Parkinson's disease (PD) is a slowly but relentlessly progressive neurodegenerative disorder resulting in a time-dependent worsening of clinical symptoms. No drug has yet been identified that definitively slows or stops the progression of PD or substantially forestalls the inevitable functional decline in PD patients. Thus, disease modifying drugs that can modify clinical progression, enhance repair of damaged neurons, remediate existing neuropathological deficits, restore or enhance function of residual parts of the dopamine (DA) system and/or activate compensatory mechanisms are sorely needed. GM1 ganglioside may be such a treatment. In vitro and in vivo studies have shown GM1 to rescue damaged DA neurons, stimulate survival and repair of DAergic neuron and sprouting of functional DAergic terminals, increase DA levels in the striatum and upregulate DA synthetic capacity of residual neurons. Preliminary clinical studies of GM1 in PD patients have shown clinical improvements in patients with short-term use of GM1 and minimal symptom progression in patients with 2 to 5 years of GM1 use with resumed progression of symptoms following discontinuation of long-term GM1 use. ? ? The specific aims of this research are: ? 1) Assess the clinical efficacy of GM1 and the relationship between clinical improvement and in vivo quantitation of the integrity of the striatal DAergic innervation (assessed by PET imaging of the dopamine transporter site) in patients with typical mild/moderate PD in a randomized double blind placebo-controlled clinical trial. Working hypothesis: GM1 ganglioside treatment will result in symptomatic improvements related to effects on damaged but viable DA neurons and this may be accomplished through sprouting of functional DAergic terminals in the striatum. ? 2) Assess the extent to which long-term (2 years) use of GM1 ganglioside may stabilize symptoms or slow symptom/disease progression in PD patients (using clinical evaluations and PET imaging of the dopamine transporter as a surrogate measure). Working hypothesis: Long-term GM1 use will stabilize symptoms or slow the progression of symptoms in PD patients and this may be accompanied by reduced loss of striatal DA terminals over time. ? ?
| Schneider, Jay S; Cambi, Franca; Gollomp, Stephen M et al. (2015) GM1 ganglioside in Parkinson's disease: Pilot study of effects on dopamine transporter binding. J Neurol Sci 356:118-23 |
| Schneider, Jay S; Sendek, Stephanie; Yang, Chengwu (2015) Relationship between Motor Symptoms, Cognition, and Demographic Characteristics in Treated Mild/Moderate Parkinson's Disease. PLoS One 10:e0123231 |
| Schneider, Jay S; Gollomp, Stephen M; Sendek, Stephanie et al. (2013) A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients. J Neurol Sci 324:140-8 |
| Schneider, J S (2007) Behavioral persistence deficit in Parkinson's disease patients. Eur J Neurol 14:300-4 |
