An experimental gene therapy had positive effects in slowing the progression of Batten disease, or Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL), a team of New York-Presbyterian Hospital/Weill Cornell Medicine Center physician-scientists showed.

LINCL is an autosomal recessive disease caused by mutations in the CLN2 gene resulting in functional defects of the gene product tripeptidyl-peptidase I. This disease is associated with a progressive neurodegenerative course beginning at the age of two years with developmental stagnation, finally leading to a complete loss of motor function, vision and speech by the age of 10 years.

The disease is diagnosed via DNA testing and strikes two to four of every 100,000 babies in the U.S., according to the National Institutes of Health. Because the disease is fatal early in life, there are only about 200 cases of the disease in the world at a given time.

The disease usually becomes fatal in children by the age of 8 to 12. Around age 4, children with the disease usually start showing symptoms such as impaired muscle condition (ataxia), involuntary twitching (myoclonus) and speech and developmental disorder. Children then generally become wheelchair-bound, then bedridden.

Ronald Crystal and colleagues from Weill Cornell Medical College chose 10 children from the U.S., Britain, Australia and Germany, five severely affected by the disease and five moderately affected. They created six tiny holes in their skull, 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. 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,” Crystal reported in a paper entitled “Treatment of Late Infantile Neuronal Ceroid Lipofuscinosis with CNS Administration of a Serotype 2 Adeno-associated virus expressing the CLN2 cDNA,” published in the May 13 online issue of Human Gene Therapy.

The scientists followed the 10 children for 18 months, comparing them to four untreated children with the same condition, and found the gene therapy safely and effectively slowed the disease’s progression in eight children. One child suffered an epileptic seizure 49 days after the procedure and died, while another child died of unknown causes two years after treatment.

“Before now, we had no hope of a therapy for Batten disease, but today we can say that there is some hope. 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,” Crystal said in the paper.