Emory researchers report promising findings in advanced Parkinson's with novel cell therapy

April 01, 2003

HONOLULU -- An investigational surgical cell therapy tested to improve signs and symptoms in advanced Parkinson's disease (PD) patients is showing sustained benefit in motor function, two years following treatment. Emory University researchers report that participants, on average, experienced a 41 percent improvement (range 29-58 percent) in motor function when off other medications and, on average, a 39 percent improvement (range 35-40 percent) in quality of life measures. Ray L. Watts, MD, professor of neurology, Emory University School of Medicine and lead investigator of the study, will present the two-year follow-up findings at the American Academy of Neurology 55th Annual Meeting in Honolulu, Hawaii on April 1.

During a pilot clinical study, Emory University researchers implanted retinal pigment epithelial (RPE) cells attached to microcarriers (Spheramine") into the brains of six patients with advanced PD. The microcarriers are necessary for the cells to survive after implantation, and form the basis for this novel therapy. RPE cells, normally found in the back of the eye, are cultured under standardized conditions to produce cells for this treatment. These cells provide a source of increased dopamine production. Dopamine is a neurotransmitter in the brain that is found in steadily decreasing amounts as PD progresses. The implanted cells serve as a new potential source of dopamine production in these patients.

Parkinson's disease is a progressive neurological disorder that affects a person's ability to move, causing tremor, slowness and stiffness of muscles. Because of the malfunctioning and loss of cells in the brain that make dopamine, most PD treatments are aimed at restoring dopamine deficiency. The longer a patient has the disease, the greater the loss of dopamine-producing cells, requiring an increase in medications, which often leads to side effects. Therefore, new ways to restore dopamine are needed.

"In most cases, Parkinson's patients respond well to medications," says Dr. Watts. "But for those who have been on medications for an extended period of time - say 10 to15 years - their response to medications tends to fluctuate throughout the day. This novel technique can potentially give patients something beyond what we can do with current medications alone."

In this new cell therapy, hundreds of millions of cells are grown in cell culture, and are attached to microscopic gelatin beads (or microcarriers) to create the novel cellular product Spheramine, under development by Titan Pharmaceuticals, Inc. In this pilot study, neurosurgeons implanted approximately 325,000 cells through a needle in five different areas of the striatum, the part of the brain that controls movement, during MRI-guided stereotaxic surgery. The cells can then survive on the microcarriers in the striatum and continually provide a source of increased dopamine production.

Participants showed improvement in their tremor, stiffness, slow movement and balance, the most common motor functions affected by Parkinson's disease, throughout the two-year follow-up period. They also continued improvement in measures of quality of life and activities of daily living.

"The six participants in this pilot study are two years post-treatment," Dr. Watts explains. "The improvements that we saw six to 12 months after implantation, which were promising, have been maintained up to 24 months now, which continues to be encouraging. These data now lead us to move to the next step, a multi-center, controlled, double-blind trial."

In this recently begun phase IIb research study, half of participants will receive Spheramine implanted on each side of the brain and half will receive a "placebo," in which participants will undergo an imitation surgery and will not have any brain surgery or cells implanted. Neither patients nor doctors will know who received the treatment. Only the neurosurgeon will know who received Spheramine. Participants will be followed closely and examined for final results at 12 months. Researchers are looking for efficacy as well as safety measures in this study. Researchers plan to enroll 68 participants in the multi-center study. Emory will serve as one of the neurological and neurosurgical centers.

"In the pilot study, the first human intracerebral retinal cell implantation study, we only implanted one side of the brain for safety reasons and to lessen the potential for complications," says Dr. Watts. "But since Parkinson's disease is a disorder that affects both sides of the brain, the phase IIb study will evaluate bilateral implantation - that is injections of Spheramine into both sides of the brain. Participants will receive a total of 650,000 RPE cells, with 325,000 implanted on each side. So we'll scale up the dose, but not by increasing the amount put into each striatum."

Dr. Watts says this new cell therapy is an important step, but it needs to be evaluated in a further rigorous manner during a controlled, double-blind study, which is now underway. "We're pleased that the improvement has continued out to two years of follow-up, and we hope this new study will also demonstrate significant benefits to PD patients."
-end-
Media Contacts: Janet Christenbury, 404/727-8599, jmchris@emory.edu
Kathi O. Baker, 404/727-9371, kobaker@emory.edu

Emory University Health Sciences Center

Related Dopamine Articles from Brightsurf:

Dopamine surge reveals how even for mice, 'there's no place like home'
''There's no place like home,'' has its roots deep in the brain.

New dopamine sensors could help unlock the mysteries of brain chemistry
In 2018, Tian Lab at UC Davis Health developed dLight1, a single fluorescent protein-based biosensor.

Highly sensitive dopamine detector uses 2D materials
A supersensitive dopamine detector can help in the early diagnosis of several disorders that result in too much or too little dopamine, according to a group led by Penn State and including Rensselaer Polytechnic Institute and universities in China and Japan.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Viewing dopamine receptors in their native habitat
A new study led by UT Southwestern researchers reveals the structure of the active form of one type of dopamine receptor, known as D2, embedded in a phospholipid membrane.

Significant differences exist among neurons expressing dopamine receptors
An international collaboration, which included the involvement of the research team from the Institut de Neurociències of the UAB (INC-UAB), has shown that neurons expressing dopamine D2 receptors have different molecular features and functions, depending on their anatomical localization within the striatum.

How dopamine drives brain activity
Using a specialized magnetic resonance imaging (MRI) sensor that can track dopamine levels, MIT neuroscientists have discovered how dopamine released deep within the brain influences distant brain regions.

Novelty speeds up learning thanks to dopamine activation
Brain scientists led by Sebastian Haesler (NERF, empowered by IMEC, KU Leuven and VIB) have identified a causal mechanism of how novel stimuli promote learning.

Evidence in mice that childhood asthma is influenced by the neurotransmitter dopamine
Neurons that produce the neurotransmitter dopamine communicate with T cells to enhance allergic inflammation in the lungs of young mice but not older mice, researchers report Nov.

Chronic adversity dampens dopamine production
People exposed to a lifetime of psychosocial adversity may have an impaired ability to produce the dopamine levels needed for coping with acutely stressful situations.

Read More: Dopamine News and Dopamine Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.