Tuesday, June 10, 2014

New details on microtubules and how the anti-cancer drug Taxol works

A pathway to the design of even more effective versions of the powerful anti-cancer drug Taxol has been opened with the most detailed look ever at the assembly and disassembly of microtubules, tiny fibers of tubulin protein that form the cytoskeletons of living cells and play a crucial role in mitosis. Through a combination of high-resolution cryo-electron microscopy (cryo-EM) and new methodology for image analysis and structure interpretation, researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley have produced images of microtubule assembly and disassembly at the unprecedented resolution of 5 angstroms (Å). Among other insights, these observations provide the first explanation of Taxol's success as a cancer chemotherapy agent.

Monday, June 9, 2014

Isis Pharmaceuticals reports positive data from ISIS-GCGRRx Phase 2 study in patients with type 2 diabetes

Isis Pharmaceuticals, Inc.  announced positive data from a Phase 2 study of ISIS-GCGRRx in patients with type 2 diabetes uncontrolled on stable metformin therapy. In this study, patients in the per protocol efficacy population treated with ISIS-GCGRRx achieved statistically significant reductions in measures of glucose control. The absolute mean reductions in hemoglobin A1c (HbA1c) were greater than 2 percentage points>Rx also experienced increased plasma GLP-1 levels. Isis will present additional detail from this study as a late-breaking abstract program at the American Diabetes Association 74th Scientific Sessions. In conjunction, Isis will host an investor event on June 15, 2014 at 7:00 a.m PT. 

"These results reported today represent the potential for a major advance in diabetes therapeutics. ISIS-GCGRRx employs a unique mechanism to treat patients with type 2 diabetes. It is well known that as type 2 diabetes progresses, dysregulated glucagon action becomes a more significant contributor to the disease. The ability of ISIS-GCGRRxto improve glycemic control without causing any clinically significant increases in blood pressure or lipids offers a significant advantage for both patients and treating physicians," said Robert Henry, M.D., chief, VA endocrinology & metabolism and professor of medicine in residence, University of California, San Diego School of Medicine. "The additional effect on increasing GLP-1 means that ISIS-GCGRRx treatment could help to preserve pancreatic function and enhance insulin secretion in diabetic patients."

Saturday, June 7, 2014

Probiotics prevent deadly complications of liver disease, study finds -- ScienceDaily



Probiotics are effective in preventing hepatic encephalopathy in patients with cirrhosis of the liver, according to a new study in Clinical Gastroenterology and Hepatology, the official clinical practice journal of the American Gastroenterological Association. Hepatic encephalopathy is a deterioration of brain function that is a serious complication of liver disease.

Researchers identify drugs to slow progression of idiopathic pulmonary fibrosis

Researchers in separate clinical trials found two drugs slow the progression of idiopathic pulmonary fibrosis, a fatal lung disease with no effective treatment or cure, and for which there is currently no therapy approved by the Food and Drug Administration.

Paul W. Noble, MD, chair of the Department of Medicine at Cedars-Sinai and director of the Women's Guild Lung Institute, is the senior author of the multicenter study that found that the investigational drug pirfenidone significantly slowed the loss of lung function and reduced the risk of death. Pirfenidone was developed by InterMune Inc. and in 2011 was approved by the European Union for the treatment of idiopa Studies Published In New England Journal Of Medicine Identify Promising Drug Therapies For Fatal Lung Disease thic pulmonary fibrosis.

The findings of the ASCEND drug trial are published online by the New England Journal of Medicine and are being presented this week at the International Conference of the American Thoracic Society in San Diego. "What we discovered about the anti-inflammatory and anti-fibrotic properties of pirfenidone offers help and encouragement to so many patients suffering from this relentless disease that robs them of breath and life," said Noble.

Friday, June 6, 2014

Novel drug for patients with inoperable CTEPH shows improvement in international trial

After a year of being treated with a novel drug, patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) and those with persistent or recurrent pulmonary hypertension after an operation for the disease showed sustained improvement in a multicenter, international trial presented at the 2014 American Thoracic Society International Conference.

The drug, riociguat, is a guanylate cyclase stimulator that works independently and in concert with endogenous nitric oxide to induce vasodilation. A long-term extension study, CHEST-2 enrolled patients from CHEST-1, which followed these patients for 16 weeks and achieved its primary endpoint: improved six-minute walking distance (6MWD).

"The pivotal study, CHEST-1, showed significant improvements in exercise capacity and hemodynamics in patients treated with riociguat," said principal investigator Marius Hoeper, MD, of the Hannover Medical School (Germany). "However, the study was relatively short, and CHEST-2 adds important information on the long-term tolerability and efficacy of riociguat in patients with CTEPH."

CTEPH is a relatively rare disease; about 5000 people in the U.S. are diagnosed with the disease each year. It occurs when blood clots from previous episodes of acute pulmonary embolism do not resolve, causing persistent obstruction of the pulmonary vasculature, which may ultimately lead to pulmonary hypertension.

Substance from pine bark is a potential source for treating melanoma

A substance that comes from pine bark is a potential source for a new treatment of melanoma, according to Penn State College of Medicine researchers.

Current melanoma drugs targeting single proteins can initially be effective, but resistance develops relatively quickly and the disease recurs. In those instances, resistance usually develops when the cancer cell's circuitry bypasses the protein that the drug acts on, or when the cell uses other pathways to avoid the point on which the drug acts.

"To a cancer cell, resistance is like a traffic problem in its circuitry," said Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery and director of the Penn State Hershey Melanoma Center. "Cancer cells see treatment with a single drug as a road closure and use a detour or other roads to bypass the closure."

Penn State researchers may have solved this problem by identifying a drug that simultaneously creates many road closures.

The researchers screened 480 natural compounds and identified leelamine, derived from the bark of pine trees, as a drug that can cause this major traffic jam in the cancer cell's circuitry.


"Natural products can be a source of effective cancer drugs, and several are being used for treating a variety of cancers," said Robertson. "Over 60 percent of anti-cancer agents are derived from plants, animals, marine sources or microorganisms. However, leelamine is unique in the way that it acts."

Leelamine could be the first of a new unique class of drugs that will simultaneously target several protein pathways. Researchers found that this drug shuts down multiple protein pathways, such as PI3K, MAPK and STAT3, at the same time in melanoma cells. Thpse pathways are involved in the development of up to 70 percent of melanomas. Protein pathways like these help cancer cells multiply and spread, so shutting them down helps kill the cells.

"The cancer cell is addicted to these pathways," Robertson said. "And when they are shut down, the bypass routes cannot be used. The result is the cancer cells die."

Substance from pine bark is a potential source for treating melanoma

Tuesday, June 3, 2014

New drug offers promising possibility for treating adults with periodontitis

University of Pennsylvania researchers have been searching for ways to prevent, half and reverse periodontitis. In a report published in the Journal of Immunology, they describe a promising new target: a component of the immune system called complement. Treating monkeys with a complement inhibitor successfully prevented the inflammation and bone loss that is associated with periodontitis, making this a promising drug for treating humans with the disease.

George Hajishengallis, a professor in the School of Dental Medicine's Department of Microbiology, was the senior author on the paper, collaborating with co-senior author John Lambris, the Dr. Ralph and Sallie Weaver Professor of Research Medicine in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine. Their collaborators included Tomoki Maekawa, Toshiharu Abe, Evlambia Hajishengallis and Kavita B. Hosur of Penn Dental Medicine and Robert A. DeAngelis and Daniel Ricklin of Penn Medicine.

Earlier work by the Penn team had shown that the periodontal bacterium Porphyromonas gingivalis can hamper the ability of immune cells to clear infection, allowing P. gingivalisand other bacteria to flourish and inflame the gum tissue.

"P. gingivalis has many mechanisms to escape killing by the immune system, but getting rid of inflammation altogether is not good for them because they 'feed' off of it," Hajishengallis said. "So P. gingivalis helps suppress the immune system in a way that creates a hospitable environment for the other bacteria."

The researchers wanted to find out which component of the complement system might be involved in contributing to and maintaining inflammation in the disease. Their experiments focused on the third component of complement, C3, which occupies a central position in signaling cascades that trigger inflammation and activation of the innate immune system.

Monday, June 2, 2014

Screen of existing drugs finds compounds active against MERS coronavirus

Clinicians treating patients suffering from Middle East respiratory syndrome (MERS) currently have no drugs specifically targeted to the MERS coronavirus (MERS-CoV), a virus first detected in humans in 2012 that has since caused 614 laboratory-confirmed infections, including 181 that were fatal, according to the World Health Organization. The case count escalated sharply in the spring of this year, and the first cases in the United States were announced in early May. To address the urgent need for therapies, researchers supported by the National Institutes of Health screened a set of 290 compounds already approved by the U.S. Food and Drug Administration or far advanced in clinical development for other indications to determine if any might also show potential for working against MERS-CoV.

Sunday, June 1, 2014

FDA Approves Dalvance (dalbavancin) to Treat Skin Infections

The U.S. Food and Drug Administration today approved Dalvance (dalbavancin), a new antibacterial drug used to treat adults with skin infections.
Dalvance is intended to treat acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria like Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains) and Streptococcus pyogenes. The treatment is administered intravenously.
Dalvance is the first drug designated as a Qualified Infectious Disease Product (QIDP) to receive FDA approval. Under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act, Dalvance was granted QIDP designation because it is an antibacterial or antifungal human drug intended to treat serious or life-threatening infections.
“Today’s approval demonstrates the FDA’s commitment to encouraging increased development and approval of new antibacterial drugs, providing physicians and patients with important new treatment options,” said Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.
As part of its QIDP designation, Dalvance was given priority review, which provides an expedited review of the drug’s application. Dalvance’s QIDP designation also qualifies it for an additional five years of marketing exclusivity to be added to certain exclusivity periods already provided by the Food, Drug and Cosmetic Act.
Dalvance’s safety and efficacy were evaluated in two clinical trials with a total of 1,289 adults with ABSSSI. Participants were randomly assigned to receive Dalvance or vancomycin, another antibacterial drug. Results showed Dalvance was as effective as vancomycin for the treatment of ABSSSI.
The most common side effects identified in the clinical trials were nausea, headache and diarrhea. In the trials, more participants in the Dalvance group had elevations in one of their liver enzyme tests. The Dalvance drug label provides recommendations on dosage adjustment in patients with renal impairment.

Saturday, May 31, 2014

Combination of metformin and rapamycin shows potential in treating aging and related diseases

A proven approach to slow the aging process is dietary restriction, but new research in the Linus Pauling Institute at Oregon State University helps explain the action of a drug that appears to mimic that process - rapamycin.

Rapamycin, an antibiotic and immunosuppressant approved for use about 15 years ago, has drawn extensive interest for its apparent ability - at least in laboratory animal tests - to emulate the ability of dietary restriction in helping animals to live both longer and healthier.

However, this medication has some drawbacks, including an increase in insulin resistance that could set the stage for diabetes. The new findings, published in the Journals of Gerontology: Biological Sciences, help to explain why that happens, and what could be done to address it.
They suggest that a combination of rapamycin and another drug to offset that increase in insulin resistance might provide the benefits of this medication without the unwanted side effect.

"This could be an important advance if it helps us find a way to gain the apparent benefits of rapamycin without increasing insulin resistance," said Viviana Perez, an assistant professor in the Department of Biochemistry and Biophysics in the OSU College of Science.

"It could provide a way not only to increase lifespan but to address some age-related diseases and improve general health," Perez said. "We might find a way for people not only to live longer, but to live better and with a higher quality of life."

Age-related diseases include many of the degenerative diseases that affect billions of people around the world and are among the leading causes of death: cardiovascular disease, diabetes, Alzheimer's disease and cancer.