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Updated: Aug 23, 2026
A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS
Published on: October 6, 2015
Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid
Chandrasekaran Raman1, Sean D McAllister, Gulrukh Rizvi
1Forbes Norris MDA/ALS Research Center, 2351 Clay Street, Suite 416, California Pacific Medical Center, San Francisco, CA 94115, USA.
Abstract:
Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. There is rapidly emerging evidence that the cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective if administered either before or after onset of signs in the ALS mouse model (hSOD(G93A) transgenic mice). Administration at the onset of tremors delayed motor impairment and prolonged survival in Delta(9)-THC treated mice when compared to vehicle controls. In addition, we present an improved method for the analysis of disease progression in the ALS mouse model. This logistic model provides an estimate of the age at which muscle endurance has declined by 50% with much greater accuracy than could be attained for any other measure of decline. In vitro, Delta(9)-THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, Delta(9)-THC is anti-excitotoxic in vitro. These cellular mechanisms may underlie the presumed neuroprotective effect in ALS. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.
Insights
Delta(9)-tetrahydrocannabinol (Delta(9)-THC) shows promise for treating amyotrophic lateral sclerosis (ALS). This cannabinoid delayed motor decline and extended survival in an ALS mouse model, suggesting neuroprotective potential.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Amyotrophic lateral sclerosis (ALS) lacks effective treatments.
- Motor neuron vulnerability in ALS is linked to excitotoxicity and oxidative stress.
- The cannabinoid system shows potential for mitigating these damaging processes.
Purpose of the Study:
- To investigate the therapeutic potential of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in an amyotrophic lateral sclerosis (ALS) mouse model.
- To explore the neuroprotective mechanisms of Delta(9)-THC against excitotoxicity and oxidative damage in vitro.
- To develop an improved method for analyzing disease progression in ALS mouse models.
Main Methods:
- Administration of Delta(9)-THC before and after symptom onset in hSOD(G93A) transgenic mice (ALS model).
- Assessment of motor impairment, survival rates, and disease progression.
- In vitro studies using spinal cord cultures to evaluate Delta(9)-THC's effects on oxidative damage and excitotoxicity.
- Development of a logistic model for accurate estimation of disease progression milestones.
Main Results:
- Delta(9)-THC administration delayed motor impairment and prolonged survival in the ALS mouse model.
- In vitro, Delta(9)-THC significantly reduced oxidative damage and demonstrated anti-excitotoxic effects in spinal cord cultures.
- An improved logistic model accurately estimated disease progression by predicting the age of 50% muscle endurance decline.
Conclusions:
- Delta(9)-THC exhibits neuroprotective effects in an ALS mouse model, potentially through reducing oxidative stress and excitotoxicity.
- Cannabinoids, including Delta(9)-THC, represent promising therapeutic targets for amyotrophic lateral sclerosis treatment.
- The developed logistic model offers a more accurate tool for evaluating disease progression in ALS research.
