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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."

Co-researchers include Dr. Stefan Worgall, Dr. Dolan Sondhi, Dr. Neil R. Hackett, Dr. Barry Kosofsky, Dr. Minal V. Kekatpure, Dr. Nurunisa Neyzi, Dr. Jonathan P. Dyke, Dr. Douglas Ballon, Dr. Linda Heier, Dr. Bruce M. Greenwald, Dr. Paul Christos, Dr. Madhu Mazumdar, Dr. Mark M. Souweidane and Dr. Michael G. Kaplitt — all from NewYork-Presbyterian/Weill Cornell.

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NewYork-Presbyterian Hospital/Weill Cornell Medical Center

NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances — from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and, most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient. NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit www.med.cornell.edu.