Compositions, methods and uses for alpha-1 antitrypsin or derivatives thereof

Abstract

Embodiments herein report methods and compositions for treating or preventing adverse effects of radiation therapies. In certain embodiments, compositions and methods relate to reducing or inhibiting damage due to acute, periodic or chronic radiation exposure.

1 . A method for ameliorating adverse effects of graft-versus-host disease in a subject comprising, administering to a subject undergoing or scheduled to undergo a transplant or transfusion a therapeutically effective amount of a composition comprising alpha-1 antitrypsin (AAT), a fragment thereof or a mutant thereof wherein the composition modulates the adverse effects of the transplant or transfusion in the subject. 
     
     
         2 . The method of  claim 1 , wherein the composition comprises naturally occurring AAT (SEQ ID NO:1 or SEQ ID NO:39). 
     
     
         3 . The method of  claim 1 , wherein the composition comprises a composition of one or more carboxyterminal fragments of naturally occurring AAT. 
     
     
         4 . The method of  claim 1 , wherein the subject is undergoing a transplant or transfusion for a condition. 
     
     
         5 . The method of  claim 4 , wherein the condition is cancer. 
     
     
         6 .- 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the composition is administered in a therapeutically effective amount to reduce or prevent at least one transplant-induced effect selected from the group consisting of myelosuppression, renal toxicity, weight loss, behavioral changes, pain, nausea, vomiting, diarrhea, constipation, anemia, malnutrition, hair loss, numbness, changes in tastes, loss of appetite, thinned or brittle hair, mouth sores, memory loss, hemorrhage, cardiotoxicity, hepatotoxicity, ototoxicity, and or a combination thereof. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the subject is a human subject. 
     
     
         11 . The method of  claim 1 , wherein the composition is administered to the subject in an amount effective to reduce or prevent cellular damage induced by the transplant or transfusion. 
     
     
         12 . The method of  claim 1 , wherein the therapeutically effective amount of the composition comprises a single intravenous infusion in the subject of AAT at a dose of 1 mg/kg to 150 mg/kg, optionally followed by additional treatments with the composition. 
     
     
         13 . The method of  claim 1 , wherein the therapeutically effective amount of the composition comprises a concentration of AAT of 1 mg/kg to about 150 mg/kg, before, during or after the transplant or transfusion. 
     
     
         14 . The method of  claim 1 , wherein the therapeutically effective amount of the composition comprises a concentration of AAT of 1 mg/kg to about 100 mg/kg administered to the subject every 24 to 48 hours after the transplant or transfusion up to a predetermined time period. 
     
     
         15 . The method of  claim 1 , wherein the administration comprises at least two doses of AAT from about 40 to 80 mg/kg every 24 to 48 hours for a period of from 2 days to 30 days after the transplant or transfusion. 
     
     
         16 . The method of  claim 1 , wherein the transplant or transfusion comprises allogeneic hematopoietic stem cell transplantation. 
     
     
         17 .- 19 . (canceled) 
     
     
         20 . A method for ameliorating adverse effects of a transfusion comprising, administering to a subject having been exposed to the transfusion a therapeutically effective amount of a composition comprising alpha-1 antitrypsin (AAT), a fragment thereof, a recombinant molecule thereof or a mutant thereof wherein the composition modulates the adverse effects of the transfusion in the subject. 
     
     
         21 .- 27 . (canceled) 
     
     
         28 . The method of  claim 4 , wherein the condition is a lymphohematopoietic disorder. 
     
     
         29 . The method of  claim 28 , wherein the lymphohematopoietic disorder is leukemia.