Pharmaceuticals & Biologics
Nogo-B is a newly-discovered protein that is highly expressed in endothelial and smooth muscle cells of the vessel wall. Nogo-B has been shown to be a regulator of cell migration in vitro and of vascular remodeling in vivo. Molecules that mimic the activity of Nogo-B have been shown to be pro-angiogenic. More recently, the receptor for Nogo-B has been identified. Antagonists of the receptor have been shown to be anti-angiogenic, and therefore useful for the treatment of solid tumors. Work at Yale is underway to identify additional anti-angiogenic molecules.
This invention demonstrates that blocking the Transforming Growth Factor β (TGF-β) pathway in peripheral innate immune cells such as macrophages significantly clears up b-amyloid plaques/reduces brain Ab levels and improves other aspects of Alzheimer’s-like pathology including astrogliosis and behavioral impairment.
Few remedies exist to slow the ravages of old age such as Parkinsons, Alzheimer's, and osteoporosis. The lin-4 microRNA represses a molecule in the insulin signaling pathway, a pathway known to regulate lifespan in nematodes, flies and mice. Delivering this microRNA to humans will slow the effects of aging and assist in treating diseases of old age. MicroRNAs are natural human chemicals and hence microRNA treatments utilize a natural pathway which are likely to be more effective than other approaches.
Yale researchers have developed biodegradable polymeric microparticles containing one or more active agents for the sustained delivery of ophthalmic drugs. Drugs include latanaprost for glaucoma, and triamcinolone for diabetic retinopathy and uveitis. Drug release has been shown over several months.
Glaucoma is the second leading cause of blindness in the world, and the risk for developing the disease increases with age. It is associated with a rise in intraocular pressure (IOP), the reduction of which can usually preserve vision. While effective IOP-lowering medications are available, they require continuous administration, up to several times per day in some cases. Non-compliance with glaucoma medications is very high among elderly patients, with frequent administration requirements strongly associated with nonadherence. This novel treatment addresses the large and growing compliance issue with a sustained delivery timolol maleate injection. With the possibility of administration once every few months at routine doctor's visits, daily compliance is negated.
Yale researchers have identified, expressed, purified, and crystallized to ultra-high resolution a novel therapeutic domain of a vascular resident protein that can normalize clotting in the serum of patients with platelet granule disorders.
The invention includes methods of preventing and reversing prefrontal cortical decline in normal aged subjects by providing a protein kinase C inhibitor to the subject. The protein kinase C inhibitor can be a phenanthridinium alkaloids or other closely related compound. The inventors have found that when such compounds are administered to normal aged subjects the cognitive performance, including including performance in tasks that utilizing working memory, of the subjects improves.
Yale scientists have discovered that the level of IL-18 and its downstream targets were increased in patients with COPD, as well as in the lungs of smokers. Furthermore, it was found that treating mice with antibody against IL-18Rα significantly decreased Cigarette Smoke (CS) - induced inflammation. IL-18 signaling contributes to the pathogenesis of CS-induced emphysema, pulmonary inflammation and apoptosis. Therefore, the levels of circulating IL-18 represent a readily accessible biomarker for the diagnosis of COPD, and blocking IL-18Rα would be an effective therapy against COPD.
Methods for increasing the patency of biodegradable, synthetic vascular grafts are provided. The methods include administering one or more cytokines and/or chemokines that promote outward tissue remodeling of the vascular grafts and vascular neotissue formation. The disclosed methods do not require cell seeding of the vascular grafts, thus avoiding many problems associated with cell seeding. Biodegradable, polymeric vascular grafts which provide controlled release of cytokines and/or chemokines at the site of vascular graft implantation are also provided.
The recent discovery of a role for SEMA 7A in fibrosis using mouse models provides a new therapeutic target for the treatment of fibrosis in lung disease and may be suitable for the treatment of other fibrotic diseases.