Use of thiazolide compounds for the prevention and treatment of viral diseases, cancer and diseases caused by intracellular infections

Abstract

The invention provides for the use of pharmaceutical compositions comprising a thiazolide in the stimulation of the immune system in a subject in need thereof, thereby preventing and/or treating viral diseases, cancer and diseases caused by intracellular protozoan infections

1 . A method of stimulating an immune response in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a thiazolide compound, wherein the thiazolide compound is nitazoxanide or tizoxanide or RM-4848, or a salt, polymorph, ester, amide, prodrug, or derivative thereof. 
     
     
         2 . The method of  claim 1 , wherein the subject suffers from or is at risk of developing a viral infection, a cancer or an intracellular protozoan infection. 
     
     
         3 . The method of  claim 1 , wherein the thiazolide compound is administered in combination with a vaccine. 
     
     
         4 . The method of  claim 1 , wherein the thiazolide compound is administered in combination with an immunostimulant. 
     
     
         5 . The method of  claim 4 , wherein the immunostimulant is Imiquimod or Resiquimod. 
     
     
         6 . The method of  claim 1 , wherein the thiazolide compound is administered in combination with a neuraminidase inhibitor, selected from the group consisting of Laninamivir, Oseltamivir, Zanamivir and Peramivir. 
     
     
         7 . The method of  claim 1 , wherein the thiazolide compound is administered in combination with an adamantine analogue. 
     
     
         8 . The method of  claim 1 , wherein the thiazolide compound is administered in combination with a recombinant sialidase fusion protein. 
     
     
         9 . The method of  claim 1 , wherein stimulating the immune response results in treatment or prevention of a viral infection in the subject. 
     
     
         10 . The method of  claim 9 , wherein the viral infection is influenza infection. 
     
     
         11 . The method of  claim 10 , wherein the viral infection is caused by a virus selected from H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7N3, and H10N7. 
     
     
         12 . The method of  claim 9 , wherein the viral infection is Hepatitis B. 
     
     
         13 . The method of  claim 9 , wherein the thiazolide compound is administered in combination with an anti-hepatitis B drug. 
     
     
         14 . The method of  claim 9 , wherein the thiazolide compound is administered in combination with a vaccine. 
     
     
         15 . The method of  claim 9 , wherein the thiazolide compound is administered in combination with an immunostimulant. 
     
     
         16 . The method of  claim 15 , wherein the immunostimulant is Imiquimod or Resiquimod. 
     
     
         17 . The method of  claim 9 , wherein the thiazolide compound is administered in combination with an adamantine analogue. 
     
     
         18 . The method of  claim 9 , wherein the thiazolide compound is administered in combination with a recombinant sialidase fusion protein. 
     
     
         19 . The method of  claim 1 , wherein stimulating the immune response results in treatment or prevention of a cancer in the subject. 
     
     
         20 . The method of  claim 19 , wherein the cancer is leukemia. 
     
     
         21 . The method of  claim 20 , wherein the leukemia is hairy cell leukemia or chronic myeloid leukemia. 
     
     
         22 . The method of  claim 19 , wherein the cancer is melanoma. 
     
     
         23 . The method of  claim 19 , wherein the cancer is non-Hodgkin lymphoma. 
     
     
         24 . The method of  claim 19 , wherein the cancer is renal cell carcinoma. 
     
     
         25 . The method of  claim 19 , wherein the thiazolide compound is administered in combination with a vaccine. 
     
     
         26 . The method of  claim 19 , wherein the thiazolide compound is administered in combination with an immunostimulant. 
     
     
         27 . The method of  claim 19 , wherein the thiazolide compound is administered in combination with an anticancer drug. 
     
     
         28 . The method of  claim 27 , wherein the anticancer drug is selected from the group consisting of STI571, CGP 74588, 1-β-D-Arabinofuranosylcytosine (Ara-C), doxorbicin, dacarbazine, cisplatin, bleomycin, vincristine, lomustine, vinblastine, carmustine, DTIC, tamoxifen, sunitinib, sorafenib and interferon-α. 
     
     
         29 . The method of  claim 1 , wherein stimulating the immune response results in treatment or prevention of an intracellular protozoan infection in the subject. 
     
     
         30 . The method of  claim 29 , wherein the intracellular protozoan infection is selected from the group consisting of  Cryptosporidium  spp.,  Leishmania  spp.,  Toxoplasma gondii  and  Trypanosoma cruzii.    
     
     
         31 . The method of  claim 29 , wherein the thiazolide compound is administered in combination with a vaccine, or an immunostimulant, or an antiprotozoal drug. 
     
     
         32 . The method of  claim 31 , wherein the thiazolide compound is administered in combination with an antiprotozoal drug selected from the group consisting of trimethoprim/sulfamethoxazole, atovaquone, clindamycin, pyrimethamine, spiramycin, diminazine, homidium, suramin, melarsamine, sodium stibogluconate and meglumine antimoniate. 
     
     
         33 . The method of  claim 29 , wherein stimulating the immune response results in treatment or prevention of an intracellular bacterial infection. 
     
     
         34 . The method of  claim 33 , wherein the intracellular bacterial infection is  Mycobacterium tuberculosis.