For rare diseases in which no current treatment options are available, such as GM1 gangliosidosis, there is an urgent need to find therapeutics and improve patient outcomes. Gene therapy company Lysogene is trying to fill this unmet need for patients with GM1 gangliosidosis using its investigational gene therapy candidate LYS-GM101. According to a news release from Lysogene, the first U.S. patient has been dosed in a Phase 1/2 clinical trial evaluating the therapy’s safety and efficacy. While the trial hopes to enroll 16 patients with early or late infantile GM1 gangliosidosis, this US patient is only the 2nd dosed in the entire study.

LYS-GM101

So what exactly is LYS-GM101? According to Lysogene, this therapy is:

designed to restore the production of a key enzyme that is missing in patients suffering from GM1 gangliosidosis, a rare inherited lysosomal storage disorder for which there are no approved treatments. The therapy has the potential to reduce or prevent neuronal damage and thereby improve quality of life and extend the lifespan of young patients with the condition.

During the trial, patients will receive the treatment intracisternally. LYS-GM101 uses an adeno-associated viral (AAV) vector to deliver a functional GLB1 gene to patients. Thus far, LYS-GM101 has received Rare Pediatric Disease and Orphan Drug designations in the United States, as well as Orphan Drug designation in Europe. Outside of this clinical trial, Lysogene is also helping to run a natural history study to develop a deeper understanding of GM1 gangliosidosis.

GM1 Gangliosidosis

GLB1 gene mutations cause GM1 gangliosidosis, a rare and progressive lysosomal storage disorder. Normally, GLB1 works to produce beta-galactosidase, an enzyme which helps break down substances like GM1 ganglioside. However, gene mutations, inherited in an autosomal recessive pattern, prevent the body from breaking down GM1 ganglioside. As this accumulates, it becomes neurotoxic and causes neuron death in the brain and spinal cord. In many cases, GM1 gangliosidosis is considered either:

• Infantile (Type I): This form is considered the most severe form of GM1 gangliosidosis and is often fatal by early childhood. Symptoms typically appear around 6 months old and include:
  • Developmental regression
  • Muscle weakness
  • Seizures
  • Skeletal abnormalities
  • Exaggerated startle response
  • Vision loss and corneal clouding
  • Enlarged spleen, liver, and gums
  • Intellectual disability
  • Cardiomyopathy
  • Cherry-red spots in the eyes
• Late infantile/juvenile (Type II): In this form, symptoms appear between ages 18 months to 5 years. Unlike infantile GM1 gangliosidosis, the overall life span lasts slightly longer into mid-childhood or early adulthood. Symptoms include most of those associated with the infantile form, without liver and spleen enlargement or cherry-red spots.
• Adult/chronic (Type III): Adult GM1 gangliosidosis is considered the mildest form. Typically, symptoms appear in teenage years and include:
  • Spinal abnormalities
  • Dystonia

Learn more about GM1 gangliosidosis.