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.
The Journal of Clinical Investigation study was funded by the NIH and the Muscular Dystrophy Association. Mei is a Georgia Research Alliance Eminent Scholar in Neuroscience.
Toni Baker | EurekAlert!
On track to heal leukaemia
18.01.2017 | Universitätsspital Bern
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Power and Electrical Engineering
18.01.2017 | Materials Sciences
18.01.2017 | Life Sciences