Treatment of cerebrovascular disease with neurogenic locus notch homolog protein 3 (NOTCH3) agents
The present disclosure provides methods of treating subjects having a cerebrovascular disease by administering Neurogenic Locus Notch Homolog Protein 3 (NOTCH3) agents, and methods of identifying subjects having an increased risk of developing a cerebrovascular disease.
1 . A method of treating a subject having a subcortical stroke, an ischemic stroke, a hemorrhagic stroke, or a parenchymal stroke, the method comprising administering a Neurogenic Locus Notch Homolog Protein 3 (NOTCH3) agent to the subject, wherein the NOTCH3 agent comprises an inhibitory nucleic acid molecule, a small interfering RNA (siRNA), or a short hairpin RNA (shRNA) that hybridizes to a NOTCH3 nucleic acid molecule, and wherein the subject is heterozygous or homozygous for a NOTCH3 missense variant nucleic acid molecule encoding NOTCH3 Arg1231Cys, and wherein the subject has no family history of stroke.
2 . A method of treating a subject having a subcortical stroke, an ischemic stroke, a hemorrhagic stroke, or a parenchymal stroke, the method comprising:
detecting the presence or absence of a NOTCH3 missense variant nucleic acid molecule encoding a NOTCH3 predicted gain-of-function polypeptide in a biological sample obtained from the subject; and
administering a Neurogenic Locus Notch Homolog Protein 3 (NOTCH3) agent to the subject, wherein the NOTCH3 agent comprises an inhibitory nucleic acid molecule, a small interfering RNA (siRNA), or a short hairpin RNA (shRNA) that hybridizes to a NOTCH3 nucleic acid molecule,
wherein the subject is heterozygous or homozygous for a NOTCH3 missense variant nucleic acid molecule encoding NOTCH3 Arg1231Cys, and wherein the subject has no family history of stroke.