Socrates Tzartos, professor of biochemistry at the Hellenic Pasteur Institute in Athens, Greece, was awarded an MDA research grant totaling $345,033 over a period of three years to develop diagnostic tools for diagnosis of the low-density lipoprotein receptor-related protein 4 (LRP4) form of myasthenia gravis (MG).

MG is an autoimmune disease in which the body’s immune system targets proteins located at the neuromuscular junction, causing weakness. In most patients, the target is the acetylcholine receptor, and in others it is muscle-specific kinase. But 10 percent of MG patients do not have either of these forms, and are said to have seronegative MG (SN-MG). “SN-MG presents a serious gap in MG diagnosis and understanding,” says Tzartos.

Recently, antibodies against LRP4, another protein found at the neuromuscular junction, have been found in some SN-MG patients, and evidence suggests this may be another cause of disease. However, there is not yet a reliable, clinically practical test available for the routine diagnosis of LRP4-MG. Tzartos will be developing such a test by making the protein in animals, purifying it, and comparing a range of assays for their ability to detect the protein. He then plans to test a large number of SN-MG patients to determine the true prevalence of LRP4-MG among this group. Finally, he will explore the pathologic mechanisms at work in LRP4-MG in animal models.

“Since it is known that MG is heterogeneous [varied] in terms of pathophysiology [effects on the body], the outcome of this project is expected to have great impact for this group of MG patients, and provide new insights on the physiology of the neuromuscular junction,” Tzartos says.

Funding for this MDA grant began Feb. 1, 2013.