Emory physicians test treatment
for Lou Gehrig's disease

A new means of delivering experimental drugs to the brain that bypasses the blood-brain barrier is being tested at Emory on patients with Lou Gehrig's disease and at five other sites nationally.

Joey Dixon, 44, of Greenville, S.C., is the first patient with Lou Gehrig's disease at Emory and the second worldwide to receive Glial Cell-Derived Neurotrophic Factor (GDNF) in treating the disease via the new device.

Lou Gehrig's disease is the familiar name for the most common degenerative motor neuron disease, amyotrophic lateral sclerosis (ALS), which is said to affect five to 10 people out of every 100,000.

An exciting
breakthrough
Last month Emory neurosurgeon Nelson Oyesiku implanted a permanent device into Dixon's brain that will serve as the port through which GDNF may be periodically delivered. The Phase I clinical trial in which the patient is enrolled will evaluate both the tolerability of GDNF, developed by Amgen, and the effectiveness of the implanted device, which was developed by Medtronics Inc.

"This delivery system is the most exciting thing to happen in ALS research in quite some time," said Jeffrey Rosenfeld, an assistant professor of neurology in the School of Medicine who specializes in ALS treatment and research. He is principal investigator of the trial's Atlanta component. "GDNF is aimed at delaying or halting the degeneration of motor nerve cells, which characterizes ALS," Rosenfeld explained.

GDNF is a growth factor that was first characterized in 1993 as having significant therapeutic potential in ALS and Parkinson's disease. It is a protein isolated from humans and produced in E. coli bacteria cells containing the DNA that expresses the human protein. The recombinant protein injected into patients has an identical amino acid sequence to the native human GDNF protein.
The Medtronic device is surgically implanted into the region of the brain known as the right lateral ventricle. A catheter is placed so that a port lies just underneath the scalp that can be accessed for injections. During the trial, the first injection is administered on an inpatient basis, but patients receive subsequent injections as outpatients. If successful, the system might also be used to deliver drugs for other neurological conditions such as Parkinson's and Alzheimer's diseases.

"The device is implanted using a computer-guided stereotaxtic device under local anesthesia," said Oyesiku. "The procedure is relatively painless-the actual operating time is less than one hour-and the patient can usually be sent home the next day. The incision is concealed behind the hair line, and sutures can be removed in about two weeks."

Although he has been involved in the investigation of other ALS agents, Rosenfeld said he is particularly optimistic about the current trial for two reasons: first, GDNF promoted the survival of motor nerve cells that otherwise would have died when tested in animals, and second, the Medtronic delivery system allows for the injection of the drug directly into the brain's cerebrospinal fluid, thus circumventing the blood-brain barrier.

Only one drug approved
for ALS treatment
Emory neurologists have participated in several major studies of ALS agents, including the later development stages of Riluzol (rilutek), and clinical trials of Ciliary Neurotrophic Factor (CNTF) and Brain-Derived Neurotrophic Factor (BDNF). In addition to participation in the Amgen GDNF trial, the researchers expect to begin investigating another novel growth-promoting factor in 1997-98.

The Emory team will be enrolling five ALS patients into this Phase I part of the study; 24 will participate nationwide.

Each year Emory neurologists treat about 275 ALS patients from across the Southeast. ALS selectively and progressively deteriorates nerve cells in the brain and spinal cord that control motor functions such as walking, talking and breathing. The condition is fatal and has no cure.

Currently, Riluzol is the only drug approved for ALS treatment by the Food and Drug Administration. Riluzol has been shown to have only a modest effect, prolonging by about three months the time patients have to breathe without assistance before requiring a ventilator.

In addition to treatment with Riluzol, patients here at Emory can receive pulmonary evaluation and treatment, nutritional evaluation and treatment, access to occupational and physical therapy, and psychological services to assist them and their families in coping with the disease.

ALS can be inherited (in about 10 percent of patients) or acquired, and the mean survival rate is between two to five years; up to about 10 percent of those with ALS survive longer.

Famed New York Yankee first baseman Lou Gehrig died in 1941 of the disease that later took his name. Before ALS struck, Gehrig tallied 493 home runs, 23 career grand slams and played in a record 2,130 consecutive games over 14 seasons. He stopped playing just two years before his death.

-Lorri Preston


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