Jefferson Neurosurgeons Use Gene Therapy to Treat Rare, Inherited Brain Disease

As a result of their team's innovative research in gene therapy, neurosurgeons are treating a 4-year-old Illinois girl at Thomas Jefferson University Hospital for Canavan disease, a rare, incurable brain disorder fatal to young children between ages 5 and 7.

The Jefferson Medical College (JMC) scientists are hoping the new form of treatment provides some relief for the young patient, as well as insights to future uses of gene therapy for other illnesses. As part of clinical trial studies, they plan to treat a total four children with Canavan disease by using gene therapy for the first time.

The neurosurgeons and neuroscientists include Andrew Freese, MD, PhD; Matthew During, MD; Paola Leone, PhD; and Giancarlo Barolat-Romana, MD, as well as colleagues at Jefferson and at Yale University.

What is Canavan Disease?

Canavan disease predominantly affects children of Eastern European or Ashkenazi Jewish background and usually proves fatal. Inherited, it is a neurological disorder characterized by spongy degeneration of the brain.

The disease is one of a group of genetic disorders called leukodystrophies that affect growth of the myelin sheath of the brain's nerve fibers. The myelin sheath is a fatty covering that surrounds the nerve cells and acts as an insulator. The disease is caused by a genetic flaw which stops a critical enzyme from being produced.

Canavan disease is similar to Tay-Sachs disease in that both are metabolic disorders causing buildup of toxic compounds that affect normal brain development.

Symptoms of Canavan disease, which appear in early infancy and progress quickly, may include mental retardation, loss of previously acquired motor skills, difficulty feeding, abnormal muscle tone, poor head control, and an abnormally enlarged head. As time progresses, the symptoms gravely worsen.

"Children fail to meet normal developmental milestones," Dr. Freese explains. "Within a year, they cannot feed themselves, speak, walk, or see well."

Developing the Therapy

Dr. Freese explains that, three years ago, families with children who had Canavan disease contacted his colleagues at Yale seeking their expertise in gene therapy to develop a therapy for the disease. Drs. During, Leone and Freese went on to develop a preliminary method for delivering genetic information about the critical missing enzyme into the brains of two children with Canavan disease.

In the clinical trial studies at Jefferson, the therapy involves implanting a reservoir and catheter under the patient's scalp, allowing access to the brain's ventricles and fluids.

The Jefferson researchers are collaborating with specialists at Children's Hospital of Philadelphia to monitor the therapy's.success.

"We anticipate expanding our gene therapy approach to other inherited metabolic disorders, such as Krabbe disease," he notes, together with David A. Wenger, PhD, Professor of Medicine, JMC, who leads the Lysosomal Disease Testing Laboratory. "We hope to set up a clinical trial for that within the next year or two as well."

While Dr. Freese cautions that few patients have been treated this way as yet, he hopes that "The results from this trial may give us some information about the possibility of treating other neurological disorders, such as other inherited diseases, and Parkinson's disease, stroke and epilepsy."