VX-765 Reduces Disease Progression in Preclinical Model of Multiple Sclerosis

VX-765 Reduces Disease Progression in Preclinical Model of Multiple Sclerosis

Posted by Valerie Walters on Oct 26, 2020 5:00 am

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system that disrupts the flow of information within the brain and between the brain and body. MS involves an immune-mediated process in which an abnormal response of the body’s immune system is directed against the central nervous system. Damage to areas of the central nervous system may produce a variety of neurological symptoms that will vary among people with MS in type and severity. The progress, severity, and specific symptoms of MS in any one person cannot yet be predicted. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. The cause of MS is still unknown. Scientists believe that a combination of environmental and genetic factors contribute to the risk of developing MS.

According to a recent study, intranasal administration of an anti-inflammatory drug helped reduce disease progression in a preclinical model of MS. Christopher Power, a professor in the Faculty of Medicine & Dentistry, and Leina Saito, a graduate student on his team, showed that delivering an anti-inflammatory drug to mice helped prevent damage to brain cells, effectively slowing the progression of the disease. Power’s research group is particularly interested in inflammasomes, molecules that are responsible for the activation of an inflammatory response in the body. For a disease such as MS, that response must be controlled to halt the progression. Power's lab identified a drug called VX-765 as a strong candidate therapy for MS patients.

VX-765, also known as Belnacasan, is a pharmaceutical compound that acts as a potent and selective inhibitor of the enzyme caspase 1. In previous preclinical trials, VX-765 was efficiently converted to VRT-043198 when administered orally to mice and inhibited LPS-induced cytokine secretion. The result was a blocking of IL-1beta and IL-18 secretion, without much effect on the release of several other cytokines, including IL-1{alpha}, tumor necrosis factor-{alpha}, IL-6, and IL-8. There was also no demonstrable activity in cellular models of apoptosis, and it did not affect the proliferation of activated primary T-cells or T-cell lines. VX-765 has been shown to reduce disease severity and the expression of inflammatory mediators in models of rheumatoid arthritis and skin inflammation, suggesting that it may be useful for the treatment of

 

Chemical structure of VX 765

 

 

In previous research, Power's group saw beneficial results by delivering insulin intranasally in other models of brain inflammation, and he decided to go with that delivery route again. Using mouse models, Power dissolved VX-765 in a fluid and then injected the mixture into the nose. "The study shows intranasal therapy is effective in preventing demyelination and axon injury and loss, so that's a real tonic for us to keep going," said Power. "The loss of myelin and loss of nerves are irreversible processes, so any therapy that helps to slow or prevent that from happening is an exciting advance for MS research. The particular delivery method also allows the therapy to be delivered in a more precise and targeted way."

List of VX-765 and related compounds currently available:

Compounds More details
Belnacasan (VX-765) https://www.vulcanchem.com/product/inhibitors/VC1098039
VRT-043198 https://www.vulcanchem.com/product/inhibitors/VC1096399
Emricasan https://www.vulcanchem.com/product/inhibitors/VC1096391
Nivocasan https://www.vulcanchem.com/product/inhibitors/VC1098061
Pralnacasan https://www.vulcanchem.com/product/inhibitors/VC1080215

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