Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/GM1

"In a recent trial, the Parkinson's symptoms of a small number of patients treated with GM1 were observed to have reduced significantly. Some earlier work and some experiments with animal models suggested that GM1 has considerable neuroprotective and restorative properties.  Further information is required on what further work is being done on this apparently promising substance."

Background
GM1 (monosialotetrahexosylganglioside) is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain.

The diseases known as GM1 gangliosidoses are caused by a deficiency of beta-galactosidase, with resulting abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells.

Research
1995

Shneider et al observed the effects of treating mice, which had induced Parkinsonism through treatment with MPTP, with GM1.

"The effect of GM1 on dopamine synthesis was dependent upon the degree of initial damage to the nigrostriatal dopamine system. That is, the GM1 effect on dopamine synthesis could not be demonstrated in mice with greater than 95% striatal dopamine loss and 75% substantia nigra dopamine neuron loss. These results suggest that in addition to previously reported effects of GM1 on rescue and repair of dopaminergic neurons, GM1 may also have the ability to enhance dopamine synthesis in residual dopaminergic neurons. Direct effects on dopamine neurochemistry may contribute to functional improvement seen after GM1 treatment in various models of parkinsonism."

Schneider et al gave GM1 or a placebo to 45 patients with mild to moderate PD. After three independent baseline assessments, patients received IV infusion of the test drug (1,000 mg GM1 or placebo) and then self-administered either GM1 or placebo twice daily (200 mg/day, subcutaneously) for 16 weeks. GM1-treated patients had significantly greater mean improvements than placebo-treated patients in performance of timed motor tests including tests of arm, hand, and foot movements, and walking. GM1 was well tolerated and no serious adverse events were reported.

"This study demonstrates that GM1 ganglioside treatment enhances neurologic function significantly in PD patients. Further study is warranted to evaluate long-term effects of GM1 in PD patients and to elucidate further the mechanisms underlying patient improvements."

1998

Rothblat and Schneider studied the effects of GM1 on MPTP treated mice.

" Results showed that measures of dopamine innervation were significantly increased in most striatal areas in MPTP+GM1-treated mice compared to MPTP+saline-treated controls. The results indicate that GM1 treatment increases measures of dopaminergic innervation after an MPTP lesion, possibly through sprouting of new terminals or increased dopamine production and release from remaining terminals."

Schneider reviewed the results of clinical trials of GM1 on PD patients.

"In a double-blind placebo-controlled study, significant improvements in GM1-treated patients were demonstrated in clinical motor ratings, timed tests of motor function, activities of daily living, and some aspects of neuropsychological functioning. Patients who have elected to continue using GM1 in an open extension trial have either continued to improve over time or have shown initial functional improvements and their disease has remained stable (i.e., no symptom progression) after two years. These results suggest that long-term use of GM1 is safe and may work to partially reverse the degenerative process in established Parkinson's disease patients."

2002

Zappia et al set out to determine whether anti-GM1 antibodies are increased in Parkinson's disease (PD). Conclusion:-

"A consistent portion of parkinsonians, mainly with a tremor-dominant form of PD, may have increased circulating IgM anti-GM1 antibodies."

2010

Schneider et al reported that in earlier studies it was noted that treatment of PD patients with GM1 ganglioside over a period of 16 weeks resulted in a significant reduction in their PD symptoms.

26 PD patients then volunteered to take part in an open-ended double blind placebo controlled extension of the initial trial. At the end of 5 years their PD symptoms were measured and found to be lower than at the start of the trial. The finding was that long term treatment of PD patients with GM1 ganglioside was neuroprotective with no adverse side effects