Compositions and methods for modulating blood-brain barrier transport
View Patent ↗This invention provides conjugates of therapeutic or active agents with melanotransferrin or with other ligands of a melanotransferrin receptor, melanotransferrin receptor modulators, and related compositions and methods for modulating blood-brain barrier transport by providing methods of screening and selecting such conjugates, ligands, and modulators in vitro and in vivo, and methods of use of such conjugates, modulators and ligands in diagnosis and the treatment of diseases, including particularly diseases of the central nervous system or lysosomal storage diseases.
1. A method of delivering an active agent across the blood brain barrier in a subject in need thereof comprising administering a composition comprising a conjugate comprising receptor associated protein (RAP) and an active agent.
2. The method of claim 1 wherein the composition further comprises a pharmaceutically acceptable carrier.
3. The method of claim 1 wherein the active agent is a protein.
4. The method of claim 1 wherein the subject is suffering from a neurological cancer selected from the group consisting of a primary brain tumor, glioblastoma, glioma, meningioma, neurinoma, pituitary adenoma, medulloblastoma, craniopharyngioma, hemangioma, epidermoid, sarcoma and intracranial metastasis from other tumor sources.
5. The method of claim 1 wherein the active agent is a chemotherapeutic agent.
6. The method of claim 5 wherein the chemotherapeutic agent is selected from the group consisting of an alkylating agent, an alkaloid, an anti-metabolite, an antibiotic, and an anti-proliferative agent.
7. The method of claim 5 wherein the chemotherapeutic agent is selected from the group consisting of Mechlorethamine hydrochloride, Cyclophosphamide, Ifosfamide, Chlorambucil, Melphalan, Busulfan, Thiotepa (Triethylenethiophosphoramide), Carmustine, Lomustine, Streptozocin, Vincristine, Vinblastine, Paclitaxel, Methotrexate, Mercaptopurine, Thioguanine, Fluorouracil, Cytarabine, Azacitidine, Dactinomycin, Doxorubicin, Daunorubicin, Idarubicin, Bleomycin, Picamycin, Mitomycin, Hydroxyurea, Procarbazine, Dacarbazine, Cisplatin, Carboplatin, Asparaginase, Etoposide, Amsarcrine, Mitotane, and Mitoxantrone.
8. The method of claim 1 wherein the subject is suffering from a neurological disease selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, schizophrenia and epilepsy.
9. The method of claim 1 wherein the active agent is for treating a neurological disorder.