The present invention provides a method of treating NPP1 deficiency or NPP1-associated disease such as idiopathic infantile arterial calcification (IIAC), pseudoxanthoma elasticum, vascular calcification in chronic kidney disease (VCCKD), insulin resistance, hypophosphatemic rickets, myocardial ischemia, joint calcification, angioid streaks, and ossification of the posterior longitudinal ligament of the spine. The present invention provides a method for treating tissue calcification by administering soluble NPP1 to produce a transient increase in serum pyrophosphate levels.

There are provided, inter alia, methods for reacting an enzyme and its substrate, methods for purifying a protein and an enzyme reactor and its use thereof.

The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification by modulating the level or activity of NPP1 or a mutant thereof, or a mutant NPP4 modified to exhibit ATP hydrolase activity similar to the hydrolase activity of NPP1.

A method of synthetizing cyclic oligoadenylates using a novel catalytic activity of a protein possessing the Palm domain, such as the Cas10 protein, and using such compounds for activation of proteins possessing the CARF doman, such as the Csm6 protein.

The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.

The present invention relates to compositions and methods for modulating coagulation through modulating the level or activity of NPP4.

The present invention relates to methods for diagnosing, monitoring or prognosticating prostate cancer or the progression state of prostate cancer wherein said method determines the state of the prostate cancer, based on the expression level of phosphodiesterase 4D (PDE4D) variants. The invention further relates to a method of identifying an individual for eligibility for prostate cancer therapy. The invention also relates to products for the analysis of phosphodiesterase 4D (PDE4D) variants as well as pharmaceutical compositions modulating the activity and/or expression of PDE4D variants.

Compounds, compositions and methods are provided for the inhibition of ENPP1. Aspects of the subject methods include contacting a sample with a cell impermeable ENPP1 inhibitor to inhibit cGAMP hydrolysis activity of ENPP1. Aspects of the methods include administering to a subject in need thereof a therapeutically effective amount of a CAR expressing immune cell in combination with a therapeutically effective amount of a cell impermeable ENPP1 inhibitor to inhibit the hydrolysis of cGAMP.

The present invention provides methods for improving cardiovascular function in a human patient (e.g., reducing hypertension), as well as methods of treating a cardiovascular disease, by administering a recombinant human soluble ectonucleotide pyrophosphatase phosphodiesterase (hsNPP1), active fragment or fusion protein thereof.

The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification by modulating the level or activity of NPP1 or a mutant thereof, or a mutant NPP4 modified to exhibit ATP hydrolase activity similar to the hydrolase activity of NPP1.