Although there currently is no cure for the disorder, Pompe disease treatments can help to ease its symptoms. The symptoms of Pompe disease are caused by missing or insufficient amounts of an enzyme called acid alpha-glucosidase (GAA). This enzyme is needed to break down glycogen, a complex sugar molecule, into glucose.
Full Answer
What is enzyme replacement therapy for Pompe disease?
Enzyme replacement therapy (ERT) is an effective treatment for Pompe disease. It involves injecting alpha-glucosidase directly into the bloodstream. ERT helps the body to break down glycogen and prevents its toxic buildup.
Can AD-AAV-HGAA Gene Therapy treat Pompe disease?
These Ad-AAV-hGAA vectors produced detectable GAA protein after liver-directed targeting and were able to clear glycogen in the skeletal muscle of GAA KO mice [ 32, 33 ]. Since then, the focus has primarily been on using AAV gene therapy for treating Pompe disease.
Is there a pipeline for the development of antisense oligonucleotides in Pompe disease?
From Cryptic Toward Canonical Pre-mRNA Splicing in Pompe Disease: A Pipeline for the Development of Antisense Oligonucleotides. Mol. Ther.
Is there any research being done on Pompe disease?
Research related to Pompe disease is conducted in one of the laboratories of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health. Much of Pompe-related research focuses on finding better ways to prevent, treat, and ultimately cure this disorder.
What role does an enzyme play in Pompe disease?
Pompe disease happens because of a mutation (a change) in a gene that helps make an enzyme called alpha-glucosidase. This enzyme breaks down a type of glucose called glycogen . When the enzyme is not made properly, glycogen builds up in the body's cells.
What is enzyme replacement therapy for Pompe?
Enzyme replacement therapy (ERT) is the only effective form of treatment for Pompe disease. It consists of injecting alpha-glucosidase directly into your bloodstream. As a result, your body breaks down glycogen stores and prevents toxic buildups in your cells.
What is an effective way to treat Pompe's disease?
Enzyme replacement therapy (ERT) is an approved treatment for all patients with Pompe disease. It involves the intravenous administration of recombinant human acid alpha-glucosidase (rhGAA).
What current research is being done to develop a cure for Pompe disease?
Researchers at Duke Health are developing a gene therapy approach for Pompe disease. This treatment uses a virus to deliver a healthy copy of the gene that is mutated in Pompe, the GAA gene, into the patients' liver cells.
Why does enzyme replacement therapy work?
How Does Enzyme Replacement Therapy Work? ERT balances low levels of glucocerebrosidase (GCase) enzyme with a modified version of the enzyme. This enzyme breaks down glucocerebroside, the fatty chemical that accumulates in the body of patients with Gaucher disease.
How is enzyme replacement therapy done?
Enzyme Replacement Therapy: The Basics The most common method of ERT is through IV infusions, in which the replacement enzyme is administered directly into the bloodstream through a controlled drip of fluids.
What is GAA biology?
Normal Function. Collapse Section. The GAA gene provides instructions for producing an enzyme called acid alpha-glucosidase (also known as acid maltase). This enzyme is active in lysosomes, which are structures that serve as recycling centers within cells.
Can you survive Pompe disease?
Survival from diagnosis The estimated 5-year survival after diagnosis was 95%. At 10, 20 and 30 years this was 83, 65 and 40%, respectively (Figure 1). Survival estimates of 268 untreated adults with Pompe disease from diagnosis until end of study, start of ERT or death. Twenty-three patients died during follow-up.
How are lysosomes affected by Pompe disease?
Pompe disease is a lysosomal storage disorder in which acid alpha-glucosidase (GAA) is deficient or absent. Deficiency of this lysosomal enzyme results in progressive expansion of glycogen-filled lysosomes in multiple tissues, with cardiac and skeletal muscle being the most severely affected.
What happens in Pompe disease?
Pompe disease happens when your body can't make a protein that breaks down a complex sugar, called glycogen, for energy. Too much sugar builds up and damages your muscles and organs. Pompe disease causes muscle weakness and trouble breathing.
Who discovered Pompe disease?
In 1932, Johannes Cassianus Pompe, a Dutch pathologist, described the disease in a 7-month-old infant who died of idiopathic hypertrophy of the heart; in addition to the cardiac problems, the infant had generalized muscle weakness.
What does acid alpha-glucosidase do?
Acid alpha-glucosidase is the enzyme responsible for degradation of glycogen polymers to glucose in the acidic milieu of the lysosomes. Cardiac and skeletal muscles are the two major tissues affected by the accumulation of glycogen within the lysosomes.
Treatment
Pompe disease is a multisystem disorder caused by mutations in the GAA gene that codes for the enzyme, acid alpha-glucosidase (GAA), 1 which breaks down glycogen into glucose to be used as an energy source for the cells. Defects in the enzyme prevent glycogen breakdown, causing a toxic accumulation of glycogen inside the cells.
Enzyme Replacement Therapy
Currently, the only available, specific, and effective treatment for Pompe disease is enzyme replacement therapy (ERT), 3 which was first approved in 2006 for use in patients with infantile-onset Pompe disease (IOPD).
Limitations of ERT
ERT has improved cardiac function and extended survival times in patients with IOPD. However, patients are not fully cured and residual symptoms remain. Respiratory and swallowing functions are only stabilized. About 30% of patients who received ERT still require assisted ventilation. 5
Future ERT Studies
To overcome the limitations of rhGAA therapy, modified rhGAA (avalglucosidase alfa, Neo-GAA) with a higher affinity for M6P receptors is being investigated in a phase 3 clinical study (NCT02782741). 6
Novel Mouse Model of Pompe Shows Potential of New Gene Therapy
In Pompe, mutations in the GAA gene, which encodes instructions to make the GAA enzyme, either prevent its production or result in the abnormal production of a non-functional enzyme.
Enzyme Replacement Therapy Loses Effectiveness in Pompe Patients with Long-term Use, Study Suggests
Other superior effects of gene therapy compared with ERT included restoring autophagy and mitochondrial function. Of note, the mitochondria are the energy-producing organelles of the cells.