The purpose of this trial is to examine the short term effects (6 months) of GM1 on Parkinson’s disease (PD) symptoms, as well as the effects of long-term treatment (2 years) with GM1 on disease progression, and to examine the extent to which GM1 treatment influences the underlying disease process in PD.

The study is designed to further examine the extent to which GM1 ganglioside can improve symptoms, delay disease progression, and, perhaps, partially restore damaged brain cells in PD patients. GM1 ganglioside is a chemical that is normally found in the brain and is a normal part of the outer covering or membrane of nerve cells. This study willl compare the effectiveness of GM1 to standard PD treatment. In addition to studying clinical measures of motor and cognitive functioning, the investigators will use PET (positron emission tomography) scanning to image the brain and the dopamine nerve endings. Patients with mild to moderate idiopathic PD will be divided into 2 groups. One group will receive GM1 for 6 months and the other will receive placebo. At the end of this 6-month period, all patients will enter into a 2-year open extension study in which all patients will receive GM1.

In a parallel study designed to assess the natural progression of PD symptoms as well as the loss of dopamine terminals in the brain, patients with mild to moderate PD will be monitored over a 2-year period. These patients will receive yearly PET scans and biannual clinical evaluations. They will not receive the experimental medication.

Ages Eligible for Study:  39 Years   -   85 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion criteria:

• Between the ages of 39-85 years old.
• If female, one of the following three scenarios must apply: a) at least two years post-menopausal; b) surgically sterile; or c) negative pregnancy test by quantitative serum ßHCG, and following a reliable method of birth control (oral contraceptive, intrauterine device, contraceptive implant, barrier, or abstinence) for at least two months prior to entry, and agreeing both to follow a reliable method of birth control, and (if relevant) to desist from breast feeding during, and for one month following, the period of study drug administration.
• Diagnosis of idiopathic PD, made at least six months prior to screening. The diagnosis shall have required: a) the presence of at least two of the four cardinal clinical manifestations of the disease, which are tremor, rigidity, bradykinesia, and disturbances of posture or gait, without any other known or suspected cause of parkinsonism; and b) at least one of the manifestations must be rigidity or bradykinesia.
• Modified Hoehn and Yahr Staging between 1 and 3, inclusive, as rated during a practically defined “off” period of at least 12 hours.
• Unified Parkinson’s Disease Rating Scale (UPDRS) motor component score between 10 and 40, inclusive, as rated during a practically defined “off” period of at least 12 hours and a score of 6 or greater during the "on" period.
• The following must apply to the antiparkinsonian treatments (also see Exclusion Criterion No. 5): a) stable treatment regimens for l-dopa/carbidopa (benserazide) (regular and/or controlled release preparations) for at least three months prior to Screening, if on that therapy; and b) stable dopamine agonist treatment regimen for the period starting three months before screening.
• Mini Mental State Exam (MMSE) score > 25.
• Beck Depression Inventory score < 10.
• Signed informed consent.

Exclusion criteria:

• Abrupt onset of Parkinsonism.
• Failure of Parkinsonian symptoms to have responded to l-dopa.
• Motor symptoms (such as peak dose dyskinesias (UPDRS score > 3), and random on-off phenomenon), other than end-of-dose wearing-off, persistently fluctuating over a six month or longer period, in response to l-dopa.
• History of findings of any movement disorder other than idiopathic Parkinson’s disease.
• A tremor score on the UPDRS motor scale of >5. Tremor score greater than 3 in an individual limb.
• High-dose vitamin E therapy (more than 1000 I.U./day) any time during the period starting three months prior to the first baseline assessment.
• Transient ischemic attack any time during the period starting six months prior to the first baseline assessment.
• History of two or more strokes (a stroke being defined as cerebral infarction, including lacunar infarction, with clinical signs or symptoms of at least 24 hours duration). History of any stroke that resulted in motor deficit, movement disorder, ataxia, cognitive impairment, or a hemi-inattention syndrome. Any stroke with residua at the time of, or within six months preceding, study entry.
• Previous cerebral infarction, including lacunar infarction, in any area subserving motor function (including pyramidal, extrapyramidal, and cerebellar pathways).
• Binswanger’s disease or a history of hypertensive encephalopathy.
• History of encephalitis.
• History of extended exposure to any known neurotoxin (e.g., manganese, cobalt, MPTP, cyanide, carbon monoxide) that may cause parkinsonism, or chronic or sufficient use or consumption of any non-medicinal substance (e.g., alcohol, heroin) such that there was a significant risk of developing a movement disorder or disturbance of posture or gait.
• Use of the following drugs within six months prior to screening: neuroleptics, metoclopramide, clozapine, flunarizine, alpha-methyldopa.
• Patients actively taking a medicine that is known to compete with the imaging agent for binding sites on the dopamine terminals.
• History of medication or drug use that may have caused atypical parkinsonism or history of Substance Use Disorder, as defined in DSM-IV (formerly Psychoactive Substance Use Disorder in DSM III-R).
• History of a metabolic disorder (e.g., hypoparathyroidism, pseudohypoparathyroidism, Wilson’s disease) that resulted or could have resulted in a movement disorder or disturbance of posture or gait.
• Any disease or condition, other than idiopathic Parkinson’s disease (e.g., essential or familial tremor, cerebellar ataxia, sensory ataxia), that resulted or could have resulted in a movement disorder or disturbance of posture or gait.
• History of intracranial hemorrhage, intracranial neoplasm, significant head trauma with loss of consciousness > 24 hrs, or other structural brain disease.
• History or clinical findings suggestive of progressive supranuclear palsy, or multiple system atrophy (striatonigral degeneration, Shy-Drager syndrome, olivopontocerebellar degeneration, Parkinsonism-amyotrophy syndrome, or intermediate forms).
• Acquired cognitive impairment reasonably possibly due to any cause other than idiopathic Parkinson’s disease.
• History of a hereditary disorder associated with a movement disorder (e.g., Wilson’s disease, Hallervorden-Spatz disease, Huntington’s disease, neuroacanthocytosis).
• Normal or low pressure hydrocephalus.
• Any ill-defined neuropathic disease, myelopathy, myopathy or other medical disorder or physical condition by history or clinical examination, that could reasonably be expected to interfere with the diagnosis, treatment or assessment of Parkinson’s disease, or with any of the study assessments.
• History of Guillain-Barré syndrome, chronic idiopathic polyneuropathy, or relapsing polyneuropathy.
• History of Axis I or Axis II major psychiatric disorder.
• Significant cardiac, pulmonary, hepatic, gastrointestinal, or renal disease (e.g., New York Heart Association Class III or IV congestive heart failure; endocarditis; pulmonary insufficiency symptomatic at rest or with mild physical exertion; acute or chronic hepatitis; renal failure requiring dialysis; second and third degree AV block or sick sinus syndrome).
• Any condition, as determined by history, examination, or laboratory investigation that could: a) alter the distribution, accumulation, metabolism, or excretion of the study medication; or b) result in a life expectancy of less than two years.
• Any primarily non-neurologic medical condition (e.g., paroxysmal atrial fibrillation) with a significant risk of secondarily causing neurologic dysfunction.
• Myocardial infarction within 6 months prior to screening.
• Presence of any medical condition, or laboratory test abnormality, or use of any licit or illicit substance, which can reasonably be expected to subject the patient to unwarranted risk from participation in the study, or result in clinically significant worsening in the patient’s medical condition during the time course of the trial. Presence of any of the following laboratory test abnormalities shall be deemed to represent an unwarranted risk to enter the study: serum transaminase (ALT/SGPT, or AST/SGOT) greater than twice the upper limit of normal; serum creatinine greater than 2.0 mg/dl in a man, or greater than 1.7 mg/dl in a woman.
• History of a life-threatening allergic or immune-mediated reaction.
• Previous use of any ganglioside preparation (e.g., Sygen®, Cronassial®, Sinassial®).
• Use of any experimental drug in the period starting 60 days preceding the first Baseline assessment.
• History of stereotaxic brain surgery for PD.