Methods and compositions for mitochondrial replacement therapy

Abstract

The invention features methods, kits, and compositions for mitochondrial replacement in the treatment of disorders arising from mitochondrial dysfunction. The invention also features methods of diagnosing neuropsychiatric (e.g., bipolar disorder) and neurodegenerative disorders based on mitochondrial structural abnormalities.

What is claimed is: 
     
         1 - 46 . (canceled) 
     
     
         47 . A method of treatment comprising:
 administering to a subject a therapeutic composition comprising human mitochondria isolated from cells and a pharmaceutically acceptable excipient, wherein the mitochondria are in a carrier that is a vesicle or liposome.   
     
     
         48 . The method of  claim 47 , wherein the carrier comprises natural or synthetic lipids. 
     
     
         49 . The method of  claim 47 , wherein the carrier is a vesicle. 
     
     
         50 . The method of  claim 47 , wherein the carrier comprises at least one polypeptide or glycoprotein for generation, viability or targeting of the carrier. 
     
     
         51 . The method of  claim 50 , wherein the at least one polypeptide or glycoprotein is for targeting of the carrier. 
     
     
         52 . The method of  claim 47 , wherein the cells are stem cells, precursor cells, or skeletal muscle cells. 
     
     
         53 . The method of  claim 47 , wherein the cells are neural stem cells, muscle stem cells, satellite cells, liver stem cells, hematopoietic stem cells, bone marrow stromal cells, epidermal stem cells, embryonic stem cells, mesenchymal stem cells, umbilical cord stem cells, precursor cells, muscle precursor cells, myoblast, cardiomyoblast, neural precursor cells, glial precursor cells, neuronal precursor cells, hepatoblasts, neurons, oligodendrocytes, astrocytes, Schwann cells, skeletal muscle cells, cardiomyocytes, or hepatocytes. 
     
     
         54 . The method of  claim 47 , wherein the cells are hematopoietic stem cells, bone marrow stromal cells, mesenchymal stem cells, or umbilical cord stem cells. 
     
     
         55 . The method of  claim 47 , wherein the composition is formulated for systemic delivery. 
     
     
         56 . The method of  claim 47 , wherein the composition is formulated for local delivery. 
     
     
         57 . A method of treatment comprising:
 administering to a subject a therapeutic composition comprising human mitochondria isolated from cells and a pharmaceutically acceptable excipient, wherein the mitochondria are in a carrier that comprises:   (i) a lipid bilayer, a vesicle or, a liposome, and   (ii) at least one polypeptide or glycoprotein.   
     
     
         58 . The method of  claim 57 , wherein the carrier comprises natural or synthetic lipids. 
     
     
         59 . The method of  claim 57 , wherein the polypeptide or glycoprotein is for targeting of the carrier. 
     
     
         60 . The method of  claim 57 , wherein the cells are stem cells, precursor cells, or skeletal muscle cells. 
     
     
         61 . The method of  claim 57 , wherein the cells are hematopoietic stem cells, bone marrow stromal cells, mesenchymal stem cells, or umbilical cord stem cells. 
     
     
         62 . The method of  claim 57 , wherein the composition is formulated for systemic delivery. 
     
     
         63 . The method of  claim 57 , wherein the composition is formulated for local delivery.