Researchers funded in part by MDA say a gene-based therapy designed to treat myasthenia gravis (MG) has shown promise in mice with an MG-like disease.
The research team was led by Dan Drachman, a longtime MDA research grantee at Johns Hopkins University in Baltimore, who also co-directs the MDA neuromuscular disease clinic at that institution. Drachman, a professor of neurology, has a special interest in MG, which is an autoimmune neuromuscular disease.
In autoimmune disorders, the body's immune system mistakenly attacks its own tissues. (Its usual role is to fight infection.)
Most people with MG produce antibodies (immune system proteins) against a part of the muscle fiber known as the acetylcholine receptor. Normally, signals pass from nerve fibers to muscle fibers through these receptors. In MG, however, this pathway is disrupted, leading to fluctuating weakness that can be debilitating and even life-threatening if the respiratory muscles become involved.
The goal of Drachman and colleagues, who published their results in the Oct. 15, 2012, issue of the Journal of Neuroimmunology, has been to disrupt the specific renegade immune response to the acetylcholine receptors while leaving the rest of the immune system intact.
The researchers created what they describe as "guided missiles" aimed only at the renegade immune system cells. They equipped the guided missiles with a "warhead" designed to kill the cells at which it was aimed.
First, they removed antigen-presenting cells (cells that "present" proteins to the immune system) from mice; they then genetically modified these cells so that they presented acetylcholine receptor proteins and injected them into mice with an MG-like disorder. That action, by itself, would be expected to worsen the autoimmune, MG-like disease.
But the researchers added a secret weapon — what they called a "warhead"— to the antigen-presenting cells, again using genetic engineering. The warhead, known as Fas ligand, interacts specifically with activated immune system cells (activated T cells in this situation) and kills them. The strategy therefore targets the very cells that are activated against acetylcholine receptor proteins.
The treatment dramatically reduced the immune response to the acetylcholine receptors in the mice, without interfering with the rest of the immune system. However, the researchers say, the study was not long enough to determine whether the mice were permanently cured of their disease.
"Theoretically, a similar approach to treatment could be translated to patients with myasthenia gravis," says an Oct. 1 press release from Johns Hopkins Medicine, "but so far it has not yet been tested in humans, and it is not yet known whether repeated courses of the therapy might be needed."
Current treatments for MG include:
None of these treatments is as specific as the one Drachman and colleagues hope to develop.
Various other experimental therapies also are in development for MG.
To learn more about autoimmune disease in general and MG in particular, see: