Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases
Inventors
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Vascular BioSciencesVascular Biosciences (VBS) is an innovative biomedical company developing breakthrough solutions to critical military and civilian medical challenges including: Military Infectious Diseases, Sepsis, Combat Casualty Care, Acute High Altitude Pulmonary Edema, and CBRN medical countermeasures. Our inflammation homing peptide, CARSKNKDC (CAR), enables increased localized concentrations of drugs to dramatically improve therapeutic outcomes with reduced side-effects. CAR converts systemically administered drugs into precision medicines. CAR peptide, by itself, also dramatically speeds up wound healing.
Vascular Biosciences (VBS) is an innovative biomedical company developing breakthrough solutions to critical military and civilian medical challenges including: Military Infectious Diseases, Sepsis, Combat Casualty Care, Acute High Altitude Pulmonary Edema, and CBRN medical countermeasures. Our inflammation homing peptide, CARSKNKDC (CAR), enables increased localized concentrations of drugs to dramatically improve therapeutic outcomes with reduced side-effects. CAR converts systemically administered drugs into precision medicines. CAR peptide, by itself, also dramatically speeds up wound healing.
Publication Number
US-8741861-B2
Publication Date
2014-06-03
Expiration Date
Abstract
The present invention discloses multiple treatment regimens for vascular-related diseases and disorders. The present invention provides for methods of treating vascular-related disorders based on gene expression studies from samples collected from individuals having symptoms of vascular-related disorders. Additionally, methods are disclosed involving diagnostic techniques to focus treatment regimens. Finally, methods of treating vascular-related disorder involving targeting microRNAs are also disclosed.
Core Innovation
The invention provides a gene-expression-guided treatment strategy for an individual suffering from the vascular-related disease pulmonary arterial hypertension. It obtains a biopsy sample from the individual's pulmonary artery and analyzes gene expression levels in comparison with a non-diseased control, including genes chosen from the group consisting of HSPE, YES1, CFTR, MAOA, MAOB, and CACNA2D1. At least one gene is identified as upregulated or downregulated in the biopsy sample based on the non-diseased control.
The method obtains gene products from the identified genes and selects pharmaceutical agents based on the direction of dysregulation. Pharmaceutical agents are selected as known inhibitors of the gene products from the at least one upregulated gene and as known promoters of the gene products from the at least one downregulated gene, and the selected pharmaceutical agents are administered to the individual suffering from pulmonary arterial hypertension.
The document also describes catheter-based endoarterial biopsy for serial acquisition of pulmonary arterial samples and gene-expression profiling using mRNA microarray and microRNA expression profiling to characterize time- and stage-dependent dysregulation. It reports concordant dysregulated genes with known pulmonary arterial hypertension pathways and novel dysregulated genes previously unassociated with the disease, together with pressure/flow-stage-dependent microRNA changes.
Claims Coverage
The provided material includes one independent claim. This independent claim covers the full pipeline from obtaining a pulmonary artery biopsy and comparing gene expression to a non-diseased control, through selecting inhibitors or promoters of gene products for administration to an individual with pulmonary arterial hypertension. The dependents refine biopsy sampling, gene-expression measurement, and early-stage treatment with table-listed drugs.
Pulmonary artery biopsy-guided gene expression comparison to non-diseased control
Obtaining a biopsy sample from the individual's pulmonary artery; analyzing gene expression levels of the biopsy sample and the non-diseased control for genes chosen from the group consisting of HSPE, YES1, CFTR, MAOA, MAOB, and CACNA2D1; comparing gene expression levels between the biopsy sample and the non-diseased control; and identifying at least one gene upregulated or downregulated based on the non-diseased control.
Direction-specific selection of pharmaceutical agents from gene products
Obtaining gene products from the genes identified as upregulated or downregulated, selecting pharmaceutical agents that are known inhibitors of the gene products from the at least one upregulated gene or known promoters of the gene products from the at least one downregulated gene, and administering the selected pharmaceutical agents to the individual.
Endoarterial catheter extraction of the pulmonary artery biopsy
Carrying out obtaining a biopsy sample such that the biopsy sample is extracted using an endoarterial catheter.
RNA-based gene expression analysis and comparison via cDNA
Analyzing gene expression levels by extracting RNA from the biopsy sample and converting RNA into cDNA for use in the comparison step.
Microarray-based gene expression analyzing
Performing the analyzing of gene expression levels using a microarray.
Early-stage progression treatment using table-listed drugs
Treating early-stage progression of a vascular-related disease using at least one pharmaceutical agent selected from the group consisting of the drugs listed in Table 3.
Overall, the claim coverage centers on biopsy-sample gene expression comparison to a non-diseased control to identify upregulated and downregulated genes from a defined set, followed by selecting direction-specific inhibitors or promoters of the corresponding gene products for administration to treat pulmonary arterial hypertension. Dependent claims refine the biopsy extraction and gene-expression workflow and constrain early-stage treatment to table-listed drugs.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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