Jojo, a ten-year-old girl, has become the first person to ever receive a new gene therapy for the treatment of GM1 gangliosidosis. The treatment, called AXO-AAV-GM1, was used in a human clinical trial at the National Institutes of Health in Maryland over the summer. This trial comes after the treatment went through trials of cats who carried the gene for GM1 gangliosidosis. Jojo did not experience any major side effects or complications, which brings hope to the researchers and to those who have this disease.
About GM1 Gangliosidosis
GM1 gangliosidosis is an inherited lysosomal storage disorder that is characterized by the progressive destruction of neurons in the brain and spinal cord. It is a recessive disorder, as both parents must pass down the mutated version of the GLB1 gene. This gene is responsible for the instructions for making an enzyme called beta-galactosidase, which plays an important role in brain function. This enzyme is in the lysosomes, and helps to break down different molecules, including GM1 ganglioside, which affects neuron function. If this substance is not broken down, the accumulation becomes toxic and destroys nerve cells.
There are three types of this disease depending on the age that symptoms present themselves. They are classic infantile, juvenile, and adult onset or chronic. Classic infantile, also called type 1, is the most severe of these types. Symptoms tend to present themselves within six months after birth, but until then development is normal. After the onset, any developmental milestones that have been accomplished will be lost.
Symptoms include neurodegeneration, seizures, enlargement of the liver and spleen, facial features becoming coarse, irregularities within the skeletal system, stiffness in the joints, a distended abdomen, muscle weakness, being overly startled by sound, and issues with walking. Half of those with this type develop red spots in the eyes, and many may become deaf or blind by age one. Children with this type typically do not live past two.
The juvenile form, also referred to as type 2, is an intermediate form of the disease, with the onset of symptoms occurring between one and five. Symptoms include ataxia, seizures, dementia, and issues with speaking. The last type, adult onset or type 3, presents itself anywhere from the ages of three to 30. Symptoms include muscle atrophy, clouding of the cornea, and dystonia. Some people experience skin blemishes on the lower half of the body. This is the least severe form of GM1 gangliosidosis, and it progresses the slowest.
After these symptoms are noticed, a diagnosis can be given through an enzyme analysis or molecular testing of the genes. While the former is more popular for diagnosis, genetic testing is recommended for family members to see if they are carriers of the mutated gene.
At this moment, there is no cure for GM1 gangliosidosis. The symptoms can be treated, but it cannot stop the progression of the disease. Speech and physical therapy is recommended, along with a healthy diet, hydration, and keeping the airway open. There are also medications that can help reduce seizures. There is currently research being done into gene and enzyme therapy as possibilities for treatment.
About AXO-AAV-GM1
AXO-AAV-GM1 is delivered in one IV injection, with the entirety of the treatment taking about an hour. It was developed by Auburn University’s College of Veterinary Medicine and the University of Massachusetts Medical School, after researchers at Auburn have spent several decades improving the lives of cats with GM1 gangliosidosis. It was only recently that they moved to giving this treatment to a human.
They hope to treat three or four more children in the upcoming months in order to better evaluate the effects. This new development brings hope to the lives of those with GM1 gangliosidosis and other lysosomal storage disorders.
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