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Published on: September 12, 2016
Significant Suppression of Multiple Sclerosis in the Mouse EAE Model Using the PrC-210 Aminothiol
William E Fahl1,2, Bryan L Fahl1,2, Sarah R Goesch1
1Obvia Pharmaceuticals Ltd., Mountain View, CA 94043, USA.
Abstract:
Multiple sclerosis (MS) is a complex disease marked by chronic neuroinflammation and reactive oxygen species (ROS) toxicity in the central nervous system (CNS). Based on this ROS-driven mechanism, we tested whether PrC-210-a new aminothiol ROS scavenger-could lessen MS symptoms in mice with experimental autoimmune encephalomyelitis (EAE)-induced MS. Our goals were to assess the role of ROS in MS and evaluate the potential benefits of PrC-210 for managing MS. Mice with EAE received varying doses of PrC-210 under preventive and therapeutic protocols. Disease progression was measured using clinical scores and spinal cord histology. Safety was assessed by comparing the gastrointestinal and hematological toxicity between PrC-210 and dimethyl fumarate (DMF, Tecfidera's active agent). PrC-210 reduced MS severity by up to 62% in paralysis scores versus those in the controls (p = 0.0001), whether used preventively or at the onset of paralysis. The group with the greatest decrease also showed the best spinal cord preservation and least demyelination. DMF caused toxicity at a dose that was ineffective, while PrC-210 showed no toxicity at effective levels. These findings suggest that the systemic administration of PrC-210 may offer a safe, effective MS treatment when started at symptom onset.
Insights
A novel compound, PrC-210, effectively reduced multiple sclerosis (MS) symptoms and spinal cord damage in mice. This promising agent demonstrated safety and efficacy, offering potential for new MS treatments.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple sclerosis (MS) is characterized by neuroinflammation and reactive oxygen species (ROS) toxicity in the central nervous system (CNS).
- Understanding the role of ROS in MS pathogenesis is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of ROS in MS using a mouse model of experimental autoimmune encephalomyelitis (EAE).
- To evaluate the efficacy and safety of PrC-210, a novel aminothiol ROS scavenger, as a potential MS treatment.
Main Methods:
- EAE mice were treated with varying doses of PrC-210 under preventive and therapeutic regimens.
- Disease progression was monitored using clinical scores and spinal cord histology.
- Safety was assessed by comparing gastrointestinal and hematological toxicity with dimethyl fumarate (DMF).
Main Results:
- PrC-210 significantly reduced MS severity, with up to a 62% decrease in paralysis scores (p = 0.0001).
- Effective treatment with PrC-210 correlated with improved spinal cord preservation and reduced demyelination.
- PrC-210 demonstrated a favorable safety profile, showing no toxicity at effective doses, unlike DMF.
Conclusions:
- Systemic administration of PrC-210 shows potential as a safe and effective treatment for MS.
- PrC-210 may be particularly beneficial when initiated at the onset of MS symptoms.
- Targeting ROS with scavengers like PrC-210 represents a promising therapeutic strategy for MS.
