rAAV1-CMV-hGAA is a type of gene therapy for Pompe disease that is being developed by researchers at the University of Florida.

How rAAV1-CMV-hGAA works

Pompe disease is a caused by a genetic mutation in the GAA gene that leads to abnormally low levels of an enzyme called acid alpha-glucosidase. This enzyme is responsible for breaking down a complex sugar molecule called glycogen into glucose, which the cells can use to produce energy. When there is not enough acid alpha-glucosidase enzyme, glycogen accumulates inside cells. This is toxic to many tissues in the body, especially to muscles, leading to muscle weakness and dysfunction.

rAAV1-CMV-hGAA consists of a virus, which has been rendered harmless (known as recombinant adeno-associated virus type 1 or rAAV1) that carries a healthy copy of the human GAA gene (hGAA). Injecting rAAV1-CMV-hGAA into the body allows the virus to transfer the normal GAA gene into the patient’s cells, increasing amounts of the acid alpha-glucosidase enzyme being produced and eliminating excess glycogen in the cells.

This gene therapy may be able to tackle the root cause of Pompe disease more effectively than enzyme replacement therapy (ERT), the currently accepted standard of treatment for the condition.

rAAV1-CMV-hGAA in clinical trials

Severe breathing problems frequently affect children with Pompe disease and may necessitate the use of special machines called ventilators that help them breathe. rAAV1-CMV-hGAA improved breathing abilities in a small Phase 1/2 clinical trial (NCT00976352) involving five children who were all dependent on ventilators and who were not responding to ERT.

During the trial, patients received one session in which three injections of rAAV1-CMV-hGAA were given directly into different areas of their diaphragm (the main muscle that controls breathing). They were then followed up to determine the treatment’s effectiveness and safety. The study began in 2010 and was completed in 2015.

Results showed that patients experienced significantly improved breathing abilities that continued to get better even at one year after receiving the injections. Some patients were able to breathe on their own for a few minutes to an hour or more without using the ventilator. Another article published in 2017 reported that rAAV1-CMV-hGAA was safe, with no patients experiencing side effects related to the treatment.

Further details 

The research team has since been working on using a different virus that may be more efficient in transporting the healthy gene into patient cells. The updated gene therapy, rAAV9-DES-hGAA, is being tested in a Phase 1/2 clinical trial (NCT02240407).


Pompe Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Pompe Disease News, or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Pompe disease.