Modified Flavonoids as Selective Inhibitors of Hylauronidases for the Promotion of Remyelination
Abstract
Inflammatory demyelination is a hallmark of multiple sclerosis (MS). Identifying safe and efficacious strategies that promote functional remyelination remains an unmet need. Our published and preliminary data support a model of remyelination failure where the activity of a type of enzyme, called a hyaluronidase, within demyelinating lesions generates chemical messengers that prevent remyelination. Our preliminary data also indicate that modified flavonoids, chemical compounds with structures similar to natural products from certain plants, can potently inhibit hyaluronidase activity, and that at least one can promote remyelination in mice. Based on these findings, we hypothesize that specific modification to flavonoids will result in highly potent and selective inhibition of hyaluronidase activity in demyelinating lesions and will promote functional remyelination. Demyelination is a significant cause of debilitation in patients with all forms of MS. Loss of myelin leads to conduction deficits or even conduction block in affected axons, contributing to motor, sensory, and cognitive dysfunction. If successful, the studies outlined in this proposal will demonstrate the potential of modified flavonoids to promote remyelination and limit demyelination and will provide the rationale for further evaluating specific compounds in preclinical and clinical trials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710101
Entities
People
- Lawrence Sherman
Organizations
- Oregon Health & Science University
- United States Army