This technology includes processes for the synthesis of VBP15 (17a,21-dihydroxy-16a-methyl-pregna-1,4,9(11)-triene-3,20-dione) of high purity and large quantities as a treatment for Duchenne muscular dystrophy. The synthesis of VBP15 has several deficiencies which has hindered larger-scale preparation for clinical evaluation and potential manufacturing. The deficiencies included formation of significant levels of undesired epoxide impurity, formation of undesired ketone impurity, and resultant need for costly chromatographic purification.

This technology includes methods for screening compounds and compositions useful for inhibiting or reducing platelet deposition, adhesion, and/or aggregation. The present invention further relates to methods of treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, abrupt closure following angioplasty or stent placement, thrombosis induced by peripheral vascular surgery, peripheral vascular disease or thrombotic disorders resulting from atrial fibrillation or inflammation.

This technology includes a series of diphenylpropanamides as potent and selective RORgt inhibitors for the treatment of Th17-related autoimmune diseases. The retinoic acid-related orphan receptor RORgt plays an important role in the differentiation of thymocytes, lymphoid tissue inducer cells, and inflammatory T helper-expressing interleukin 17a (Th17) cells. Small molecule RORgt inhibitors may provide means to regulate Th17 mediated immune response.

This technology includes a series of diphenylpropanamides as potent and selective RORgt inhibitors for the treatment of Th17-related autoimmune diseases. The retinoic acid-related orphan receptor RORgt plays an important role in the differentiation of thymocytes, lymphoid tissue inducer cells, and inflammatory T helper-expressing interleukin 17a (Th17) cells. Small molecule RORgt inhibitors may provide means to regulate Th17 mediated immune response.

This technology includes a new class of compounds, called remodelins, which can be used to prevent airway remodeling and prevent lung fibrosis. Currently no effective therapies are available for lung fibrosis. This compound could also be employed as a treatment for asthma.

This technology includes a series of small molecule organic compounds, called remodelins, that are synthetic derivative analogs of a parent compound discovered by screening of a Chembridge library. The novel synthetic derivative analogs were generated through multiple iterations of compounds directed by in vitro experiments. The invention also includes use of these or related molecules to treat cancer and/or glaucoma.

This technology includes novel systemic adeno-associated virus (AAV)-mediated CRISPR gene therapy technology. While some diseases (e.g., retinal diseases) can be treated through local gene transfer, many diseases such as Duchenne Muscular Dystrophy (DMD) require systemic therapy. The CRISPR technology has two components, the Cas9 endonuclease, and the gRNA. To explore systemic CRISPR therapy, we co-delivered the AAV.Cas9 and AAV.gRNA vector to mdx mice, a mouse DMD model. Direct delivery to muscle yielded efficient gene correction.

Aldehyde dehydrogenase enzymes (ALDHs) have a broad spectrum of biological activities through the oxidation of both endogenous and exogenous aldehydes. Unbalanced expression levels of ALDHs have been associated with a variety of disease states such as alcoholic liver disease, Parkinson’s disease, obesity, and multiple types of cancers. ALDH1A1 also plays a major role in preserving the tumor microenvironment via differentiation, self-protection, and proliferation of cancer stem cells.

This technology includes a strategy to generate antibodies of rabbit origin, both polyclonal and monoclonal, which have strong affinity to the TAT sequence and which enable specific immunocapture or immunodetection of TAT containing frataxin and analogs for quantitative or qualitative assays. In addition, antibodies that react with the FXN region have also been generated with this strategy. The HIV virus encoded a translational activator protein containing a 12 amino acid domain which permits transmembrane delivery of any therapeutic protein containing the sequence.

This technology includes the use of JTV-519 and oxidized form of JTV-519, as a novel treatment for Wolfram syndrome and other diseases associated with endoplasmic reticulum (ER). JTV-519 can prevent the leakage of ER calcium to the cytosol and abnormal activation of a pro-apoptotic enzyme, calpain 2, in cell models of Wolfram syndrome. Further, these compounds can prevent cell death in beta cell models of these diseases.