Mitochondrial augmentation therapy of renal diseases
AssigneeMinovia Therapeutics Ltd.
InventorsNatalie Yivgi Ohana, Uriel Halavee, Shmuel Bukshpan, Moriya Blumkin, Noa Sher
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Abstract
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating renal diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
Claims27
-3. (canceled)
The method of claim 28, wherein the exogenous mitochondria are syngeneic or allogeneic.
-6. (canceled)
The method of claim 28, wherein the disease or disorder is selected from the group consisting of nephropathy, nephritis, nephrosis, nephritic syndrome, nephrotic syndrome, Fanconi's syndrome and kidney failure.
The method of claim 28, wherein the symptom is selected from the group consisting of low blood alkaline phosphatase levels, low blood magnesium levels, high blood creatinine levels, low blood bicarbonate levels, low blood base excess levels, high urine glucose/creatinine ratios, high urine chloride/creatinine ratios, high urine sodium/creatinine ratios, high blood lactate levels, high urine magnesium/creatinine ratios, high urine potassium/creatinine ratios, high urine calcium/creatinine ratios and high blood urea levels.
-12. (canceled)
The method of claim 28, wherein the mitochondrially-enriched human stem cells have at least one of:
- an increased mitochondrial DNA content;
- (ii) an increased level of citrate synthase (CS) activity;
- (iii) an increased content of at least one mitochondrial protein selected from SDHA and COX1;
- (iv) an increased rate of 02 consumption;
- (v) an increased rate of ATP production;
- or
- (vi) any combination thereof, relative to the corresponding level in the stem cells prior to mitochondrial enrichment.
-16. (canceled)
The method of claim 28, wherein the human stem cells are hematopoietic stem cells, mesenchymal stem cells, pluripotent stem cells (PSCs), induced pluripotent stem cells (iPSCs), or CD34+ cells.
-21. (canceled)
The method of claim 28, wherein the human stem cells are isolated, derived or obtained from cells of the bone marrow, adipose tissue, oral mucosa, skin fibroblasts, blood or umbilical cord blood.
The method of claim 28, wherein the human exogenous mitochondria are isolated or obtained from placenta, placental cells grown in culture or blood cells.
(canceled)
The method of claim 28, wherein the human exogenous mitochondria constitute at least 1-30% of the total mitochondria in the mitochondrially enriched human stem cells.
The method of claim 28, wherein the composition further comprises non-enriched stem cells, megakaryocytes, erythrocytes, mast cells, myeloblasts, basophils, neutrophils, eosinophils, monocytes, macrophages, natural killer (NK) cells, small lymphocytes, T lymphocytes, B lymphocytes, plasma cells, reticular cells, or any combination thereof.
A method of treating a renal disease, disorder or a symptom thereof in a human patient in need of such treatment comprising administering parenterally a pharmaceutical composition to the patient, the pharmaceutical composition comprising at least about 5×105 to 5×109 human stem cells, wherein the human stem cells are enriched with human exogenous mitochondria, and wherein the renal disease or disorder is not a primary mitochondrial disease or disorder caused by a pathogenic mutation in mitochondrial DNA or by a pathogenic mutation in nuclear DNA encoding a mitochondrial protein.
Dependencies are inferred from the claim text.