Adenosine modulates many physiological processes by activating specific adenosine receptors. These adenosine receptors play a critical role in the regulation of cellular signaling and are broadly distributed throughout the body. Thus, the ability to modulate adenosine receptor-mediated signaling is an attractive therapeutic strategy for a broad range of diseases. This technology relates to a group of compounds that display high affinity and specificity for the A1 adenosine receptor subtype.

This invention involves ApoA-1 mimetic peptides with multiple amphipathic alpha-helical domains that promote lipid efflux from cells and are useful in the treatment and prevention of dyslipidemic, inflammatory and vascular disorders. IND-enabling studies for one of the peptides, named Fx-5A, are completed in preparation for an IND filing at the FDA, to be followed by a Phase I clinical trial planned for 2017.

The identification of more sensitive and specific markers of atherosclerosis that are non-invasive and cost-effective may have profound impacts on public health. One such strategy involves the detection of marker genes or their products in blood or serum. Such markers may help identify high-risk patients with subclinical atherosclerosis who may benefit from intensive primary prevention or they may help determine the activity of established disease for monitoring response to treatment, resulting in more targeted secondary prevention.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare progressive childhood disorder characterized by premature aging (progeria). Recently, the gene responsible for HGPS was identified (Eriksson M, et al. Nature 2003), and HGPS joined a group of syndromes — the laminopathies — all of which are caused by various mutations in the lamin A/C gene (LMNA). Lamin A is one of the family of proteins that is modified post-translationally by the addition of a farnesyl group.

Prevention of cardiovascular disorders such as myocardial infarction and stroke is an area of major public health importance. Currently, several risk factors for future cardiovascular disorders have been described and are in wide clinical use in the detection of individuals at high risk. However a large number of cardiovascular disorders occur in individuals with apparently low to moderate risk profiles, thereby limiting the ability to identify such patients. Moreover, many of the risk factors require accurate gathering of clinical information.

Exposed collagen in injured blood vessels provides a substrate for platelets to adhere and aggregate initiating the first step in thrombosis, the formation of blood clots inside a blood vessel. Despite the essential role of platelets in vascular injury, excessive platelet aggregation may also result in thrombotic diseases such as stroke and heart attack.

The catalytic subunit of the DNA-dependent protein kinase complex (DNA-PKcs) has been shown to be important in DNA repair and VDJ recombination in lymphocytes. The inventors have discovered that DNA-PKcs also plays novel, important roles in energy regulation and neurological function. The inventors observed that mature DNA-PKcs-deficient mice (also known as SCID mice) have a lower proportion of fat, resist obesity, and have significantly greater physical endurance than wild-type control mice, particularly with increasing age.

Parathyroid hormone receptors found on osteoblasts in bone and renal tubule cells in kidney elevate blood calcium levels when stimulated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Excessive secretion of PTH from the parathyroid gland results in primary hyperparathyroidism. Production of PTHrP by various tumors results in humoral hypercalcemia of malignancy. In both of these conditions, excessive blood calcium levels lead to clinically significant morbidity. A parathyroid hormone antagonist could therefore have therapeutic value.

This invention is directed to use of certain peptide analogs comprising multiple amphipathic helical domains that are able to promote cellular lipid efflux and stimulate lipoprotein lipase activity. As a result, administration of invention peptides lead to reduced incidences of hypertriglyceridemia without inducing toxicity. Existing peptides that stimulate efflux of lipids from cells exhibit unacceptably high toxicity. Invention peptides are superior to existing peptides and can also be used to treat or prevent a vast range of vascular diseases, and their dyslipidemic precursors.

Cryopreservation using liquid nitrogen frozen polyvinyl bags allows for storing cellular materials for extended periods while maintaining their activity and viability. Such bags are commonly used in the clinic to store blood products including blood cells, plasma, hematopoietic stem cells, umbilical cord blood for future uses including transplantation. These materials, typically obtained in limited quantities, may be of great therapeutic value, as is the case of stem cells or cord blood derived cells which can be used to potentially treat a number of diseases.