Category: Neuropharmacology
Objective: Demonstration of beneficial effects of neuro-inflammation inhibition for the treatment of amyotrophic lateral sclerosis (ALS).
Background: Neuro-inflammation and immune-inflammatory processes are characteristics of the ALS pathology and are observed in the brain stem and spinal cord of ALS cases, and in transgenic mouse models of mutant SOD1-associated familial ALS [1,2]. Initially, we found for an orally available compound in an Alzheimer’s disease animal model surprisingly high efficacy towards inhibition of neuro-inflammation. Therefore, we investigated its therapeutic potential in several therapeutic studies in the SODG93A transgenic mouse model of ALS.
Method: SOD1G93A mice and their non-transgenic littermates were treated in several therapeutic studies with different ages at treatment start and varying treatment durations. Treatment was done orally or using i.p. pumps. Animals were tested longitudinally in different behavioral and motor coordination tests.
Results: The compound led to significant improvement in treated SOD1G93A mice. Depending on treatment start, we observed either stop of disease progression or at least very significantly improved performance in the SHIRPA test of transgenic mice compared to placebo controls and a slower neurodegenerative phenotype shown in different motor coordination tests (P < 0.001) as well as retardation of the average disease onset (P <0.001). The treated non-transgenic mice showed the same normal behavior as the untreated non-transgenic controls.
Conclusion: In conclusion, these findings qualify the compound to be considered for further development and testing towards a disease modifying ALS treatment.
References: [1] A. Jeyachandran et al., Front. Cell. Neurosci. 9:462, (2015) [2] A.G. Barbeito, P. Mesci and S. Boillée, Neural. Transm. 117:981, (2010)
To cite this abstract in AMA style:
J. Post-Schulz, A. Schaffrath, A. Willuweit, D. Willbold, J. Kutzsche. Oral treatment of the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS) with the neuro-inflammation inhibiting compound PRI-003 [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/oral-treatment-of-the-sod1g93a-transgenic-mouse-model-of-amyotrophic-lateral-sclerosis-als-with-the-neuro-inflammation-inhibiting-compound-pri-003/. Accessed November 21, 2024.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/oral-treatment-of-the-sod1g93a-transgenic-mouse-model-of-amyotrophic-lateral-sclerosis-als-with-the-neuro-inflammation-inhibiting-compound-pri-003/