NYP/Weill Cornell gene therapy clinical trial yields promising results for Batten disease

Promising results from a team of NewYork-Presbyterian Hospital/Weill Cornell Medical Center physician-scientists show that gene therapy is both safe and effective at slowing the progression of Batten disease, or Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL), a rare, genetic, degenerative neurological disorder that usually becomes fatal in children by the age of 8 to 12. The clinical trial found that the procedure -- which involves injecting a harmless gene-bearing virus into the brain -- was not only safe, but, on the average, significantly slowed the disease progression of the subjects tested. Neurological function was assessed using a rating scale throughout an 18-month follow-up period.

"The virus is used as a Trojan horse that houses and then delivers a healthy, functional gene into the cells of the brain," says lead author Dr. Ronald Crystal, 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. "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."

Dr. Crystal is a world leader and pioneer in the use of gene therapy to treat a number of genetic disorders and diseases.

The results are published in the May 13 online issue of Human Gene Therapy.

The gene in question -- CLN2 -- is mutated in children with the disease, causing a deficiency in the enzyme TTP-1, which is responsible for ridding cells of the central nervous system of waste materials. Small organelles within the cell, called lysosomes, become clogged with toxic material within the neurons of the brain.

"It's like the garbage man of the cell is not able to do its job," says Dr. Crystal. "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."

When this happens, children with the disease begin exhibiting neurological symptoms, starting around age 4, including impaired muscle coordination (ataxia), involuntary twitching (myoclonus), and speech and developmental disorders. A gradual decline in visual ability follows. Affected children generally become wheelchair-bound by the ages of 4 to 6 years and eventually become bedridden.

Because the disease is fatal early in life, there are only about 200 cases of the disease in the world at a given time. Subjects from around the world were carefully selected to take part in the trial.

Neurological surgeons from NewYork-Presbyterian Hospital/Weill Cornell Medical Center, led by Drs. Mark Souweidane and Michael Kaplitt, performed the gene therapy procedure. Six tiny holes were made in the skull of each subject, and then a liquid containing the healthy CLN2 gene, within the harmless adeno-associated virus (AAV), was injected into the brain.

"Before now, we had no hope of a therapy for Batten disease, but today we can say that there is some hope," says Dr. Crystal. "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."

Source: New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College