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AssigneeUniversity of Virginia Patent Foundation
InventorsSarah Kucenas, Taylor Welsh
Estimating the term…
During development, OPCs migrate extensively throughout the spinal cord, but their migration is restricted at transition zones (TZ). At these specialized locations, unique glial cells in both zebrafish and mice are at least partially responsible for preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. In order to elucidate the signals that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (AR) causes ectopic OPC migration out of the spinal cord. In our studies, we provide in vivo evidence that endogenous neuromodulation by adenosine regulates OPC migration along motor axons, specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease.
A method for stimulating oligodendrocyte progenitor cell (OPC) migration from the spinal cord onto a peripheral motor nerve in a subject, said method comprising administering to the subject a pharmaceutical composition comprising an effective amount of an inhibitor of spinal motor nerve activity.
A method for treating demyelination of a peripheral motor nerve in a subject with a demyelinating disease, disorder, or injury, said method comprising stimulating OPC migration from the spinal cord of said subject to a peripheral motor nerve by administering to the subject a pharmaceutical composition comprising an effective amount of an inhibitor of spinal motor nerve activity, wherein when said OPCs migrate to the peripheral motor nerve said OPCs myelinate said peripheral motor nerve.
20-30. (canceled)
A method for stimulating OPC migration from the spinal cord to a peripheral motor nerve in a subject, said method comprising administering to the subject a pharmaceutical composition comprising an effective amount of a compound selected from the group consisting of 1-OMe-tyrphostin AG 538, L-canavanine sulfate, clofibrate, wortmannin, and an inhibitor of spinal motor nerve activity, wherein said inhibitor is an a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonist or an N-methyl-D-aspartate receptor (NMDAR) antagonist.
32-33. (canceled)
Dependencies are inferred from the claim text.