The present disclosure provides methods and compositions useful for the treatment or prevention of heart disease. In particular, the present disclosure provides a vector comprising a modified troponin promoter operatively linked to a therapeutic gene product for the treatment or prevention of heart disease, e.g., cardiomyopathy. The gene product may be MYBPC3. The disclosure also provides recombinant adeno-associated virus (rAAV) virions, rAAV viral genomes, and expression cassettes and pharmaceutical compositions thereof. The disclosure further provides methods for treating a disease or disorder, such as heart disease.

A pharmaceutical composition can be provide for treating or preventing heart failure. Additionally, siRNA and a vector expressing said siRNA can be provided that can be used in the pharmaceutical composition for treating or preventing heart failure. For example, a pharmaceutical composition can be provided for treating or preventing heart failure that contains a DNA sequence encoding RNA containing a sense strand sequence of consecutive 18 to 29 nucleotides from angiopoietin-like protein 2 (ANGPTL2) mRNA or the alternative splicing type RNA thereof and an antisense strand sequence complementary to the sense strand sequence under control of a promoter, and a pharmaceutically acceptable carrier.

The present invention relates to the identification of a microRNA family, designated miR-29a-c, that is a key regulator of fibrosis in cardiac tissue. The inventors show that members of the miR-29 family are down-regulated in the heart tissue in response to stress, and are up-regulated in heart tissue of mice that are resistant to both stress and fibrosis. Also provided are methods of modulating expression and activity of the miR-29 family of miRNAs as a treatment for fibrotic disease, including cardiac hypertrophy, skeletal muscle fibrosis other fibrosis related diseases and collagen loss-related disease.

Disease model pigs produced by nuclear transplantation, disease model pigs exhibiting stable phenotypes and production methods thereof are provided. Chimeric pigs for producing disease model pigs exhibiting stable phenotypes, genital glands thereof, and germ cells thereof are also provided. A method for producing a genetically modified disease model pig, includes: (a) transplanting a nucleus of a genetically modified cell into cytoplasm of an egg; (b) developing an obtained clonal embryo in a womb of a female pig to obtain an offspring; and mating the obtained offspring or having the offspring undergo sexual reproduction to further obtain the genetically modified offspring as a disease model pig.

A method for preventing or treating atherosclerosis or atherosclerosis-related diseases in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of sDSS1 protein or a fragment or variant thereof, a nucleic acid encoding the sDSS1 protein or a fragment or variant thereof or a vector containing the nucleic acid, transplanting into the individual with a cell expressing the sDSS1 protein or a fragment or variant thereof, or tissues or organs containing the sDSS1 protein or a fragment or variant thereof or the nucleic acid, and/or infusing into the individual serum or interstitial fluid containing the sDSS1 protein or a fragment or variant thereof or the nucleic acid.

The present disclosure provides compositions and methods for treating, preventing, or inhibiting laminopathies. In one aspect, the disclosure provides nucleic acid constructs and/or vectors comprising a nucleotide sequence encoding lamin A and/or lamin C.

Provided herein is a gene therapy for PKP2 (Plakophilin-2), e.g. using an adeno-associated virus (AAV) vector. The promoter of the vector may be a MHCK7 promoter or a cardiac troponin T (HTNNT2) promoter. The capsid may be an AAV9 or AAVrh74 capsid or a functional variant thereof. Other promoters or capsids may be used. Further provided are methods of treatment, such as by intravenous, intracoronary, intracarotid or intracardiac administration of the rAAV vector, and other compositions and methods.

The present disclosure provides methods and compositions useful for the treatment or prevention of heart disease. In particular, the present disclosure provides a vector comprising a modified troponin T promoter operatively linked to a therapeutic gene product for the treatment or prevention of heart disease, e.g., cardiomyopathy. The gene product may be MYBPC3. The disclosure also provides recombinant adeno-associated virus (rAAV) virions, rAAV viral genomes, and expression cassettes and pharmaceutical compositions thereof. The disclosure further provides methods for treating a disease or disorder, such as heart disease.

[Problem] The objectives of the present invention are to provide a method for making an animal that has been stressed, in particular, chronically stressed, affect or develop a specific disease or symptom, and, through elucidating the process from loading stress to affection or onset of the disease or symptom, to provide a useful tool for research and development of preventing or treating methods of the disease or symptom. [Solution] The present invention relates to a method for producing a disease modeling non-human animal having cerebrovascular inflammation, the disease modeling non-human animal, a method for screening a drug using the disease modeling non-human animal, a method for determining the risk of a disease using the presence of cerebrovascular inflammation as an indicator, and a pharmaceutical for preventing and/or treating progressive multiple sclerosis or the like. The present invention enables developing pharmaceuticals for the above described diseases or the like and performing researches for elucidating their pathogenic mechanisms. The present invention also enables determining the risk of affection or onset of progressive multiple sclerosis or the like and preventing and/or treating progressive multiple sclerosis or the like.

The invention is in the field of molecular diagnosis of medical diseases and their treatment. More in particular, it provides methods and means for detecting hypertension, more in particular essential primary hypertension, even more in particular NOX5-dependent hypertension. The invention also provides methods for the treatment of hypertension, in particular essential primary hypertension, more in particular NOX5-dependent hypertension. The invention also provides theragnostics, wherein therapy is combined with diagnosis, more in particular wherein the level of NOX5 is determined in a sample from a subject and wherein the subject is treated with NOX5 inhibitors or compounds that decrease the levels of NOX5 if the NOX5 levels are above a certain threshold value. Further, the invention also provides theragnostics, wherein diagnosis is combined with therapy, more in particular wherein the (plasma) level of NOX5 is determined in a sample from a subject and wherein the subject is treated with NOX5 inhibitors or compounds that reverse the result of NOX5 activity in the subject, when the determined NOX5 level is exceeding a predetermined threshold level. Finally, the invention relates to an animal model suitable for developing diagnostic methods and therapeutic treatments for NOX5-dependent hypertension.