MDA awarded a research grant totaling $186,372 over a period of two years to Eric Sjoberg, principal scientist at Amicus Therapeutics in La Jolla, Calif. The funds will help support Sjoberg's research into immune system response associated with enzyme replacement therapy (ERT), the only approved treatment for Pompe disease (acid maltase deficiency or AMD).

In ERT, the acid maltase enzyme (GAA) is administered via intravenous infusion. The therapy has made a great difference in the lives of many people with Pompe disease, but challenges remain.

The majority of Pompe patients on ERT develop antibodies against GAA that can severely limit their ability to tolerate the drug, and also limit the ability of the drug to work, Sjoberg said. Evidence suggests that a specific genetic factor called "HLA type" in the patient population may be behind the unwanted immune response.

It's known that malformed or otherwise abnormal proteins are more likely to provoke an immune response than those with proper conformation (folding). GAA rapidly denatures in the neutral pH environment of plasma, the site in which the ERT is administered. This could be a possible cause of the ERT-mediated immune system response.

We have developed a specific pharmacological chaperone (a small molecule that selectively binds and stabilizes the target enzyme) for GAA, Sjoberg said. The molecule, AT2220, stabilizes the enzyme at neutral pH, Sjoberg said, noting that stabilizing GAA in plasma may mitigate the immune response associated with ERT treatment.

Sjoberg and colleagues plan to test ERT with and without AT2220 to determine whether a link exists between HLA types and ERT-mediated immune response. The investigators also will determine whether AT2220 can dampen ERT-related immune response.

Funding for this MDA grant began February 1, 2012.