A new study elucidating molecular structures contributing to enzyme uptake and immunoreactivity of enzyme replacement therapy in Pompe disease is now open. The ultimate aim of the investigators is to develop enzyme replacement therapies that are individually tailored for patients with the disease.

The study will consist of 2 parts. In the first, investigators will characterize the molecular structure of wild-type alpha-glucosidase (GAA) enzyme and mutated variants with and without high sustained antibody titers. The goal is to better understand how mutations impair enzyme uptake into cells via the M6P receptor.

To do so, they will identify antibody epitopes in the sera of patients with recombinant human GAA antibodies and determine and compare their binding affinities.

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In the second part, investigators will synthesize and chemically modify the epitope peptides of the enzyme to block antibodies directed against them to identify which ones are most important. They reason that applying high-affinity GAA epitope peptides that can bind neutralizing antibodies could potentially improve the safety and efficacy of enzyme replacement therapy, “thereby providing a new targeted and personalized immunotolerance approach.”

Read more about enzyme replacement therapy for Pompe disease

The observational, case-control study aims to recruit 50 patients with infantile-onset or late-onset Pompe disease and healthy volunteers with normal GAA enzyme activity.

The study will take place at the Centre for Analytical Biochemistry Rüsselsheim in Hessen, Germany, and is expected to be completed on October 7, 2024.

The primary outcome measures are the number and location of epitopes of wild-type, recombinant, and mutated GAA enzyme as well as epitope-specific affinities of antibodies. Secondary outcome measures are the number of Pompe disease patients with specific neutralizing antibody epitopes and the determination of antibody titers in patients.

Enzyme replacement therapy has been shown to be effective in the treatment of Pompe disease but the response to treatment varies greatly from patient to patient. 


ERT in Pompe disease: elucidation of molecular structures contributing to enzyme uptake and immunoreactivity. US National Library of Medicine. Last updated July 7, 2022. Accessed August 1, 2022.