Compositions and methods for the treatment of lysosomal storage disorders

• US 9,700,601 B2
• Filed: 10/28/2013
• Issued: 07/11/2017
• Est. Priority Date: 12/04/2003
• Status: Active Grant

• Current Assignee: Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Regents of The University of Minnesota (University of Minnesota)
• Inventors: Tolar, Jakub, Verfaillie, Catherine M., Blazer, Bruce
• Primary Examiner(s): Lankford, Blaine
• Application Number:
  US14/064,517
• Publication Number:
  US 20140212393A1
• Time in Patent Office: 1,352 Days
• Field of Search: None
• CPC Class Codes: A61K 35/48 Reproductive organs
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 5/0607 Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696

Abstract

The present invention relates to methods for providing lysosomal enzymes to a subject by administering stem cells, preferably Multipotent Adult Progenitor Cells (MAPCs). The invention further relates to methods for treating lysosomal storage disorders by administering stem cells.

Claims

1. A method for treating a lysosomal storage disorder comprising administering stem cells to a subject having a lysosomal storage disorder, wherein the stem cells are isolated expanded human non-embryonic stem, non-germ cells, that express telomerase, have undergone about 10-40 doublings in culture, and can differentiate into cell types of at least two of the endodermal, ectodermal, and mesodermal lineages, and wherein the stem cells naturally express an amount of lysosomal enzyme effective to treat said disorder, wherein the non-embryonic non-germ non-embryonic germ cells are derived from bone marrow.

2. The method of claim 1, wherein the lysosomal storage disorder is selected from the group consisting of sphingolipidoses, mucopolysaccharidoses, glycoproteinoses, mucolipidoses, glycogenosis type II and ceroid lipofuscinoses.

3. The method of claim 1, wherein the lysosomal storage disorder is selected from the group consisting of GM1 gangliosidosis, GM2 gangliosidosis variant B/B1 and variant O, metachromatic leukodystrophy, Krabbe'"'"'s disease, Fabry'"'"'s disease, Gaucher'"'"'s disease, Niemann-Pick disease, Farber'"'"'s disease, Wolman'"'"'s disease, Austin'"'"'s disease, mucopolysaccharidoses type I, Scheie'"'"'s disease, Hurler-Scheie'"'"'s disease, Sanfilippo'"'"'s disease, Morquio'"'"'s disease, Maroteaux-Lamy'"'"'s disease, Sly'"'"'s disease, pycnodysostosis, aspartylglucosaminuria, fucosidosis, α

-mannosidosis, β

-mannosidosis, Schindler'"'"'s disease, Kanzaki'"'"'s disease, mucolipidoses type I, galactosialidosis, mucolipidoses, glycogenosis type II, Santavuori-Haltia disease, Jansky-Bielshowsky disease, Batten disease, Kufs disease, disease states characterized by mutations in the CLN5, CLN6, CLN7 and CLN8 loci, sialic acid storage diseases, Salla disease, and methylmalonic aciduria.

4. The method of claim 2, wherein the subject has mucopolysaccharidosis.

5. The method of claim 4, wherein the mucopolysaccharidosis is Hurler'"'"'s disease.

6. The method of any of claims 1-5, wherein the non-embryonic, non-germ cells express one or more of oct4, rex-1, and rox-1.

7. The method of claim 1, wherein the stem cells are administered by a method selected from the group consisting of localized injection, catheter administration, systemic injection, intraperitoneal injection, intraplacental injection, intrauterine injection, intracranial injection, parenteral administration, intraarterial injection and injection into the lateral cerebral ventricles.