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Archive - Mar 17, 2015

Clues to New Microfluidic Systems and More Powerful Glues Come from the Velvet Worm

The velvet worm is a slow-moving, unassuming creature. With its soft body, probing antennae, and stubby legs, it looks like a slug on stilts as it creeps along damp logs in tropical climates. But it has a secret weapon. In the dark of night, when an unsuspecting cricket or termite crosses its path, the worm unleashes an instantaneous torrent of slime. Two fine jets of the gluey substance spray out of openings on its head, oscillating in all directions to cast a sticky net that entraps prey and stops it in its tracks. Captivated, so to speak, by the worm’s split-second attack, researchers from Harvard School of Engineering and Applied Sciences (SEAS) and from universities in Chile, Costa Rica, and Brazil have been studying the creature from all angles. How, they asked, does such a slow, neurologically simple worm execute such a rapid and perfectly aimed movement? By applying new insights from anatomy, mathematics, experimental physics, and fluid dynamics, they now have an answer—published online on March 17, 2015 in an open-access article in Nature Communications—and the findings could inspire new microfluidic devices. Imagine a large syringe equipped, at its narrow tip, with an elastic tube shaped like the neck of a bendy drinking straw. That is apparently the velvet worm’s slime-shooting apparatus, from its tail end—where the slime is produced and stored in a reservoir—to a pair of tiny nozzles called papillae on its head. Given this structure, a slow and gentle squeeze on the reservoir is all it takes to eject the slime with great speed and force. Most importantly, the shape and elasticity of the papillae ensure that as the slime exits, it sprays in all directions, like water gushing through a flailing garden hose. “The geometry of the system allows the worm to squirt fast and cover a wide area.

Zon Zones in on Gilead’s Miracle Hepatitis C Drug (Solvaldi™)

In his latest “Zone in with Zon” blog post blog, dated March 16, 2015, and published by TriLink BioTechnologies of San Diego, Dr. Gerald Zon declares that Gilead’s new drug Solvaldi™ for treatment of hepatitis C virus (HCV) infections is “truly a drug developer’s dream come true.” And Dr. Zon should certainly know, having been intimately involved in drug discovery and development for many years. He notes that the Gilead’s nucleotide-analog prodrug is reported to produce an over 90% cure rate in HCV-infected patients over a 12-week (84-day) course of treatment that involves simply taking one pill per day. That, Dr. Zon says, is “amazing.” However, he immediately remarks that this powerful benefit comes at a considerable expense, with a single Solvaldi pill costing $1,000 and a full-treatment cost of $84,000 per patient. He adds that the estimated manufacturing cost of manufacturing per pill is $68-$138 and this huge disparity between the cost and the price being charged has been the subject of considerable controversy. Particular concerns have been raised as to how this pricing will influence the impact of this drug in developing countries where HCV infection is relatively high, and also in U.S. prison populations where HCV infection is rampant. Before addressing these and other ticklish issues, Dr. Zon provides some useful history on the development of this “miracle drug.” Apparently, it all began with work by two companies, Pharmasset, which was founded on the East Coast in 1998, and Gilead Sciences, Inc., which was founded on the West Coast in 1987. Pharmasset did significant early R&D work on development of an oral drug for HCV treatment and this work ultimately allowed the company to go public in 2007. Dr.

Stem Cell Method Uses Sangamo Zinc-Finger Nucleases to Correct Sickle Cell Disease Mutation

UCLA stem cell researchers have shown that a novel stem cell gene therapy method could one day provide a one-time, lasting treatment for the most common inherited blood disorder in the United States – sickle cell disease. Published online on March 2, 2015 in the journal Blood, the study outlines a method that corrects the mutated gene that causes sickle cell disease and shows, for the first time, that the gene correction method leads to the production of normal red blood cells. The study was directed by renowned stem cell researcher and UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member, Dr. Donald Kohn. The article is titled “Correction of the Sickle-Cell Disease Mutation in Human Hematopoietic Stem/Progenitor Cells.” People with sickle cell disease are born with a mutation in their beta-globin gene, which codes for part of the tetrameric protein that forms hemoglobin the protein responsible for delivering oxygen to the body through blood circulation. Typically, hemoglobin is made of two alpha chains and two beta chains. Sickle cell disease is an autosomal recessive disease, meaning that affected individuals have the sickle cell mutation in both of their beta-globin genes. The mutation causes blood stem cells – which are made in the bone marrow – to produce distorted and rigid red blood cells that resemble a crescent or “sickle” shape. The abnormally shaped red blood cells do not move smoothly through blood vessels, resulting in insufficient oxygen supply to vital organs. Anyone can be born with sickle cell disease, but it occurs more frequently in African Americans and Hispanic Americans.

Inhibition of Th17 Cells Prevents Type 1 Diabetes in Animal Models

Scientists at the Jupiter, Florida campus of The Scripps Research Institute (TSRI) have successfully tested a potent synthetic compound that prevents type 1 diabetes in animal models of the disease. “The animals in our study never developed high blood sugar indicative of diabetes, and beta cell damage was significantly reduced compared to animals that hadn’t been treated with our compound,” said Laura Solt, Ph.D., a TSRI biologist who was the lead author of the study, published in the March 2015 issue of Endocrinology. The article is titled “ROR Inverse Agonist Suppresses Insulitis and Prevents Hyperglycemia in a Mouse Model of Type 1 Diabetes.” Type 1 diabetes is a consequence of the autoimmune destruction of insulin-producing beta cells in the pancreas. While standard treatment for the disease aims to replace lost insulin, the new study focuses instead on the possibility of preventing the initial devastation caused by the immune system—stopping the disease before it even gets started. In the study, the scientists tested an experimental compound known as SR1001 in non-obese diabetic animal models. The compound targets a pair of “nuclear receptors” (RORα and RORg) that play critical roles in the development of a specific population (Th17) of immune cells associated with the disease. “Because Th17 cells have been linked to a number of autoimmune diseases, including multiple sclerosis, we thought our compound might inhibit Th17 cells in type 1 diabetes and possibly interfere with disease progression,” said Dr. Solt. “We were right.” The researchers found that SR1001 eliminated the incidence of diabetes and minimized insulitis, which is the inflammation associated with, and destroyer of, insulin-producing cells, in the treated animals.

New Molecule Targets RIPK1 to Inhibits Cytokine Production and Halt Inflammation; Shows Initial Potential for Preventing MS Progression in Model Systems

Walter and Eliza Hall Institute scientists in Australia have developed a new drug-like molecule that can halt inflammation and has shown promise in preventing the progression of multiple sclerosis (MS). Dr. Ueli Nachbur, Associate Professor John Silke, Associate Professor Guillaume Lessene, Professor Andrew Lew, and colleagues developed the molecule to inhibit a key signal that triggers inflammation. Multiple sclerosis (MS) is an inflammatory disease that damages the central nervous system, including the brain, spinal cord, and optic nerves. There is no cure and there is a desperate need for new and better treatments. Inflammatory diseases such as MS are triggered by an over-active immune system, Dr. Nachbur said. "Inflammation results when our immune cells release hormones called cytokines, which is a normal response to disease," he said. "However, when too many cytokines are produced, inflammation can get out-of-control and damage our own body, all of which are hallmarks of immune or inflammatory diseases." To apply the brakes on this runaway immune response, institute researchers developed a small drug-like molecule called WEHI-345 that binds to and inhibits a key immune signaling protein called RIPK2 (receptor-interacting serine/threonine-protein kinase 2). This prevents the release of inflammatory cytokines. Professor Lew said they examined WEHI-345's potential to treat immune diseases in experimental models of MS. "We treated preclinical models with WEHI-345 after symptoms of MS first appeared, and found it could prevent further progression of the disease in 50 per cent of cases," he said. "These results are extremely important, as there are currently no good preventive treatments for MS." The article was published online on March 17, 2015 in Nature Communications.