Gene Therapy Effective For Pompe Disease In Mice Prepared For Human Trials: Study

Duke Health researchers have developed a gene therapy that could enhance or even replace the only FDA-approved treatment currently available to patients with a rare, life-threatening condition that cripples the muscles. The condition known as Pompe disease is inheritable and affects around 1 in every 20,000 babies and can also affect adults.

The gene therapy used in mice utilizes a modified virus to send a gene, which produces GAA to the liver - an enzyme people with Pompe disease do not have. The study authors have received approval from the FDA to conduct a Phase 1 clinical trial in humans and are now working to secure funding for the research.

People with the condition do not have the GAA enzyme, which invariably means their bodies will not be able to breakdown sugar, resulting in the buildup of glycogen in the muscles. The abnormal buildup causes improper muscle development in babies and can lead also to respiratory problems, heart failure and even death, if left undiagnosed and untreated.

"The outlook for Pompe disease is much improved since enzyme replacement has become available - it can reverse involvement of the heart and prolong survival," professor of pediatrics, a medical genetics specialist at Duke and a senior author, Dwight Koeberl, M.D., Ph.D. said.

He added that not everyone responds to this treatment as most patients produce some antibodies that can interfere with treatment. While so many infants still die from the condition, others have to add immune suppression to their treatment, which can also give rise to other complications. The researchers believe that gene therapy could have a great impact on people with Pompe diseases, according to Eurekalert.

They found that a single dose of gene therapy was as effective as enzyme replacement therapy (ERT) in clearing the buildup of glycogen from the muscles in mice, with the treatment inducing the continuous production of GAA in the liver, without additional treatment. Enzyme therapy requires infusions up to twice a month to reduce the level of glycogen in the muscles.

The gene therapy does not trigger immune response like the enzyme therapy. Immune response is a reaction capable of reducing the percentage of successful treatment in up to half of babies with Pompe disease. The gene therapy does not only avoid this reaction, it appeared to reverse it completely in mice that had already developed antibodies in response to enzyme replacement.

Koeberl explains that the gene therapy utilizes an inactivated form of adeno-associated virus (AAV), which doesn't cause illness and has been used as a delivery system for hemophilia B and muscular dystrophy treatments, among others, according to Science Daily.

The emerging gene therapy is the latest achievement for the team of researchers at Duke that has been working for three decades to investigate the causes and potential treatments for glycogen-storage diseases with much focus on Pompe disease. The researchers had also helped develop a blood test to diagnose Pompe and a biomarker to check severity of the disease and monitor patients' response to treatment.

The researchers are now working towards developing a molecule or oral medication that would inhibit the buildup of glycogen in the muscles. The researchers published their findings online in the journal Molecular Therapy - Methods & Clinical Development.