Uridine diphosphate compounds as mobilizers of hematopoietic progenitor cells

Abstract

The present invention provides for compositions and methods for administering one or more UDP compound, alone or in combination with another hematopoietic progenitor cell mobillizing compound (for example, but not limited to, G-CSF), to mobilize hematopoietic progenitor cells for transplant or other purposes. The methods of the invention may be particularly advantageous as applied to improve the stem cell yield in so-called “poor mobilizing” patients.

We claim: 
     
         1 . A pharmaceutical composition comprising a uridine diphosphate (UDP) compound and a second hematopoietic cell mobilizing compound. 
     
     
         2 . A pharmaceutical composition comprising a uridine diphosphate (UDP) compound and a second hematopoietic cell mobilizing compound, in an amount effective to mobilize hematopoietic stem cells from the bone into peripheral circulation of a subject in need thereof. 
     
     
         3 . The pharmaceutical composition of  claim 1 , where the UDP compound is UDP-glucose. 
     
     
         4 . The pharmaceutical composition of  claim 1 , where the UDP compound is UDP. 
     
     
         5 . The pharmaceutical composition of  claim 1 , where the UDP compound is selected from the group consisting of UDP-galactose, UDP-N-acetylglucosamine, UDP-glucuronic acid, 5′-O-[[[[(2″,3″,4″,6″-tetra-O-benzoyl-α-D-glucopyranosy)oxy]carbonyl]amino]sulfonyl]uridine (P536), UDP-6S-6C-methylglucose, UDP-6R-6C-methylglucose, Diphosphoric acid 1-α-D-glucopyranosyl ester 2-[(4′-methylthio)uridin-5″-yl] ester disodium salt (MRS 2690), a mixture of one or more of the aforelisted compounds with UDP glucose or UDP, and a mixture of two or more of the foregoing. 
     
     
         6 . The pharmaceutical composition of  claim 1 , where the second hematopoietic cell mobilizing compound is granulocyte colony stimulating factor. 
     
     
         7 . The pharmaceutical composition of  claim 1 , where the second hematopoietic cell mobilizing compound is selected from the group consisting of poly-(1,6)-β-D-glucopyranosyl-(1,3)-β-D glucopyranose (PGG) β-glucan, 1,1′-[1,4-phenylenebis(methylene)]bis [1,4,8,11-tetraazacyclotetradecane] (AMD3100), cyclophosphamide, fucoidan, and a mixture thereof. 
     
     
         8 . The pharmaceutical composition of  claim 1 , where the subject in need thereof is going to have radiation therapy or chemotherapy. 
     
     
         9 . The pharmaceutical composition of  claim 1 , where the subject in need thereof has received chemotherapy. 
     
     
         10 . The pharmaceutical composition of  claim 1 , where the subject in need thereof is being prepared to donate hematopoietic stem progenitor cells. 
     
     
         11 . The pharmaceutical composition of  claim 1 , where the subject in need thereof has been exposed to a toxic level of radiation. 
     
     
         12 . The pharmaceutical composition of  claim 1 , where the subject in need thereof suffers from long term bone marrow failure (BMF) or Fanconi's anemia (FA).