Audentes is developing AT982 for the treatment of Pompe disease.
Pompe disease is a rare, inherited disorder characterized by progressive muscle weakness and respiratory impairment. It is caused by mutations in a gene that encodes an enzyme called acid alpha-glucosidase (GAA), which is needed by the body to break down glycogen – a stored form of sugar used for energy. Pompe disease affects approximately 1 in every 40,000 births.
What is Pompe Disease?
Pompe disease is a rare, inherited disorder caused by mutations in the acid alpha glucosidase (GAA) gene.1 The GAA gene provides instructions to the body for producing the acid alpha-glucosidase enzyme (also known as acid maltase). This enzyme is active in lysosomes, which are structures that serve as recycling centers within cells. The enzyme normally breaks down glycogen into a simpler sugar called glucose, which is the main energy source for most cells. 2
Mutations in the GAA gene prevent acid alpha-glucosidase from breaking down glycogen effectively, which allows this sugar to build up to toxic levels in lysosomes.3 This buildup damages organs and tissues, particularly the muscles. This leads to the progressive signs and symptoms of Pompe disease.3
Pompe disease affects approximately 1 in 40,000 people worldwide. The disease can occur in males and females of all ethnicities and can be diagnosed from infancy to adulthood.2 It may be scary to find out that you or your loved one is living with Pompe disease. Learning about the disease is important, and it can empower you to take control.
How do you get Pompe disease?
Pompe disease is known as an autosomal recessive inherited disease. People have 23 chromosomes. If one particular gene on chromosome 17 is defective in an individual (the gene that encodes GAA), that person is said to be a “carrier” of Pompe disease.2
As an autosomal recessive disease, someone must carry two defective copies of the GAA gene in order to have Pompe disease. This typically means that both parents contributed a defective copy and are either “carriers” with one normal copy and one defective copy, or were affected by Pompe disease themselves and had two defective copies.
What are the symptoms of Pompe disease?
The signs and symptoms of Pompe disease vary depending on age and severity of the disease.
For more information about the symptoms of Pompe disease, please visit our Pompe disease symptoms page.
How do we confirm a diagnosis of Pompe disease?
Pompe disease can be challenging to identify because many of its symptoms are shared with other diseases. A patient may see several doctors to rule out other, more common disorders that share similar symptoms, such as multiple sclerosis or muscular dystrophy. Pompe disease can be diagnosed in one of three ways:
- Blood test that measures GAA enzyme activity. Low GAA activity is indicative of Pompe disease.
- Skin or muscle biopsy. This is considered the “gold standard” for diagnosing Pompe disease.
- Molecular or genetic testing. The identification of alleles (variant forms of the GAA gene) is useful for identification of carrier or affected status in other family members.4
How is Pompe disease treated?
Pompe disease is a rare, inherited, lifelong disease. Currently, enzyme replacement therapy (ERT) is available to treat Pompe disease. Patients receive ERT treatment in biweekly intravenous infusions. There are several other potential new therapies currently in various stages of clinical development.
What is gene therapy?
Gene therapy is a technique that uses genes to treat or prevent disease by inserting a properly functioning version of a defective gene into a patient’s cells. The inserted gene is able to produce functional protein with the therapeutic goal of improving the patient’s symptoms. The most common form of gene therapy involves the delivery of a functional gene through the use of a vector. Vectors are derived from viruses and are capable of entering cells in the body efficiently. One type of virus used for this purpose is called adeno-associated virus, or AAV. Audentes uses AAV technology for its Pompe disease program.
What is adeno-associated virus (AAV)?
AAV is a virus that is common in humans, but is not known to cause disease. AAV has been studied extensively and has been proven to be a leading candidate as a vector for human gene therapy. Encouraging safety and efficacy results have been published using AAV for multiple preclinical and clinical studies.
How does a clinical trial work?
Clinical trials evaluate potential treatments for a specific disease for safety and efficacy.
Clinical trials follow a highly defined process, known as a protocol, which is proposed by the company that is developing the treatment, is reviewed by regulatory agencies, and is then approved by the Investigational Review Board (IRB) of the institution or institutions conducting the study. The protocol will define the criteria of who can enroll in the study, the method of treatment, the tests used to monitor the safety of the treatment, and the long-term follow up needed to ensure the drug continues to provide benefit and is safe over time.
Consider speaking with your team of healthcare professionals about whether or not a clinical trial may be suitable for you and your family.
For more information visit: clinicaltrials.gov
Please visit our Patient Advocacy website here for additional information about our clinical programs and a list of patient resources that can help you and your loved one. Additionally, on our Patient Advocacy website you will find inspiring patients’ stories and a calendar of upcoming events that may be of interest to you.