patients who lack antibody evidence that clinically they appear to have the disease. Identifying specific causes enables a more complete diagnosis for more patients in the short term and hopefully will lead to development of more targeted therapies with fewer side effects, Rivner said.
To learn more about the role of the LRP4 antibody, Mei now wants to know if there are defining characteristics of patients who have it, such as more severe disease or whether it’s found more commonly in a certain age or sex. He and Rivner have teamed up to develop a network of 17 centers, like GR Medical Center, where patients are treated to get these questions answered. They are currently pursuing federal funding for studies they hope will include examining blood, physical characteristics, therapies and more.
Regardless of the specific cause, disease symptoms tend to respond well to therapy, which typically includes chronic use of drugs that suppress the immune response, Rivner said. However, immunosuppressive drugs carry significant risk, including infection and cancer, he said.
Removal of the thymus, a sort of classroom where T cells, which direct the immune response, learn early in life what to attack and what to ignore, is another common therapy for myasthenia gravis. While the gland usually atrophies in adults, patients with myasthenia gravis tend to have enlarged glands. Rivner is part of an NIH-funded study to determine whether gland removal really benefits patients. Other therapies include a plasma exchange for acutely ill patients.
Study finds association between rare neuromuscular disorder and loss of smell
Changes in the ability to smell and taste can be caused by a simple cold or upper respiratory tract infection, but they may also be among the first signs of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Now, new research from the Perelman School of Medicine at the University of Pennsylvania has revealed an association between an impaired sense of smell and myasthenia gravis (MG), a chronic autoimmune neuromuscular disease characterized by fluctuating fatigue and muscle weakness. The findings are published in the latest edition of PLOS ONE.
Most humans experience five types of tastes: sweet, salty, sour, bitter, and savory. The sense of taste is mediated by taste receptor cells which are bundled in our taste buds. “Sour” and “bitter” taste sensations alert the body to harmful foods that have spoiled or are toxic. But based on genetics, up to 25 percent of the population cannot detect certain bitter flavors (non-tasters), 25 percent can detect exceedingly small quantities (super-tasters), and the rest of us fall somewhere between these two extremes.
So what exactly does drinking a cup of bitter coffee have to do with chronic sinus infections, which account for approximately 18-22 million physician visits in the U.S. each year? Recent investigations have shown that these taste receptors (T2Rs) are also found in both upper and lower human respiratory tissue, likely signaling a connection between activation of bitter tastes and the need to launch an immune response in these areas when they are exposed to potentially harmful bacteria and viruses.
“With this information in mind, we wanted to better understand the exact role that bitter taste receptors play in the upper airway, especially between these super and non-tasters,” says Noam Cohen, MD, PhD, assistant professor of Otorhinolaryngology: Head and Neck Surgery, staff physician at the Philadelphia VAMC, and senior author of the new study.
(Source: medicalxpress.com)
Researchers Halt Autoimmune Disease Myasthenia Gravis in Mice
Working with mice, Johns Hopkins researchers say they have developed a gene-based therapy to stop the rodent equivalent of the autoimmune disease myasthenia gravis by specifically targeting the destructive immune response the disorder triggers in the body.
The technique, the result of more than 10 years of work, holds promise for a highly specific therapy for the progressively debilitating muscle-weakening human disorder, one that avoids the need for long-term, systemic immunosuppressant drugs that control the disease but may create unwanted side effects.
The research, if replicated in humans, could be a big leap in treating not only myasthenia gravis, but also other autoimmune disorders, the researchers say.
“To treat autoimmune diseases, we normally give drugs that suppress not only the specific antibodies and cells we want to inhibit, but that also broadly interfere with other functions of the immune system,” says Daniel B. Drachman, M.D., a professor of neurology and neuroscience at the Johns Hopkins University School of Medicine and leader of the study published this month in the Journal of Neuroimmunology. “Our goal was to suppress only the abnormal response, without damaging the remainder of the immune system, and that’s what we did in these mice.”