Emory physicians test treatment
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.
for Lou Gehrig's disease
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.
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
"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.