Compositions and methods for diagnosing, treating, and preventing lysosomal storage diseases
AssigneeWylder Nation Foundation
InventorsMaria Dolores LEDESMA, Edward H. SCHUCHMAN, Angel GAUDIOSO
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Abstract
The present disclosure provides compositions and methods of identifying, making, and using the same for the prevention and treatment of lysosomal storage diseases. Provided are also compositions and methods of diagnosing lysosomal storage diseases.
Claims66
A method of determining an increased risk of a lysosomal storage disease in a subject, the method comprising determining an increased level of sphingomyelin in the subject as compared to a baseline level of the subject or an otherwise comparable healthy subject.
A method of preventing or treating a lysosomal storage disease, the method comprising administering an agent in an amount effective to reduce a level of sphingomyelin in the brain of a subject in need thereof, wherein the agent targets a metabolic enzyme that comprises a ceramide synthase.
A composition comprising:
- a) an inhibitor of a ceramide synthase;
- b) a short hairpin RNA (shRNA) targeting a ceramide synthase;
- c) a guide RNA that targets a nucleic acid sequence encoding a ceramide synthase;
- or
- d) a guide RNA that targets a ribonucleic acid sequence encoding acid sphingomyelinase.
An AAV particle comprising a sequence encoding a short hairpin RNA (shRNA) targeting a ceramide synthase.
An AAV particle comprising a sequence encoding a short hairpin RNA (shRNA) targeting a ceramide synthase, wherein the shRNA targets a sequence that is bound by or complementary to at least one of SEQ ID NO:
- 23 or SEQ ID NO:
- 25.
A method of determining whether an agent is neuromodulatory, the method comprising determining a blood plasma concentration of sphingomyelin in a subject treated with an agent, wherein a decrease in the blood plasma concentration as compared to a baseline level is indicative of the efficacy of the compound as a neuromodulatory agent.
A method of selecting a biomarker, the method comprising:
- administering a composition comprising ASM to a subject;
- and
- detecting a level of a lipid in the subject after the administering, wherein when the level of the lipid decreases in a liver of the subject but not a brain or plasma, the lipid is selected.
A composition comprising m/z805.
Dependencies are inferred from the claim text.