A gene therapy for the treatment of GM1 gangliosidosis was granted Orphan Drug Designation in April. PBGM01 seeks to treat the most severe form of this condition – infantile. Read the full press release here.
GM1 gangliosidosis is a rare genetic disorder categorized by the degeneration of brain and spinal nerve cells. It is caused by a mutated GLB1 gene. This lysosomal storage disease is broken down into three subsets:
- Type I / Infantile: this is the most severe type of GM1 gangliosidosis. Symptom onset occurs before 6 months old. Prior to becoming symptomatic, infants usually show signs of normal development.
- Symptoms include exaggerated startle reactions, developmental regression, muscle weakness, organ enlargement and skeletal defects, vision loss, intellectual delays, seizures, enlarged gums, cardiomyopathy, and distinct facial features. An additional symptom is a cherry-red spot, which can be found through an eye examination.
- Most patients with Type I GM1 gangliosidosis do not live past childhood. There are no cures. However, patients can be supported via ventilators, feeding tubes, or other similar medical equipment.
- Type II: this is known as late infantile or juvenile GM1 gangliosidosis. Similar to those with Type I, people with Type II have normal development. However, symptom onset occurs around 18 months for late infantile to 5 years for juvenile GM1 gangliosidosis.
- Symptoms include developmental regression. However, unlike Type I, symptoms do not include organ enlargement, distinct features, or cherry-red spots.
- Patients may survive into mid-childhood or early adulthood.
- Type III: Adult or chronic GM1 gangliosidosis is the least severe form of the disorder. Symptom onset varies, but normally occurs in teenage years. Symptoms include spinal abnormalities and involuntary muscle rigidity.
PGBM01 is a gene therapy developed by Passage Bio, a genetic medicines company that develops therapies for rare central nervous system conditions. In April, the therapeutic solution was given the Orphan Drug Designation by the FDA.
According to Investopedia, Orphan Drug status:
gives companies researching cures for rare diseases a seven-year window of tax reductions and the exclusive right to develop a cure for a specific condition.
In this case, “rare diseases” mean conditions that affect under 200,000 people in the United States.
PBGM01 uses AAV-delivery, or adeno-associated-virus delivery. GeneTherapy.net describes AAVs as:
small viruses with a genome of single stranded DNA. These viruses can insert genetic material…with near 100% certainty.
Additionally, AAVs are not pathogenic. So the immune system won’t target or attack them. They’re actually relatively harmless! PBGM01 uses AAVs to deliver a working GLB1 gene to the brain and other tissues, which can reverse neuronal damage.