# US 2024/0197789 A1 · Treatment of canavan disease > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2024/0197789 A1 - Document ID: US20240197789A1 - Status: Published application - Kind: A1 - Application number: 18/488,859 - Filed: 2023-10-17 - Published: 2024-06-20 - Earliest claimed: 2016-06-22 - Assignees: City of Hope - Applicants: City of Hope - Inventors: Yanhong SHI; Jianfei CHAO; Wendong LI - Web page: https://patentgrep.com/patent/US20240197789A1 ## CPC - A61K 35/30: Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue - A61P 25/00: Drugs for disorders of the nervous system - C12N 5/0623: {Stem cells} - C12N 5/0696: {Artificially induced pluripotent stem cells, e.g. iPS} - A01K 2217/075: inducing loss of function, i.e. knock out - A01K 2227/105: Murine - A01K 2267/0318: Animal model for neurodegenerative disease, e.g. non- Alzheimer's - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C12N 2501/602: Sox-2 - C12N 2501/603: Oct-3/4 - C12N 2501/604: Klf-4 - C12N 2501/606: c-Myc - C12N 2501/608: Lin28 - C12N 2506/1307: from adult fibroblasts - C12N 2506/45: from artificially induced pluripotent stem cells - C12N 2510/00: Genetically modified cells - C12N 2740/16043: viral genome or elements thereof as genetic vector - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS ## Abstract Disclosed herein are methods of treating Canavan disease in a subject through restoring ASPA enzymatic activities in the subject by expressing exogenous wild type ASPA gene in the brain of the subject. Also disclosed are a process of producing neural precursor cells, including NPCs, glial progenitor cells and oligodendroglial progenitor cells, which express an exogenous wild type ASPA gene and the neural precursor cells produced by this process. ## Claims ### Claim 1 A method for treating Canavan disease in a subject, comprising: reprogramming or converting somatic cells isolated from the subject into induced pluripotent stem cells (iPSCs); obtaining ASPA neural progenitor cells (NPCs) expressing wild type or functional ASPA; wherein at least 90% of the ASPA NPCs are CD133 positive and SSEA4 negative; and transplanting the ASPA NPCs into the brain of the subject, wherein the ASPA NPCs are obtained by: differentiating the iPSCs into NPCs and introducing wild type ASPA gene into the NPCs by (i) transducing the NPCs with a lentivirus vector comprising the wild type ASPA gene, or (ii) correcting mutated ASPA gene of the NPCs by CRISPR/Cas 9 or TALEN-based gene editing. ### Claim 2 (depends on 1) The method of claim 1, wherein the reprogramming is carried out in the presence of one or more reprogramming factors comprising OCT4, SOX2, KLF4, LIN28 and MYC. ### Claim 3 (canceled) ### Claim 4 (depends on 1) The method of claim 1, wherein the ASPA gene of the reprogrammed iPSCs comprises one or more mutations. ### Claim 5 (depends on 4) The method of claim 4, wherein the ASPA gene mutation is a heterozygous mutation. ### Claim 6 (depends on 4) The method of claim 4, wherein the ASPA gene mutation is a homozygous mutation. ### Claim 7 (depends on 4) The method of claim 4, wherein the ASPA gene mutation is 527G>A, 914C>A, or 854A>C. ### Claim 8 (depends on 1) The method of claim 1, wherein the somatic cells are fibroblasts, blood cells, urinary cells, adipocytes, keratinocytes, or dental pulp cells. ### Claim at position 9 9-13. (canceled) ### Claim 14 A method of producing ASPA neural precursor cells, comprising: reprogramming or converting somatic cells isolated from a subject suffering from Canavan disease into induced pluripotent stem cells (iPSCs); and obtaining ASPA neural precursor cells expressing wild type or functional ASPA by conducting a genetical correction of the iPSCs before or after differentiating the iPSCs into the neural precursor cells, wherein the ASPA neural precursor cells are obtained by: introducing wild type or functional ASPA gene in the iPSCs to obtain genetically corrected iPSCs which express wild type or functional ASPA, wherein at least 90% of the ASPA NPCs are CD133 positive and SSEA4 negative; and differentiating the genetically corrected iPSCs into neural precursor cells or differentiating the iPSCs into neural precursor cells; and introducing wild type or function ASPA gene into the neural precursor cells. ### Claim 15 (depends on 14) The method of claim 14, wherein the reprogramming is carried out, in the presence of one or more reprogramming factors comprising OCT4, SOX2, KLF4, LIN28 and MYC. ### Claim 16 (depends on 14) The method of claim 14, wherein the reprogramming is carried out via episomal reprogramming or viral transduction. ### Claim 17 (depends on 14) The method of claim 14, wherein the somatic cells are fibroblasts, blood cells, urinary cells, adipocytes, keratinocytes, dental pulp cells, or other easily accessible somatic cells. ### Claim 18 (depends on 14) The method of claim 14, wherein the wild type or functional ASPA gene is introduced by transducing the reprogrammed or converted iPSCs with a vector comprising the wild type or functional ASPA gene or by correcting the ASPA gene mutation using gene editing technology. ### Claim 19 (depends on 18) The method of claim 18, wherein the vector is lentivirus. ### Claim 20 (depends on 14) The method of claim 14, wherein the neural precursor cells include NPCs, glial progenitor cells and oligodendroglial progenitor cells. ### Claim at position 17 21-27. (canceled) ### Claim 28 (depends on 1) The method of claim 1, wherein the NPCs are differentiated into oligodendrocyte progenitor cells (OPCs) and oligodendrocytes. ### Claim 29 A method for treating Canavan disease in a subject, comprising: (a) the population comprising NPCs that are: (i) derived from differentiated iPSCs that are in turn derived from reprogrammed or converted somatic cells isolated from the subject, and (ii) genetically corrected to express a wild type or functional ASPA gene by: transducing the NPCs with a lentivirus vector comprising the wild type or functional ASPA gene, or correcting mutated ASPA gene of the NPCs by CRISPR/Cas 9 or TALEN-based gene editing; (iii) at least 90% CD133 positive and SSEA4 negative; and (b) transplanting, into the brain of the subject, the population of ASPA NPCs. ### Claim 30 (depends on 29) The method of claim 29, wherein the somatic cells are fibroblasts, blood cells, urinary cells, adipocytes, keratinocytes, or dental pulp cells.