Reducing Myelin-Mediated Inhibition of Axon Regeneration
AssigneeChildren's Medical Center Corporation
InventorsZhigang He, Kevin C. Wang, Vuk Koprivica, Jieun A. Kim
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Abstract
Oligodendrocyte-myelin glycoprotein (OMgp)-specific binding agents are used to reduce OMgp-mediated axon growth inhibition. Mixtures of axons and OMgp and mixtures of Nogo receptor (NgR) and OMgp are used in pharmaceutical screens to characterize agents as inhibiting binding of NgR to OMgp and promoting axon regeneration.
Claims10
A method for reducing axon growth inhibition mediated by OMgp in the central nervous system and detecting resultant reduced axon growth inhibition, the method comprising steps:
- contacting a mixture comprising an axon and OMgp with an exogenous OMgp-specific binding agent and under conditions wherein the agent binds the OMgp and but for the presence of the agent, the axon is subject to growth inhibition mediated by the OMgp, and
- detecting resultant reduced axon growth inhibition, wherein said agent comprises a soluble NgR peptide sufficient to specifically bind the OMgp and competitively inhibit binding of the OMgp to the NgR.
A method for characterizing an agent as inhibiting binding of NgR to OMgp, the method comprising the steps of:
- incubating a mixture comprising NgR, OMgp and an agent under conditions whereby but for the presence of the agent, the NgR and OMgp exhibit a control binding;
- and
- detecting a reduced binding of the NgR to the OMgp, indicating that the agent inhibits binding of the NgR to the OMgp.
A pharmaceutical composition comprising a soluble NgR peptide and a pharmaceutically acceptable excipient, formulated in unit dosage sufficient to specifically bind OMgp and competitively inhibit binding of the OMgp to NgR, wherein the peptide consists of one of SEQ ID NOS:
- 1-6, or truncation thereof at least six residues in length.
Dependencies are inferred from the claim text.