NOTCH3 agonist compositions and methods for treating small vessel diseases
View Patent ↗The present subject matter provides, inter alia compositions, formulations, and methods for inhibiting, treating, and preventing small vessel diseases.
1. A method for treating a small vessel disease (SVD) in a subject, comprising administering to the subject an effective amount of a Neurogenic Locus Notch Homolog Protein 3 (NOTCH3) agonist, wherein the NOTCH3 agonist comprises a polypeptide comprising a JAGGED1 extracellular domain or fragment thereof that comprises a stretch of amino acids having the sequence set forth in SEQ ID NO: 1.
2. The method of claim 1 , wherein
the polypeptide comprises a stretch of amino acids having the sequence or set forth in SEQ ID NO:2.
3. The method of claim 1 , wherein the subject has diabetic retinopathy, age-related macular degeneration (AMD), nephropathy, microangiopathy, heart failure, Alagille syndrome, familial tetralogy of Fallot, patent ductus arteriosus, or a cerebral cavernous malformation.
4. The method of claim 1 , wherein the NOTCH3 agonist is administered as a monotherapy.
5. The method of claim 1 , wherein the subject has a loss-of-function mutation in NOTCH3.
6. The method of claim 1 , wherein the SVD is cerebral SVD.
7. The method of claim 6 , wherein the cerebral SVD is cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) or cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).
8. The method of claim 6 , wherein the cerebral SVD is cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
9. The method of claim 6 , wherein the cerebral SVD is cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).