Targeted Epigenetic Therapy for Inherited Aortic Aneurysm Condition

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Unmet Need
1-2% of all people in industrialized countries die from aortic aneurysms.  A large component have genetically imposed thoracic aortic aneurysm for which transforming growth factor β (TGF-β) is a driver of the disease. A thoracic aortic aneurysm is the "ballooning" of the upper aspect of the aorta, above the diaphragm. Untreated or unrecognized they can be fatal due to dissection or "popping" of the aneurysm leading to nearly instant death.
Perturbations in TGF-β pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems including rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm). One such example includes, Shprintzen-Goldberg syndrome, which is often caused by mutations in the SKI gene that cause perturbations in the TGF-β signaling pathway. Shprintzen-Goldberg syndrome is characterized by vascular issues (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections), skeletal manifestations, craniofacial features, and brain and neurological findings.
Management of Shprintzen-Goldberg syndrome is limited to ameliorate defect symptomologies, surgical correction of skeletal and cardiovascular defects represents the current standard of care for many of these subjects.
Technology Overview
This invention provides methods and compositions for the prevention and treatment of inherited aortic aneurysm conditions by epigenetic modulation.  Johns Hopkins researchers have demonstrated that treatment of mouse models of Shprintzen-Goldberg syndrome with a selective histone acetyltransferase (HAT) inhibitor, normalizes gene expression in the aorta, preserves aortic wall architecture and abrogates aneurysm progression. This strategy is relevant to a broad class of Marfan syndrome related disorders that are associated with altered regulation of TGFb target genes and that may further result in aortic aneurysm.

Stage of Development
Mouse model data available
  • Constitutive or conditional knock-in mouse models of SGS that express a heterozygous missense Ski allele (p.G34D) in all cells or specifically in vascular smooth muscle cells (VSMCs).
Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
Targeted epigenetic therapy for inherited aortic aneurysm condition PRO: Provisional United States 62/553,394 9/1/2017     Expired
Targeted epigenetic therapy for inherited aortic aneurysm condition PCT: Patent Cooperation Treaty PCT PCT/US2018/049217   8/31/2018     Pending
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Nakisha Holder
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