Epigenetic Therapy for Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is the most common of hereditary cardiac conditions and is related to mutations in sarcomere proteins, the most frequent of which is MYBPC (cardiac myosin protein C). While MYPB-C mutations are associated with HCM, there is a marked heterogeneity in phenotypic responses to mutations of this gene, even within families, and this could be explained by epigenetic factors such as hypermethylation. UCD researchers have shown that the DNA methylation inhibitor 5-azacitidine (5-aza) improves cardiac function, including hypertrophy and diastology, in a murine animal model (SHR, spontaneously hypertensive rat, model) and this is associated with up-regulation of MYBP-C, and more surprisingly actin alpha1 skeletal muscle (ACTA1), gene expression in cardiomyocytes. Therefore, DNA methylation inhibitors may represent a novel therapeutic strategy for the prevention and treatment of HCM, in particular the Orphan indications HOCM and FHCM. 5-aza is a hypomethylation agent that could be repurposed for Orphan indications in HCM.
Microfluidic Cell Culture Platform for Cell Based Assays
UCD researchers have developed a microfluidic cell culture platform for cell-based assays that simultaneously exposes cells to multiple linear concentration gradients formed in different directions. Diffusion-based, stable gradients can be formed within one hour and can be maintained for days without inducing shear stresses on the cells. The platform is suitable for medium throughput screening with brightfield or fluorescence visualization/quantitation of cells via microscopic imaging or a plate reader. Combinatorial drug screening and dose optimization studies can be performed, where equal numbers of cells are exposed to combinations of each compound at defined concentrations. Other potential applications include cell migration, live-cell tracking and post-fixation immunocytochemistry.
Novel Topical Therapeutic for Retinal Vascular Disease
UCD has developed novel, small molecule, anti-angiogenic compounds to offer patients and clinicians cost-effective, easily administered, safe and sustainable therapeutics to prevent blindness from retinal vascular diseases. The retinal therapeutics market is estimated at $3 billion (2012); it is a high growth market with significant unmet need. The dramatic entry of Lucentis (anti-VEGF antibody intravitreal drug) into the market in 2007 and the success of anti-angiogenic drugs have highlighted the opportunity for products in the retinal disease market. The entry of topical or slow release preparations into the market would eliminate the current practice of repeated intravitreal injections and the associated safety risks and clinical burden. In addition, there is a cohort of patients unresponsive to current treatments, underscoring the need for new therapeutics.
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