A fast acting 'vaccine' has been developed for myasthenia gravis

More than 60,000 Americans are dealing with myasthenia gravis (MG), an incurable autoimmune disease that causes weakness of the muscles. The primary treatments, which haven't changed since the 1950's are nonspecific immunosuppressants and inhibitors of the enzyme cholinesterase.

Recently , two researchers from the Perelman School of Medicine at the University of Pennsylvania have developed what might be called a fast-acting "vaccine" that
has been seen to reverse the course of the disease as it appears in rats. And there is hope that the same reversal process will work in humans.  The study was led by Jon Lindstrom, PhD, a Trustee Professor in the department of Neuroscience. It was published in the new issue of the Journal of Immunology, It was coauthored by top research investigator Jie Luo, PhD.

The cause of myasthenia gravis is an autoimmune response to the acetylcholine receptor (AChR), a protein of muscle groups that translates signals of the nervous system into contractions of the muscles. Autoantibodies target the part of these receptors found on the outer cell surface of muscle, leading to weakness.

Researchers can induce MG in rats by injecting the AChR protein, which produces an animal disease model called experimental autoimmune myasthenia gravis (EAMG). In this study, Lindstrom and Luo found that injecting rats with the part of the AChR found on the inside of the cell protects those animals from EAMG and reverses the course of the disease if administered after the EAMG has already been induced.

"We have an antigen-specific immunosuppressive therapy that works on the animal model and should work on human MG," says Lindstrom, adding that such therapies are "rarer than hens' teeth."

A vaccine dose of 1 mg per week for six weeks, the team found, was sufficient to block development of chronic EAMG in rats. But significantly, the vaccine also worked after induction of chronic EAMG, and could block re-induction of disease months later, as well. The vaccine appears to work by preventing synthesis of pathological antibodies to the extracellular surface of the AChR protein


Even though it's called a "vaccine," Lindstrom's therapeutic is not like the type of vaccine that's used for influenza or measles. In those cases, the concept is one which is to raise immunity to disease antigens that can then attack the pathogen should it infect the body in the future. However, with MG, the vaccine targets immune cells that recognize and target a self protein – the acetylcholine receptor, which helps transmit neural signals from cell to cell – and marks them for death.

"We are trying to modulate a deviant immune response," Lindstrom explains.

The trick here is that the vaccine is made not from the portion of the AChR protein that the immune system normally would see – that part that is exposed on the outer surface of cells. Instead, it is built using the protein's cytoplasmic, or inner, cell regions. This formulation induces a robust, antigen-specific suppression of the immune response without also inducing MG itself. This may involve inhibition of cells involved in making pathological antibodies and regulating that response, but the exact mechanisms have not yet been determined.

Lindstrom's lab first described the vaccine itself in a 2010 publication in the Annals of Neurology. But this earlier work didn't try to block or treat chronic disease, and injected the vaccine without the use of a chemical cocktail that amplifies the resulting immune response, called an adjuvant. The present study suggests that pairing the vaccine with an adjuvant is safe – that is, it doesn't cause MG – and effective.

Now, says Lindstrom, the goal is to test this approach in animals with EAMG and MG using other human adjuvants and then move to human clinical trials.