Jahnavi Sarma
... Read More
By clicking “Accept All Cookies”, you agree to the storing of cookies on your device to enhance site navigation, analyze site usage, and assist in our marketing efforts. Cookie Policy.
Children with Krabbe disease experience progressive neurological symptoms, including blindness, deafness, and paralysis. @Shutterstock
In one out of 100,000 infants, a mutation in the GALC gene causes an incurable and fatal disorder known as infantile Krabbe disease. It may also be known as globoid cell leukodystrophy. Most children with the condition die before they turn 2. A parallel condition also naturally affects dogs, who typically show symptoms of the disease at six weeks old and succumb to it within a few months. A new study in the Journal of Clinical Investigation (JCI), led by the School of Veterinary Medicine's Charles Vite, describes an effective gene therapy for Krabbe disease in dogs with lasting impact. Dogs that received the treatment have lived to 4 years of age and beyond with no significant symptoms. The work highlights the potential for a similar treatment approach in children.
According to researchers, this disease has no good therapy. A bone marrow transplant within the first month of life can prevent symptoms from arising in about 30 per cent of infants, but the procedure is exceedingly risky. Researchers say that a new treatment is really needed. To blunt the effects of the disease, the researchers knew that getting a healthy version of the GALC gene to the brain was crucial. They were able to make progress in doing so by using a particular vector to deliver GALC gene, the AAV9 vector, which has been used effectively in experimental gene therapies for other neurological diseases and appears the best candidate for FDA approval.
Researchers injected into the spinal fluid via the back of the head, which is the most effective means of getting to the brain. They used both a high and low dose of the gene therapy, administering it to dogs that were two weeks old, before symptoms appear, or six weeks old, after neurological symptoms had begun to emerge.
Dogs that received the high dose gene therapy before the onset of symptoms not only had healthy myelination in their brains, but the gene therapy also maintained myelination of the peripheral nervous system. These dogs have also lived symptom-free for upward of four years. Even dogs treated after they began to show symptoms lived significantly longer with the therapy than without it. The lower dose of gene therapy, however, resulted in an intermediate form of the disease, underscoring the importance of pinpointing the correct dose when translating the findings to children.
Krabbe disease is among a group of conditions known as lysosomal storage diseases, characterized by a buildup of materials in small containers called lysosomes within cells. Normally, the GALC gene encodes an enzyme that breaks down lipids in the body. In Krabbe disease, the mutated GALC causes lipids to build up, resulting in deformed growth of the lipid-containing coating of nerve cells, the myelin sheath, leading to impaired nerve cell signaling. As a result, children with Krabbe disease experience progressive neurological symptoms, including blindness, deafness, and paralysis.