Possible eligibility criteria for Pompe disease (PD) patients that could be candidates for enzyme replacement therapy (ERT) with adeno-associated virus (AAV) gene therapy, according to a study recently published in JIMD Reports.

“Determining the best parameters to measure efficacy of intervention and overcoming immune phenomena are problems that are broadly relevant as AAV vector-mediated gene therapy will likely be developed as a new therapeutic modality for multiple inborn errors of metabolism,” the authors wrote.

Read more about PD therapies

Continue Reading

The study focused on evaluating the safety and efficacy of ERT using a specific AAV subtype known as AAV2/8-LSPhGAA. The investigators included 19 adults with late-onset PD and conducted the research at Duke University.

Inclusion criteria included a confirmed diagnosis of PD, being 18 years of age and above, and having stable ERT treatment for a minimum of 104 weeks. Exclusion criteria considered factors such as severe respiratory impairment, the presence of antiAAV8 antibodies, and certain medical conditions.

The study assessed various genetic, biochemical, and clinical parameters to determine eligibility and monitor treatment response to ERT with AAV8.

The results indicated that screening data from these individuals with late-onset PD reflect the heterogeneous nature of the disease. Participants exhibited varying levels of disease severity and clinical parameters, underscoring the importance of a thorough baseline assessment for eligibility determination and treatment response evaluation. This assessment included functional physical therapy assessments like the 6-minute walk test, disease biomarkers, and positional spirometry.

The study further revealed that a significant proportion of participants had neutralizing antiAAV8 antibodies with titers greater than 1:5. This scenario implies a considerable challenge for potential gene therapy candidates.

The study “raises the need to consider future studies with immunosuppressive therapy, or other strategies, to deplete antiAAV antibodies in individuals with Pompe disease to make AAV vector-mediated gene therapy available to them,” the researchers concluded.


Hannah W, Case L, Smith E, et al. Screening data from 19 patients with late-onset Pompe disease for a phase I clinical trial of AAV8 vector-mediated gene therapy. JIMD Rep. Published online August 17, 2023. doi:10.1002/jmd2.12391