In an exciting press release, gene therapy platform company Lysogene announced that it had received approval from the Medicines and Healthcare products Regulatory Agency (MHRA) and Research Ethics Committee. As a result of this approval, Lysogene is able to begin a gene therapy-related clinical trial within the United Kingdom (UK) to evaluate LYS-GM101 for patients with juvenile GM1 gangliosidosis.
LYS-GM101 is also known as “adeno-associated viral vector serotype rh.10 expressing beta-galactosidase.” It sits within the adeno-associated viral vector (AAV) arm of gene therapy. According to AskBio, AAV works via a precise mechanism:
The viral DNA is replaced with new DNA, and it becomes a precisely coded vector and is no longer considered a virus, as most of the viral components have been replaced. The AAV vector is then used to deliver normal copies of genes to the right tissues or organs in the body, but it now delivers the therapy that has been engineered into it.
In this case, LYS-GM101 will be directly administered to the cisterna magna at the back of the head. This would hopefully allow for more of the treatment to reach its intended targets. In 2016, LYS-GM101 was granted Rare Pediatric Disease status in America; one year later, it received Orphan Drug designation in both the US and EU.
Juvenile GM1 Gangliosidosis
GM1 gangliosidosis is a rare progressive lysosomal storage disorder that causes neuronal death in both the brain and spinal cord. Because juvenile GM1 gangliosidosis is a genetic disorder, children typically inherit it from their asymptomatic carrier parents, each of which only has one mutated GLB1 gene. An estimated 1 in under 200,000 people has GM1 gangliosidosis.
There are three main forms of juvenile GM1 gangliosidosis: classic infantile (Type 1), late infantile and juvenile (Type 2), and chronic or adult (type 3). The latter category is typically found in people with Japanese heritage.
In infants with Type 1 GM1 gangliosidosis, symptoms or signs are usually not apparent at birth. However, most signs and symptoms will be apparent by age 6. Many patients with type 1 GM1 will not survive past childhood. Symptoms include:
- Enlarged spleen, gums, liver, and heart
- Failure to thrive
- Muscle weakness
- Muscle pain and stiffness
- Cherry-red spots in the eyes
- Being easily startled
- Impaired skeletal functions
In patients with Type 2 GM1 gangliosidosis, development seems normal for the first 15-17 months of life. However, following this time period, development slows down or regresses. Those with this form of GM1 may survive into late childhood or even into their early 20s. Symptoms include:
- Developmental delays and disabilities
- Impaired coordination
- Speech difficulties
Finally, patients with Type 3 GM1 gangliosidosis often have the least severe form of this condition. Symptom severity, and overall survival rate, vary. Symptoms may include:
- Bone and spinal cord irregularities
- Involuntary muscle spasms
- Muscle atrophy
- Vision impairment
Learn more about juvenile GM1 gangliosidosis.