Biosimilars for the treatment of infectious diseases: the case of biosimilar interferons.

Biopharmaceuticals are the fastest-growing and the most expensive among prescription drugs. A biopharmaceutical drug can cost a patient between USD 25,000 and USD 120,000 a year. Such sophisticated medicines are critical options for many unmet medical needs where no sufficient therapies are available, and the demand for lower-cost biopharmaceuticals is tremendous. Biosimilars are similar to, but not the same as, innovative biopharmaceuticals. Since they are developed following patent expiration of innovative medicines, biosimilars represent a potentially lower-cost option to patients and healthcare providers. With a broad range of biopharmaceuticals going off patent, the biosimilars field became the focus of attention of drug developers, healthcare providers, patient advocate groups and politicians. Regulatory and marketing issues for biosimilars have been discussed in several recent reviews. The main focus of this article is the scientific spects of interferon-α biosimilars and next-generation interferons for the treatment of hepatitis C.

Peptidomic profiling of human cerebrospinal fluid identifies YPRPIHPA as a novel substrate for prolylcarboxypeptidase.

Prolylcarboxypeptidase (PRCP) is a serine protease that catalyzes the cleavage of C-terminal amino acids linked to proline in peptides. It is ubiquitously expressed and is involved in regulating blood pressure, proliferation, inflammation, angiogenesis, and weight maintenance. To identify the candidate proximal target engagement markers for PRCP inhibition in the central nervous system, we profiled the peptidome of human cerebrospinal fluid to look for PRCP substrates using a MS-based in vitro substrate profiling assay. These experiments identified a single peptide, with the sequence YPRPIHPA, as a novel substrate for PRCP in human cerebrospinal fluid. The peptide YPRPIHPA is from the extracellular portion of human endothelin B receptor-like protein 2.

Adipose fibroblast growth factor 21 is up-regulated by peroxisome proliferator-activated receptor gamma and altered metabolic states.

Adipose tissue is a metabolically responsive endocrine organ that secretes a myriad of adipokines. Antidiabetic drugs such as peroxisome proliferator-activated receptor (PPAR) gamma agonists target adipose tissue gene expression and correct hyperglycemia via whole-body insulin sensitization. The mechanism by which altered gene expression in adipose tissue affects liver and muscle insulin sensitivity (and thus glucose homeostasis) is not fully understood. One possible mechanism involves the alteration in adipokine secretion, in particular the up-regulation of secreted factors that increase whole-body insulin sensitivity. Here, we report the use of transcriptional profiling to identify genes encoding for secreted proteins the expression of which is regulated by PPARgamma agonists. Of the 379 genes robustly regulated by two structurally distinct PPARgamma agonists in the epididymal white adipose tissue (EWAT) of db/db mice, 33 encoded for known secreted proteins, one of which was FGF21. Although FGF21 was recently reported to be up-regulated in cultured adipocytes by PPARgamma agonists and in liver by PPARalpha agonists and induction of ketotic states, we demonstrate that the protein is transcriptionally up-regulated in adipose tissue in vivo by PPARgamma agonist treatment and under a variety of physiological conditions, including fasting and high fat diet feeding. In addition, we found that circulating levels of FGF21 protein were increased upon treatment with PPARgamma agonists and under ketogenic states. These results suggest a role for FGF21 in mediating the antidiabetic activities of PPARgamma agonists.