In recent years, there have been huge progressions in the field of gene therapy. At its core, gene therapy addresses genetic disorders by using genes to directly treat or prevent disease progression. This past month, biotechnology company Amicus Therapeutics (“Amicus”) announced positive data from its gene therapy program AT-GTX-501. Results on the gene therapy, designed for patients with CLN6 Batten disease, were presented at the Joint 16th International Child Neurology Congress and 49th Annual Child Neurology Society Meeting. Check out the Amicus website for the full presentation.
To begin, it is first necessary to understand what gene therapy actually is. According to MedLine Plus, gene therapy:
is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery.
There are multiple approaches to gene therapy, which include:
- Replacing a mutated gene that causes disease with a healthy copy of the gene.
- Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
- Introducing a new gene into the body to help fight a disease.
In this case, a single administration of AT-GTX-501, delivered intrathecally (through the spine), delivers a functional CLN6 gene to patients. Through this, researchers hope to prevent neuronal death and damage, improving patient outcomes. Currently, an ongoing Phase 1/2 clinical trial is determining the safety, efficacy, and tolerability of AT-GTX-501 for pediatric patients. So far, data is available for 13 patients with CLN6 Batten disease. Generally, AT-GTX-501 was well-tolerated, with few side effects. The gene therapy candidate also inhibited disease progression and reduced the decline of motor skills.
AT-GTX-501 received Rare Pediatric Disease, Orphan Drug, PRIME, and Orphan Medicinal Product designations in the U.S. and European Union.
Also known as neuronal ceroid lipofuscinosis (NCL), Batten disease is an inherited lysosomal storage disorder that impacts the nervous system. In many cases, Batten disease is fatal by the mid-20s. The condition is characterized by the toxic accumulation of lipopigments (fat and protein) in body tissue. Ultimately, this causes brain, retina, and central nervous system (CNS) neuronal death. There are four main types of Batten disease, although there are 13 subsets in all, dependent on specific gene defects. These include:
- Infantile NCL, a fast-progressing form that usually occurs before age 2. Many with this form do not live past 8 years old.
- Late-infantile NCL, which begins between ages 2-4. Usually, patients live to ages 8-12.
- Juvenile NCL, which begins between ages 5-8. Many patients live through their teens or early 20s.
- Adult NCL, which begins before age 40.
Amicus’ particular gene therapy is designed for patients with variant late-infantile neuronal ceroid lipofuscinosis 6 (vLINCL6) disease, or CLN6 Batten disease. According to the National Institute of Neurological Disorders and Stroke (NINDS):
The gene CLN6, located on chromosome 15, directs the production of the protein CLN6, also called linclin, [which] is found in the membranes of the cell. Most children with CLN6 die during late childhood or in their early teenage years.
Symptoms of Batten disease vary. However, in patients with CLN6 Batten disease, they may include:
- Intellectual and developmental delays
- Changes in personality and behavior
- Dementia or confusion
- Vision loss
- Sleep interruptions
- Involuntary muscle contractions
- Loss of ability to walk, speak, or communicate
Learn more about Batten disease here.