Through both natural evolution of our R&D programs and within our CRO services business, DiscoveryBioMed, Inc. (DBM, Inc.) has identified a sharpening focus in Renal or Kidney Cell Biology and Physiology and in Renal Diseases over the last year, in 2016, and going forward.
We invite interested parties to view our newly redesigned website where this focus is declared and apparent.
It is ironic that DBM’s founder, Dr. Erik Schwiebert, first worked on Renal Cell Physiology while a lab technician, first year Ph.D. student, and Ph.D. candidate while in Dr. Bruce Stanton’s laboratory at Dartmouth. “In my very first memories of culturing rodent and human cells, I was involved in establishing primary cultures and growing those cultures and immortal cell lines from the nephron of the kidney so as to study the regulation of epithelial sodium and chloride channels in collecting duct-derived cells,” Erik explained. “I am very familiar with establishing and growing kidney cells as well as studying them and characterizing them. It is therefore not surprising that DBM has also gravitated to that although it was not overtly intentional.”
DBM’s CRO services business has a new focus in the establishment and use in bioassays of normal and cystic autosomal dominant polycystic kidney disease (ADPKD) renal epithelial cell and fibroblast cultures. Such primary cultures and, eventually, immortalized mixed cultures and clonal immortal cell lines are and will be offered, along with specialty media which has been optimized. Specialty methods are also offered with regard to cell culture and cell-based bioassays.
DBM’s CFTR Ligand R&D program is currently profiling lead small molecules that will be therapeutically valuable in the Renal Diseases umbrella and in multiple, compelling and interesting ways. This ligand will be a single small molecule or ‘monotherapy.’ “Our CFTR Ligands correct delF508-CFTR and potentiate wild-type CFTR but they do so in a way very different to the Vertex corrector drugs. While they do influence CFTR’s anion transport functions therapeutically, they also activate the ‘CFTR signalsome’ robustly. In this light, our CFTR Ligands also cause marked inhibition of ENaC, the epithelial sodium channel, and promote growth arrest or cytostasis in hyperproliferative human cells such as cystic ADPKD cells and fibroblasts and in renal, urologic and other human cancer cell lines,” explains Dr. Schwiebert. It is established that CFTR has the unique property of being an ion transport protein that also anchors a macromolecular signaling complex and influences signal transduction. One can call this CFTR’s conductance regulator function; however, many studies have shown that CFTR influences mucus secretion, immune and inflammatory signaling, and cell growth. Because our CFTR Ligands are “CFTR Signalsome Activators,” these small molecule drugs are being developed as a novel class of anti-proliferative compounds for ADPKD and for cancer. They also have novel utility in cystic fibrosis (CF) and, likely, in other chronic lung diseases such as COPD and asthma. As CFTR signaling activators that inhibit ENaC, this small molecule drug class can also be called a novel class of “CFTR-dependent ENaC Inhibitors,” likely beneficial for treatment of generalized or tissue-specific edema or general or more specific forms of hypertension. Acute inhibitors of ENaC like amiloride and triamterene are now generic and only weak diuretics. For example, one niche form of hypertension is caused by autosomal recessive polycystic kidney disease, a rare form of PKD that afflicts neonates and young children with severe, rapid onset hypertension likely due to up-regulation of ENaC and other sodium transport mechanisms.
DBM’s Adiponectin Secretagogue Ligand R&D programs is currently profiling hit-to-lead small molecules that will be therapeutically valuable in the Renal Diseases umbrella, specifically protection from hyperglycemia-induced diabetic nephropathy. This ligand will be a single small molecule or ‘monotherapy.’ Adiponectin is a beneficial circulating protein secreted by human fat cells or adipocytes into the plasma. This ‘adipokine’ acts as an insulin-sensitizing cofactor because it shares the same target tissues as insulin. And, it is quite abundant in the plasma of normal humans or wild-type animals, where it is protective against injury of fragile tissues (kidney, liver, heart, eye, vasculature) from high blood sugar and high blood fats. Efforts to make a full-length adiponectin protein biologic have proven very difficult and current efforts to engineer adiponectin fragments that can still activate adiponectin receptors have proven challenging. Therefore, DBM sought to discover and develop small molecules that selectively up-regulate the endogenous production and secretion of adiponectin from primary human adipocytes from normal and diseased donors. Current studies in H1 2016 seek to determine if our hit-to-lead compounds stimulate the production and secretion of adiponectin in vivo and to determine whether this causes insulin sensitization and protection from the development of diabetic nephropathy.
Please refer to our new website pages under R&D for our CFTR Ligands program and our Adiponectin Secretagogue Ligands program. If interesting, please inquire to DBM (see contact below) and we can send the latest Top Level and Scientific slide decks for either or both programs.
Contact information: Dr. Erik M. Schwiebert, Ph.D., (205) 918-8138, ext. 1, firstname.lastname@example.org