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US 2026/0183326 A1Published application
Increasing klotho levels
AssigneeAdvantage Therapeutics, Inc.
InventorsCi-Di Chen, Carmela Abraham, Menachem Abraham
Life of this patent
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Abstract
The present disclosure relates to compositions and methods for increasing the level of Klotho in a cell or in a subject and in particular to compositions and methods for treating diseases or conditions associated with Klotho. The methods described herein involve supplementing the level of Klotho protein in a cell by administering to the cell a nucleic acid encoding the Klotho protein.
Claims20
1:
- A method of supplementing a cell with a Klotho protein the method comprising administering to the cell a ribonucleic acid (RNA) encoding the Klotho protein such that the RNA is expressed within the cell to produce the Klotho protein.
2:
- A method of treating a Klotho-related disease or condition in a subject the method comprising administering to the subject a therapeutically effective amount of a ribonucleic acid (RNA) encoding a Klotho protein such that the RNA is expressed within a cell of the subject to produce the Klotho protein.
3:
- The method of claim 1 or claim 2 wherein the cell is a liver cell, a kidney cell, a brain cell or a muscle cell.
4:
- The method of claim 2 wherein the disease or condition is a kidney disease, a liver disease, a cardiovascular disease or a muscle disease.
5:
- The method of claim 2 wherein the disease or condition is acute kidney injury or chronic kidney disease.
6:
- The method of claim 2 wherein the disease or condition is cancer, Duchenne muscular dystrophy, Alzheimer's disease, cognitive impairment, multiple sclerosis, Parkinson's disease or amyotrophic lateral sclerosis.
7:
- The method of claim 2 wherein the disease or condition is pancreatic cancer.
(canceled)
9:
- The method of claim 1 or claim 2 wherein the RNA is administered in a lipid nanoparticle.
10:
- The method of claim 9 wherein the lipid nanoparticle comprises an ionizable cationic lipid, DOPE, cholesterol and DMG-PEG.
11:
- The method of claim 2 wherein the RNA is administered intravenously, intramuscularly, intranasally or intraperitoneally.
12:
- The method of claim 2 wherein the RNA is administered at least once per week for at least 2 weeks.
13:
- The method of claim 2 wherein the RNA is administered at least twice per week for at least 2 weeks.
14:
- The method of claim 1 or claim 2 wherein the RNA encodes a transmembrane isoform of Klotho (m-KL) between about 130 kDa and 140 kDa.
15:
- The method of claim 1 or claim 2 wherein the RNA encodes a soluble KL1+KL2 isoform of Klotho between about 125 kDa and 135 kDa.
16:
- The method of claim 1 or claim 2 wherein the RNA encodes a secreted isoform of Klotho (s-KL) between about 65 kDa and 75 kDa.
17:
- The method of claim 1 or claim 2 wherein the RNA encodes a KL1 isoform of Klotho between about 65 kDa and 75 kDa.
18:
- The method of claim 1 or claim 2 wherein the Klotho is a KL-VS variant.
19:
- The method of claim 1 or claim 2 wherein the RNA does not integrate into the genome of the cell.
20:
- The method of claim 1 or claim 2 wherein the RNA is administered in combination with an agent that increases endogenous Klotho expression.
Dependencies are inferred from the claim text.