Novel Cell-Based Therapy Shows Promise in Parkinson's Disease

Caroline Cassels

May 07, 2008

May 7, 2008 (Chicago, Illinois) — Four-year results of a pilot study testing a novel cell-based therapy that appears to produce a continuous source of dopamine is showing promise in patients with moderate to advanced Parkinson's disease (PD).

Presented at the American Association of Neurological Surgeons 76th Annual Meeting, the study findings showed a 44% improvement from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) at 48 months in 6 patients who underwent unilateral stereotactic brain surgery to implant human retinal pigment epithelial cells (rHPE).

Found in the inner layer of the retina, rHPE cells produce levodopa, a dopamine precursor. Once implanted in the brain, the levodopa produced by these cells is presumably converted to dopamine, the neurotransmitter that is decreased in PD due to progressive loss of dopaminergic neurons.

"The results are promising. Ultimately we hope that this [therapy] is going to be a long-term, effective way of delivering medication. These cells not only produce levodopa but have receptors on them to control production and the amount of levodopa in the extracellular space," study investigator Roy Bakay, MD, a neurosurgeon at Rush University, in Chicago, Illinois, told Medscape Neurology & Neurosurgery.

"These are not stem cells, they're not embryonic cells, they're not even neurons and don't require immunosuppression. This therapy offers us a way of delivering levodopa in a very smooth and regulated way without the ups and downs you get with oral medication," he added.

No "Runaway" Dyskinesias

Known as Spheramine (Titan Pharmaceuticals, San Francisco, CA) the product consists of rHPE cells, which are attached to gelatin microcarriers. The rHPE cells are derived from donated eyes. According to Dr. Bakay, a single set of eyes has the potential to treat "several hundred" PD patients.

The researchers embarked on the phase 1 pilot study based on positive results from animal research. The primary aim of the open-label study, conducted at Emory University, in Atlanta, Georgia, was to determine safety and tolerance, but it also had efficacy end points, including improvement in motor function based on UPDRS scores. Secondary end points included patient-reported quality-of-life measures.

The study subjects were 3 men and 3 women, all with moderate to advanced PD. The mean age of the patients was 52 years, ranging from 47 to 56 years. The average duration of disease was 8.5 years, with mean Hoen and Yahr scores of 3.8. At baseline, the mean UPDRS score was 118.

Magnetic resonance imaging–guided stereotactic surgery was carried out in a single procedure to facilitate implantation of the rHPE cells in the posterior commissure of the putamen. The cells were injected into 5 tracts for even distribution.

The stereotactic surgery itself was "pretty routine," said Dr. Bakay, and falls within the scope of usual neurosurgical practice. He added that locating the exact site and administering the injections is a "little tricky" but that they are skills that can be readily acquired by a trained neurosurgeon.

Patients were released from the hospital after about 3 days and were then monitored by a neurologist at regular time points over 48 months.

Dramatic Improvement in "On" Time

Dr. Bakay noted there was a dramatic improvement in "on" time without dyskinesias and much less "off" time. This not only represents an advantage over medication but also fetal-cell transplants, which can cause a worrisome phenomenon described as "runaway dyskinesias."

"Fetal-cell transplants appear to produce dopamine at an apparently uncontrolled rate, with the result that you get these uncontrolled dyskinesias, even when you take patients off their medications. We did not observe this side effect in this group of patients," he said.

In addition to improved motor function, patients also experienced a 30% improvement in self-reported quality-of-life scores at the end of the study period compared with baseline.

Adverse effects were limited to transient headache immediately following surgery, which spontaneously resolved within 1 to 2 weeks. Importantly, said Dr. Bakay, there were no adverse effects related to the treatment itself.

The trial has now been extended to 10 years of follow-up. In addition, the positive pilot study results prompted the initiation of a multicenter, double-blind, randomized, sham-surgery–controlled study to further evaluate this treatment in 71 study subjects. The results of this study, known as the STEPS trial, will be available sometime next year.

The study was supported by Titan Pharmaceuticals and Bayer Schering Pharma AG. Dr. Bakay reports that he has consulted for Bayer Schering Pharma AG.

American Association of Neurological Surgeons 76th Annual Meeting: Abstract 544. Presented April 29, 2008.

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