A new gene therapy that involves injecting a harmless virus into the brain shows promise as a safe and effective way to slow Batten disease, a rare neurological disorder that usually becomes fatal between the ages of 8 and 12.
Children with the disease, also known as Late Infantile Neuronal Ceroid Lipofuscinosis, are born with a mutated CLN2 gene. This causes a deficiency in TTP-1, an enzyme responsible for ridding cells of the central nervous system of waste materials. Parts of the neurons in the brain cell eventually become clogged with toxic material.
"It's like the garbage man of the cell is not able to do its job," study author Dr. Ronald Crystal (pictured), chairman of the Department of Genetic Medicine and chief of the Division of Pulmonary and Critical Care Medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, said in a prepared statement. "The trash keeps getting backed up inside the cell until the cells can no longer function properly and then eventually die throughout the entire brain."
In a clinical trial, neurological surgeons created six tiny holes in the skull of a patient, and then injected into the brain a liquid containing the healthy CLN2 gene within the harmless adeno-associated virus (AAV).
"The virus is used as a Trojan horse that houses and then delivers a healthy, functional gene into the cells of the brain," Crystal said. "The genes are incorporated within the genetic material of the cells, which are then able to produce a protein that is deficient in Batten disease."
In following the patients for 18 months after the procedure, the team found the gene therapy safely and effectively slowed the disease's progression.
"Before now, we had no hope of a therapy for Batten disease, but today, we can say that there is some hope," Crystal said. "These results are not just promising for sufferers of the disease, but suggest that gene therapy can work and should be studied for other neurological disorders. Each gene in our body has the potential to become a target to study for human disease."
Only about 200 cases of Batten disease exist in the world at a given time because of its early fatality rate. Around age 4, children with Batten disease usually start showing symptoms such as impaired muscle coordination (ataxia), involuntary twitching (myoclonus), and speech and developmental disorders. Eyesight then usually begins to decline, and affected children generally become wheelchair-bound, then bedridden.
Illustration: Weill Cornell Medical College.
New York-Presbyterian Hospital/Weill Cornell Medical Center News Release (05/13/08)
Washington Post (05/13/08)
Science Daily (05/14/08)
Cornell University Chronicle Online (05/30/08)
Abstract (Human Gene Therapy; 19, 463-474 (05/01/08))