Audentes is developing AT132 for the treatment of X-Linked Myotubular Myopathy (XLMTM).
XLMTM is a rare, inherited disorder characterized by severe muscle weakness and respiratory impairment. It is caused by mutations in the MTM1 gene, which encodes an enzyme called myotubularin. Myotubularin is thought to be involved in the development and maintenance of muscle cells. XLMTM affects approximately 1 in 50,000 newborn males worldwide.
What is X-Linked Myotubular Myopathy (XLMTM)?
X-Linked Myotubular Myopathy (XLMTM) is an ultra-rare, congenital muscle disease that primarily affects boys. XLMTM is caused by a mutation in the MTM1 gene, resulting in a lack of or dysfunction of the myotubularin protein.1,2 Most patients with XLMTM suffer significant morbidity.2 As they grow, children require supportive care that may include ventilator assistance, motorized wheelchairs and feeding tubes. While the initial diagnosis may feel scary, learning about the disease is important, and can empower you to start taking greater control of your child’s condition.
What are the symptoms of XLMTM?
- profound muscle weakness
- often require ventilatory support
- unable to swallow requiring frequent suctioning and nutritional support via gastrostomy tube
- require ventilatory and nutritional support
- frequent suctioning
- muscle function will diminish as they grow taller
For more information about the symptoms of XLMTM, please visit our X-Linked Myotubular Myopathy symptoms page.
How do we confirm a diagnosis of XLMTM?
Currently, initial diagnosis is based on clinical observations, and may be confirmed by a muscle biopsy and/or genetic testing. If you have a family history of XLMTM, genetic testing can confirm a diagnosis.
How did my child get XLMTM?
XLMTM is an inherited, X-linked disease, which means that it is transmitted through the X chromosome. Chromosomes are the structures that hold all of our DNA. Females have two X chromosomes (one inherited from their mother and one inherited from their father). Males have one X chromosome (inherited from their mother) and one Y chromosome (inherited from their father).
XLMTM is predominantly seen in males. This is because females have two copies of the X chromosome that holds the XLMTM1 gene. The effects of a mutated gene on one X chromosome can usually be overcome by the normal (“wild-type”) MTM1 gene on their other X chromosome. Since males have only one X chromosome, the effect of a mutated MTM1 gene cannot be overcome by a second, wild-type copy, so the symptoms of XLMTM will be present.
Genetic counseling is recommended to evaluate family history and future risk.
How is XLMTM treated?
XLMTM is a genetic, lifelong disease. Children may receive supportive care ranging from continuous ventilator support to respiratory support only at night. Most people affected by XLMTM require a gastrostomy tube for nutritional support. There is currently no disease-modifying therapy available for XLMTM. Once diagnosed, you and your team of healthcare professionals can work together to manage the disease.
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 XLMTM 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.