PARKINSON’S Highlights – Recent Data
Celavie has targeted Parkinson’s disease (PD) as the first human application of its stem cells (OK99). Parkinson’s disease (PD) is a chronic and progressive movement disorder, meaning that symptoms continue and worsen over time. Nearly one million people in the US are living with Parkinson’s disease. The risk of developing Parkinson’s is about 1 percent at age 60. The cause is unknown, and although there is presently no cure, there are treatment options such as medication and surgery to manage its symptoms.
Parkinson’s involves the malfunction and death of vital nerve cells in the brain, called neurons. Parkinson’s primarily affects neurons in an area of the brain called the substantia nigra. Some of these dying neurons produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. As PD progresses, the amount of dopamine produced in the brain decreases, leaving a person unable to control movement normally.
The specific group of symptoms that an individual experiences varies from person to person. Primary motor signs of Parkinson’s disease include the following. One year follow up after implantation of stem cells into brains of parkinsonian patients revealed no detectable immune response, side effects, or complications attributable to the procedure.
The Phase I (safety) study was approved by Federal Commission for Protection against Sanitary Risks – Mexican equivalent of FDA (COFEPRIS) and is being conducted in Mexico City at Hospital Angeles Pedregal and.
The study is registered at cliniclatrial.gov website.
Eight patients with moderate to severe PD that was not adequately controlled with medication were selected for the study. The stem cells were injected into putamen – the structure of the brain that is depleted by PD the most – on both sides of the brain. Patients were immunosuppressed with Cyclosporine for 1 month after injection. Implantation of OK99 was intended to address the underlying pathology of the Parkinson’s disease by replacing damaged/destroyed cells of the brain, and/or stimulating the patient’s brain to repair itself.
The primary end measure is safety: number and severity of side effects and complications
The secondary end measures include variable neurological, neuropsychological and radiological evaluations (Positron Emission Tomography – PET) established in Core Assessment Program for Intracerebral Transplantations (CAPIT) and recognized internationally. These evaluations were performed during on and off medication conditions at baseline, six month, and one year after transplantation. They will be repeated at two and three year after transplantation. The first time the patients were examined with PET using 3 radiomarkers (before only one marker was used) to fully evaluate molecular changes in the brain after transplantation.
One year after transplantation no stem cell related complications or side effects were observed. All but one of the seven patients completing the study showed motor improvement, and five improved responses to medication on the Unified Parkinson’s Disease Rating Scale (UPDRS). Positron Emission Tomography (PET) imaging (using [11C] raclopride, (+)-alpha-[11C] dihidrotetrabenazine, and 6-[18F] fluoro-L-DOPA), showed a trend towards improvement with no evidence of disease progression. Cognitive performance remained unchanged from baseline.
Based on one year follow-up data Celavie is preparing a complete briefing package for FDA to request approval for performing Phase II trial in the USA
Phase II trial is being planned as randomized, single blinded study in which 20 patients with advanced to moderate PD will receive bilateral implantations of undifferentiated OK99 into putamina and 20 patients will serve as controls. All independent raters will be blinded to the condition of the patient
The primary end measure is safety: number and severity of side effects and complications
The secondary end measures include variable neurological, neuropsychological and radiological evaluations (Positron Emission Tomography – PET) established in Core Assessment Program for Intracerebral Transplantations (CAPIT). These evaluations will be performed during on and off medication conditions at baseline, six month, one, two and three years after transplantation.
The Phase II study will be performed at the Hoag Memorial Hospital Presbyterian that has the state-of-the-art neurosurgical facility with the team of highly experienced neurosurgeons, neurologists, neuropsychologists and radiologists. The facility has the most modern stereotactic equipment, CAT scan, MRI, Positron Emission Tomography
