Cell Implantation Shows Promise and Improvement in Advanced Parkinson's
Disease Patients A One Year Follow-Up
procedure, in which retinal cells are implanted in the brains of patients
with advanced Parkinson's disease (PD), is showing promise, according
to a group of Emory University researchers. In a one-year follow-up
report to be given at the American Academy of Neurology 54th Annual
Meeting in Denver, Colo., on April 17, Ray Watts, M.D., professor of
neurology, Emory University School of Medicine, says patients involved
in this study have improved 30 to 50 percent following treatment. Dr.
Watts will lead the discussion on the safety and efficacy of this pilot
study at the meeting.
In this phase one trial,
Dr. Watts and colleagues implanted retinal pigment epithelial (RPE)
cells, cells found in the back of the eye, into the brains of six patients
with advanced PD. These cells produce L-dopa, a chemical that the brain
uses to make dopamine. Dopamine is a neurotransmitter produced by neurons
in the brain that is found in steadily decreasing amounts as the disease
progresses. The implanted retinal cells serve as a new source of dopamine
production in these patients.
"This is the first human
intracerebral retinal cell implantation study in the world and we are
encouraged by the results so far," Dr. Watts reports. "We've been following
these six participants for over a year, and we've found they've improved,
on average, 30 to 50 percent in various measures of motor function."
Improvement is being seen in their tremor, stiffness, slow movement
and balance, the most common motor functions affected by Parkinson's
disease. Half of the participants are also showing improvement of dyskinesia,
which are involuntary movements that are a result of medications.
The epithelial cells used
in the trial were taken from one human eye donor. Hundreds of millions
of cells were grown in cell culture from the donor cells, and they were
attached to tiny gelatin beads (or microcarriers) prior to implantation.
Surgeons then implanted 325,000 cells in each participant during MRI-guided
stereotaxic surgery. The cells were implanted in five different areas
of the striatum, the part of the brain that controls movement. The cells
then live on the gelatin beads in the striatum, continually making L-dopa.
The novel cell product is called Spheramine®, developed by Titan
Pharmaceuticals, Inc. and uses Titan's cell-coated microcarrier (CCM)
Epithelial cells reproduce
on the surface in which they grow, similar to a layer of skin. Once
the cells have covered the surface, they stop growing, so overproduction
of these cells does not occur. Overgrowth of embryonic stem cells implanted
in the brains of some parkinsonian rodents has raised concern about
the future of that approach. Until this overgrowth has been controlled,
this would not be investigated in humans with PD.
Participants in the Emory
study only had cells implanted on one side of the brain, focusing on
the side that was most affected by the disease. This implantation procedure
is still investigational and has not been approved by the Food and Drug
Administration (FDA) for general use.
Researchers say because it
is performed stereotaxically with a needle, there is less risk of infection
or bleeding. Participants did not have to take immune suppressant drugs,
because the brain is relatively immune protected and these cells appear
to have low tendency to produce an immune response when implanted with
The research for this Phase
I, open-label trial was supported by a grant from Titan Pharmaceuticals,
Inc. and the National Institute of Neurological Disorders and Stroke
(NINDS), a division of the National Institutes of Health (NIH).
"This new cell implantation
therapy appears to be safe and well tolerated in participants 12 to
15 months following implantation," says Dr. Watts. "We will continue
to follow these six participants for months to come. We hope to begin
a Phase II controlled trial soon implanting RPE cells on both sides
of the brain, instead of just one side."
Parkinson's disease is a
progressive disorder of the central nervous system affecting over one
million people in the United States.