The trial (NCT04174105) will be conducted at clinical sites in the U.S., Germany, and the U.K. It aims to recruit up to eight participants, ages 18 to 80, who have received Lumizyme (alglucosidase alfa, marketed as Myozyme in Europe), an enzyme replacement therapy, for at least two years and as a stable dose for six months prior to enrollment. Both ambulatory and non-ambulatory patients may be eligible.
Recruitment is currently open in two U.S. locations. More information on trial sites and contacts is available here.
Pompe disease is caused by mutations in the GAA gene, which lead to a deficiency in the enzyme acid alpha-glucosidase (GAA). Reduced levels or lack of this enzyme results in the accumulation of glycogen — a type of sugar — in cells throughout the body.
AT845 was designed to promote long-term production of the GAA enzyme by delivering a functional version of the GAA gene directly to muscle cells. As such, AT845 differs from gene therapies that target the liver, which still require the transport of the GAA enzyme from the liver to muscles. In AT845, the gene is placed inside a modified, harmless adeno-associated virus (AAV8), which acts as a carrier inside the body.
Unlike enzyme replacement therapy — the current standard treatment for people with Pompe that requires frequent administrations — AT845 was designed to be given in a single dose.
In the trial, participants will receive one of two doses of AT845 delivered via intravenous infusion (directly into the bloodstream). The study’s goals are to determine the gene therapy’s safety at week 48 after treatment, as well as the levels and activity of the GAA enzyme in muscle biopsies at week eight.
Questions and requests for additional information may be emailed to [email protected]
In preclinical studies with GAA-deficient mice, AT845 led to significant increases in enzyme activity in heart and skeletal muscle (used for movement). Such benefits were associated with improved diaphragm contractile strength, lower cardiac glycogen and mass in the heart’s left ventricle, and better ejection fraction — an assessment of how much blood the left ventricle pumps out with each contraction.
Another study in a mouse model of Pompe showed that a single injection of AT845 and bi-monthly injections of a lab-made human GAA over three months led to improvements in diaphragm contractile strength and cardiac function.
Respiratory improvements were only seen with AT845, while glycogen accumulation was significantly increased in untreated and human GAA-treated animals, but not in mice receiving AT845.
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