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 . A therapeutic composition comprising human mitochondria isolated from cells and a pharmaceutically acceptable excipient. 
     
     
         2 . The composition of  claim 1 , wherein the mitochondria are in a carrier. 
     
     
         3 . The composition of  claim 2 , wherein the carrier comprises natural or synthetic lipids. 
     
     
         4 . The composition of  claim 2 , wherein the carrier comprises a lipid bilayer, a vesicle, or a liposome. 
     
     
         5 . A therapeutic composition comprising human mitochondria isolated from cells and a pharmaceutically acceptable excipient, wherein the mitochondria are in a carrier that comprises a lipid bilayer, a vesicle, or a liposome. 
     
     
         6 . The composition of  claim 2 , wherein the carrier further comprises at least one polypeptide or glycoprotein. 
     
     
         7 . The composition of  claim 3 , wherein the carrier further comprises at least one polypeptide or glycoprotein. 
     
     
         8 . The composition of  claim 4 , wherein the carrier further comprises at least one polypeptide or glycoprotein. 
     
     
         9 . The composition of  claim 6 , wherein the polypeptide or glycoprotein is for generation, viability or targeting of the carrier. 
     
     
         10 . The composition of  claim 7 , wherein the polypeptide or glycoprotein is for generation, viability or targeting of the carrier. 
     
     
         11 . The composition of  claim 8 , wherein the polypeptide or glycoprotein is for generation, viability or targeting of the carrier. 
     
     
         12 . The composition of  claim 1 , wherein the cells are stem cells, precursor cells, or skeletal muscle cells. 
     
     
         13 . The composition of  claim 5 , wherein the cells are stem cells, precursor cells, or skeletal muscle cells. 
     
     
         14 . The composition of  claim 1 , 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. 
     
     
         15 . The composition of  claim 5 , 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. 
     
     
         16 . The composition of  claim 1 , wherein the composition is formulated for systemic delivery. 
     
     
         17 . The composition of  claim 1 , wherein the composition is formulated for local delivery. 
     
     
         18 . The composition of  claim 5 , wherein the composition is formulated for systemic delivery. 
     
     
         19 . The composition of  claim 5 , wherein the composition is formulated for local delivery. 
     
     
         20 . A therapeutic composition comprising human mitochondria isolated from cells and a pharmaceutically acceptable excipient, wherein the mitochondria are in a carrier that comprises a lipid bilayer, a vesicle, or a liposome and at least one polypeptide or glycoprotein, and wherein the composition is formulated for systemic or local delivery.