Methods of using geldanamycin and FK506 to treat peripheral nerve damage
AssigneeOregon Health & Science University
InventorBruce G. Gold
Life of this patent
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Abstract
FK506 and geldanamycin promote nerve regeneration by a common mechanism that involves the binding of these compounds to polypeptide components of steroid receptor complexes other than the steroid hormone binding portion of the complex (FKBPS52 and hsp90, respectively). These and other agents cause hsp90 dissociation from steroid receptor complexes or block association of hsp90 with steroid receptor complexes.
Claims34
A method of promoting nerve growth a mammal having a partially transected peripheral nerve, the method comprising:
- administering to the mammal a pharmaceutical composition comprising a nerve growth stimulating amount of a non-FKBP12-binding agent that binds to a polypeptide component of a steroid receptor complex other than a steroid hormone binding portion of the complex wherein the agent interferes with association or promotes dissociation of hsp90 with the complex and promotes nerve growth;
- and
- grafting to the peripheral nerve an allograft or an artificial nerve graft, thereby promoting nerve growth in the mammal.
A method of treating a mammal having partially transected peripheral nerve, comprising identifying a compound that stimulates nerve cell growth, by determining whether the agent promotes disruption or interferes with assembly of a steroid receptor complex, and applying the compound locally to the partially transected nerve, thereby treating the mammal.
A method of promoting nerve repair in a mammal having a peripheral nerve injury, the method comprising:
- administering to the mammal a pharmaceutical composition comprising a nerve repair stimulating amount of an agent, other than FK506, that binds to a polypeptide component of a steroid receptor complex other than a steroid hormone binding portion of the complex, and which promotes hsp90 dissociation or inhibits hsp90 association with the complex, and promotes repair of the injury, wherein the peripheral nerve injury is a partial transection.
A method of improving nerve growth into a partial transection of a peripheral nerve, comprising:
- introducing into the transection NGF and a non-cellular gap filling agent that includes a therapeutically effective amount of a benzoquinone ansamycin that binds to a polypeptide component of a steroid receptor complex other than a steroid binding portion of the complex, wherein the NGF and benzoquinone ansamycin are present in a therapeutically sufficient amount to interfere with association or promote dissociation of hsp90 from the complex, and promote nerve growth into the transection.
Dependencies are inferred from the claim text.