Compositions for the treatment of neuropathic pain and sensitization of tumors to chemotherapies

Abstract

Without limitation, a method for preventing and/or treating neuropathic pain in a subject/patient comprising administering a therapeutically effective amount of exosomes derived and isolated from mammalian cells to the subject/patient and a method of treating cancer in a subject/patient in need thereof, comprises administering a combination comprising a therapeutically effective amount of exosomes derived and isolated from mammalian cells and a chemotherapeutic agent.

1 .- 37 . (canceled) 
     
     
         38 . A pharmaceutical composition comprising exosomes isolated from endothelial cells and a pharmaceutically acceptable excipient, wherein the exosomes comprise exosomal marker proteins Alix and CD63, and endothelial cell protein CD31. 
     
     
         39 . The pharmaceutical composition of  claim 38 , wherein the exosomes are isolated from the group selected from, brain microvascular endothelial cells (BMVECs), Primary Human Brain Microvascular Endothelial Cells, cerebral endothelial cells, endothelial progenitor cells, AG-133/CD-133+ cells, and combinations thereof. 
     
     
         40 . The pharmaceutical composition of  claim 38 , wherein the exosomes are present in the pharmaceutical composition in an amount ranging from 1×10 1  to 1×10 15  exosomes per mL. 
     
     
         41 . The pharmaceutical composition of  claim 38 , wherein the exosomes are derived from human cells. 
     
     
         42 . The pharmaceutical composition of  claim 41 , wherein the exosomes are allogeneic or autologous. 
     
     
         43 . The pharmaceutical composition of  claim 41 , wherein the human cells are human cultured cells. 
     
     
         44 . The pharmaceutical composition of  claim 38 , wherein the exosomes target DRG neurons and sciatic nerve tissue. 
     
     
         45 . The pharmaceutical composition of  claim 38 , wherein the composition further comprises a chemotherapeutic agent. 
     
     
         46 . The pharmaceutical composition of  claim 45 , wherein the chemotherapeutic agent is selected from cytarabine, gludarabine, fluorouracil, mercaptopurine, ixabepilone, arsenic trioxide, etoposide, hexamethylmelamine, ifosfamide, methotrexate, procarbazine, epothilones, bortezomib, lenolidamide thalidomide, thioguanine, gemcitabine, hydroxyurea, vincristine, vinblastine, vinorelbine, topotecan, irinotecan, paclitaxel, docetaxel, asparaginase, busulfan, carmustine, lomustine, chlorambucil, cyclophosphamide, cisplatin, carboplatin, oxaliplatin, ifosamide, mechlorethamine, melphalan, thiotepa, dacarbazine, procarbazine, bleomycin, dactinomycin, daunorubicin, doxorubicin, idarubicin, mitomycin, mitoxantrone, plicamycin, etoposide, teniposide, radiation therapy, and combinations thereof. 
     
     
         47 . The pharmaceutical composition of  claim 45 , wherein the chemotherapeutic agent is ixabepilone, arsenic trioxide, etoposide, hexamethylmelamine, ifosfamide, methotrexate, procarbazine, epothilones, bortezomib, lenolidamide thalidomide, cisplatin, carboplatin, oxaliplatin, vincristine, vinblastine, paclitaxel, and docetaxel, or combinations thereof. 
     
     
         48 . The pharmaceutical composition of  claim 45 , wherein the chemotherapeutic agent is cisplatin, carboplatin, or oxaliplatin. 
     
     
         49 . The pharmaceutical composition of  claim 38 , wherein the pharmaceutical composition is formulated for intravenous (IV), intraperitoneal (IP), intranasal (IN), or subcutaneous (S.C.) administration. 
     
     
         50 . The pharmaceutical composition of  claim 38 , wherein the pharmaceutical composition is effective in preventing or treating neurotoxicity in a subject, wherein the neurotoxicity is associated with a condition selected from: chemotherapy-induced neuropathy, cancer-related neuropathy, HIV-related peripheral neuropathy, post-herpetic neuralgia, diabetic neuropathy, peripheral neuropathy, sciatica, fibromyalgia, chronic fatigue syndrome pain, multiple sclerosis pain, complex regional pain syndrome type I, complex regional pain syndrome type II, central pain syndrome, painful traumatic mononeuropathy, post-surgical pain syndrome, post mastectomy syndrome, post thoracotomy syndrome, phantom pain, nerve root avulsion, post radiation neuropathy, repetitive movement nerve injury, repetitive stress injury, post injury neuropathy, or combinations thereof; in particular in the prevention or treatment of a chemotherapy induced peripheral neuropathy (CIPN). 
     
     
         51 . A method for method of preventing or treating neurotoxicity or cancer in a subject in need thereof, the method comprising administering a pharmaceutical composition comprising a plurality of mammalian exosomes derived from primary or cultured endothelial cells, wherein the mammalian exosomes express Alix, CD31, and CD63. 
     
     
         52 . The method according to  claim 51 , wherein the neurotoxicity is a neurotoxicity induced by radiation, cancer, drug therapies, or organ transplants. 
     
     
         53 . The method according to  claim 51 , wherein the neurotoxicity causes sensory and motor dysfunction, abnormal sensitivity, vascular dysfunction, limb weakness, loss of vision, loss of memory or intellect, headache, behavioral problems, sexual dysfunction, motor dysfunction, organ and gland dysfunction, hearing loss, allodynia, pain, numbness, tingling, burning, dizziness, muscle wasting or weakness, peripheral neuropathy or paralysis. 
     
     
         54 . The method according to  claim 51 , wherein the mammalian exosomes are autologous or allogeneic. 
     
     
         55 . The method according to  claim 51 , wherein the method of treating cancer further comprises administering a chemotherapeutic agent. 
     
     
         56 . A method for treating cancer in a subject in need thereof, the method comprises administering a therapeutically effective composition comprising mammalian exosomes derived from one or more endothelial cells, wherein the mammalian exosomes express Alix, CD31, and CD63 and the composition sensitizes the cancer to the treatment of a chemotherapeutic agent; wherein the chemotherapeutic agent is a platinum chemotherapeutic agent. 
     
     
         57 . The method according to  claim 56 , wherein the platinum chemotherapeutic agent is oxaliplatin. 
     
     
         58 . The method according to  claim 56 , wherein the mammalian exosomes are derived from primary or cultured cerebral endothelial cells.