On July 8, 2021, gene therapy company Lysogene shared that its gene therapy candidate LYS-GM101, for patients with GM1 gangliosidosis, received Fast Track designation from the FDA. Currently, no treatments exist for patients with GM1 gangliosidosis. Thus, if LYS-GM101 was to be approved, it would fulfill an immense unmet need within this patient population. Lysogene is currently evaluating LYS-GM101 within a global adaptative-design clinical trial, in which the first patient has been dosed.
LYS-GM101
According to Lysogene, LYS-GM101 is:
a gene therapy candidate designed to restore the ability of brain and spinal cord cells within the central nervous system (CNS), as well as the cells within the peripheral nervous system, to manufacture functional beta-galactosidase [by using an adeno-associated viral vector to deliver a functional copy of the GLB1 gene]. In patients with GM1 gangliosidosis, initiating long-term expression of beta-galactosidase has the dual effect of removing accumulated GM1-ganglioside lipids and preventing further buildup.
The LYS-GM101 program recently received Fast Track designation, which is granted by the FDA. Requested by the drug developer, Fast Track designation is intended to more quickly develop and review therapies for patients with serious conditions or those fulfilling an unmet need. In this case, filling an unmet need can also consist of showing improvement over an available therapy. Once Fast Track designation is received, drug developers are also eligible for accelerated approval, rolling Biologics License Application (BLA) review, Priority Review status, and increased assistance from the FDA. Beyond Fast Track designation, LYS-GM101 has also received Orphan Drug and Rare Pediatric Disease designations.
GM1 Gangliosidosis
GM1 gangliosidosis is a rare inherited lysosomal storage disorder which causes progressive nerve destruction in the brain and spinal cord. Altogether, GLB1 gene mutations cause GM1 gangliosidosis. Because this condition is inherited in an autosomal recessive pattern, patients must receive one defective gene from each parent to inherit this condition. GLB1 mutations cause beta-galactosidase-1 deficiencies, which causes GM-1 ganglioside to accumulate in cells, causing damage.
GM1 Forms
In Type 1 (classic infantile), symptoms typically appear within around 6 months following birth. Although patients may appear “normal” following birth, they often experience failure to thrive and developmental regression. As the most severe form, many patients do not survive past early childhood. Additional signs and symptoms associated with type 1 GM1 gangliosidosis include:
- Muscle weakness
- Exaggerated startle reflex
- Enlarged gums, spleen, liver, and heart
- Impaired skeletal function
- Cherry-red spots on the eyes
- Seizures
- Corneal clouding
- Pain and stiffness
- Intellectual disability
In type 2 GM1 (late infantile/juvenile), symptoms typically appear by either 18 months (late infantile) or 5 years (juvenile). Similarly, they experience normal development followed by symptoms including developmental regression. These patients may live to late childhood or early 20s. Unlike type 1, type 2 GM1 gangliosidosis is not characterized by enlarged organs or cherry-red spots. Additional symptoms may include:
- Impaired coordination
- Speech difficulties
- Dementia
Finally, type 3 (chronic/adult) GM1 gangliosidosis is considered the least severe form. Many patients experience symptom onset in teen years, with survival rates varying. Symptoms include:
- Bone and spinal cord irregularities
- Dystonia
- Muscle atrophy
- Skin blemishes on the lower trunk
- Corneal clouding
Learn more about GM1 gangliosidosis.
