Pharmacological inhibition of complement C5a-C5a₁ receptor signalling ameliorates disease pathology in the hSOD1^G93A mouse model of amyotrophic lateral sclerosis.

ABSTRACT:

Background and purpose

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing motor neuron disease without effective treatment. The complement system is up-regulated in ALS, with recent studies indicating that the activation product C5a accelerates disease progression via the C5a₁ receptor (C5aR1). We therefore examined the therapeutic effect of C5a₁ receptor antagonism in hSOD1^G93A mice, the most widely used preclinical model of ALS.

Experimental approach

The selective and orally active C5a₁ receptor antagonist, PMX205, was administered to hSOD1^G93A mice in drinking water, both pre- and post-disease onset. Blood, brain and spinal cord pharmacokinetics were performed using LC-MS/MS methods. Effects of PMX

SUBMITTER: Lee JD 

PROVIDER: S-EPMC5368046 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature