Newswise — It is estimated that 60,000 new cases of Parkinson's disease (PD) are diagnosed each year, adding to the estimated one to 1.5 million Americans who currently have the disease. The latest epidemiology studies indicate that worldwide numbers will increase from an estimated 4.1 million in 2005 to 8.7 million people with PD by 2030. There were an estimated 19,500 PD-related deaths in the United States in 2005, an increase of 1,500 deaths from 2004.
Early in the disease, there is a loss of brain cells that produce the chemical dopamine. Normally, dopamine operates in a delicate balance with other neurotransmitters to help coordinate the millions of nerve and muscle cells involved in movement. Without enough dopamine, this balance is disrupted, resulting in tremor (trembling in the hands, arms, legs and jaw); rigidity (stiffness of the limbs); slowness of movement; and impaired balance and coordination " the hallmark symptoms of PD.
Despite therapeutic advances, there remain substantial limitations to currently approved therapies for the treatment of PD and new approaches are needed. Spheramine® is a novel cell-based therapy with promise for the treatment of moderate to advanced PD. It consists of human retinal pigment epithelial (hRPE) cells attached to a Microcarrier Support Matrix (MSMTM) for enhanced hRPE cell survival. These cells are found in the inner layer of the retina and produce levodopa. Spheramine is implanted in the brain where the levodopa created by hRPE cells is presumably converted into dopamine, the neurotransmitter that is decreased in PD due to a progressive loss of dopaminergic neurons.
A pilot study was initiated at Emory University Hospital on six patients with moderate to advanced PD to investigate the safety, tolerability, and efficacy of Spheramine implantation. The results of this study, Intrastriatal Implantation of Human Retinal Pigment Epithelial (hRPE) Cells Attached to Gelatin Microcarriers (GM) for the Treatment of Parkinson's Disease (PD), will be presented by Roy A.E. Bakay, MD, of Rush University, 4:51 to 5:00 p.m. on Tuesday, April 29, 2008, during the 76th Annual Meeting of the American Association of Neurological Surgeons in Chicago. Co-authors are Michael Cornfeldt, Alan Freeman, MD, Elke Reissig, MD, and Raymond L. Watts, MD.
Patient selection was based on disease stage, levodopa responsiveness, and severity of PD symptoms while off medication. MRI-guided stereotactic surgery was carried out in a single procedure to implant Spheramine in the most affected side of the brain. A needle was used to implant Spheramine in the motor region of the putamen, an area that is important in the development of PD, to provide a targeted source of levodopa. The implantation procedure involved injection of Spheramine into five tracts for even distribution of cells. Patients were generally discharged within 1 to 3 days. The following methodology was followed:
The primary efficacy measure used in this trial was the motor score of the Unified Parkinson's disease Rating Scale (UPDRS) with the patient OFF antiparkinsonian medication for at least 12 hours. Secondary efficacy variables included patient-reported quality of life measures. Clinical improvements were noted in both UPDRS motor scores off medication (44 percent improvement from baseline at 48 months) and patient-reported quality of life scores (23 percent improvement from baseline of total PDQ-39 score at 48 months). The full patient group has been evaluated for four years, and several have been monitored for six years. The trial has been extended to 10 years follow-up. Additional study findings:
"¢There was long-term improvement or stabilization of symptoms, maintained for a minimum of two years after Spheramine implantation."¢No Spheramine-related serious adverse events were reported. "¢The most frequent adverse event was postsurgical headache, which spontaneously resolved within 1-2 weeks.
"The results of this study are very encouraging " Spheramine is well tolerated through several years of follow-up and improvement in parkinsonian symptoms is sustained," stated Dr. Bakay.
Positive results in the pilot study prompted the initiation of a multicenter, double-blind, randomized, sham surgery-controlled study (STEPS) to further evaluate the safety and efficacy of Spheramine implantation. The design of this related study, The STEPS Trial: Design of a Phase 2 Study to Evaluate Spheramine®, A Novel Cell-Based Therapy Administered by Stereotactic Implantation into the Striata of Patients with Parkinson's Disease (PD), will also be presented on Tuesday, April 29, 3:51 to 4:00 p.m. by Robert E. Gross, MD, PhD. Co-authors are Dr. Bakay, Wilhelm Eisner, MD, Robert Hauser, MD, Walter Hong, Heinz Reichmann, MD, Elke Reissig, MD, Heike Steiner, Raymond L. Watts, MD, and the Spheramine Study Group.
Changes from the pilot study included implantation in both sides of the brain and the addition of a sham surgery group. In sham patients, skin incisions and burr holes through the skull were made but there was no penetration of the dura mater, the outermost layer of membranes protecting the brain. This procedure is less invasive than Spheramine implantation and keeps the patients from knowing what surgery they received. To date, 71 patients have been randomized between Spheramine implantation and sham surgery. Efficacy results are expected later this year. "The results of this trial are expected to provide further evidence of the safety and efficacy of Spheramine implantation," added Dr. Bakay.
Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 7,200 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.
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