Scientists develop new drug to treat obstructive airway diseases

Scientists have developed a new drug (RPL554, see structure) that could treat obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) in two ways at once, according to new research published in The Lancet Respiratory Medicine. RPL554 has the potential to both reverse the narrowing of the airways (bronchodilation) and reduce inflammation quicker and with fewer side effects than current therapies.

“Further longer term studies of RPL554 are now eagerly awaited because this could be one of the most substantial advances for some time in the management of patients with chronic airway obstruction”, writes Professor Jadwiga A Wedzicha from University College London, UK, in a linked Comment.

The unique inhaled dual inhibitor—two actions in a single molecule—works by impeding the ability of two enzymes from the phosphodiesterase family (PDE3 and PDE4) to inhibit processes that help relax airway smooth muscle and reduce inflammation.

For the past 40 years, the mainstay of treatment for asthma and COPD (eg, chronic bronchitis and emphysema) has been inhaled anti-inflammatory drugs (corticosteroids) plus bronchodilators (usually long-acting ß2 agonists). But corticosteroids can have substantial side effects, while long-acting ß2 agonists have come under scrutiny for their risk of worsening asthma symptoms. What is more, most people with severe disease and frequent flare-ups fail to achieve good control of symptoms and new treatments are needed. 

Between February, 2009 and January 3013, four small proof-of-concept clinical trials were done in the Netherlands, Italy, and the UK to assess the safety and efficacy of inhaled RPL554 in healthy participants (39 people) and people with mild-to-moderate asthma (28) and COPD (12).

In COPD patients, a single dose of nebulised RPL554 improved respiratory function, producing a 17% increase in FEV1 (forced expiratory volume at 1 second; which measures the volume of air that can be forcibly exhaled in one second after taking a deep breath)—a bronchodilator response at least as effective as the widely use ß2 agonist Salbutamol.

Ref : http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70187-5/fulltext

Scientists develop new drug to treat obstructive airway diseases

Nintedanib drug to treat NSCLC is submitted for approval from European Medicines Agency

In continuation of my update on NSCLC (non-small cell lung carcinoma)

We know that, Nintedanib (see structure, formerly BIBF 1120; trade name Vargatef) is a small molecule of angiokinase inhibitor class inhibiting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet derived growth factor receptor(PDGFR) being developed by Boehringer Ingelheim for use as an anti-vascular anti-cancer agent.

"We are proud that nintedanib, a compound out of our innovative oncology research programme, is the second compound in our portfolio to be filed with the European Medicines Agency."

Nintedanib drug to treat NSCLC is submitted for approval from European Medicines Agency

Researchers identify C. perfringens type B bacteria believed to trigger multiple sclerosis

A research team from Weill Cornell Medical College and The Rockefeller University has identified a bacterium it believes may trigger multiple sclerosis (MS), a chronic, debilitating disorder that damages myelin forming cells in the brain and spinal cord.

Their study, published in PLoS ONE, is the first to identify the bacterium, Clostridium(C.) perfringens type B, in humans. The scientists say their study is small and must be expanded before a definitive connection between the pathogen and MS can be made, but they also say their findings are so intriguing that they have already begun to work on new treatments for the disease.

"This bacterium produces a toxin that we normally think humans never encounter. That we identified this bacterium in a human is important enough, but the fact that it is present in MS patients is truly significant because the toxin targets the exact tissues damaged during the acute MS disease process," say the study's first author, K. Rashid Rumah, an MD/PhD student at Weill Cornell Medical College, and the study's senior investigator, Dr. Timothy Vartanian, professor of neurology and neuroscience at Weill Cornell Medical College and director of the Judith Jaffe Multiple Sclerosis Center at New York-Presbyterian Hospital/Weill Cornell Medical Center.

"While it is clear that new MS disease activity requires an environmental trigger, the identity of this trigger has eluded the MS scientific community for decades," Dr. Vartanian says. "Work is underway to test our hypothesis that the environmental trigger for MS lays within the microbiome, the ecosystem of bacteria that populates the gastrointestinal tract and other body habitats of MS patients."

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0076359

Researchers identify C. perfringens type B bacteria believed to trigger multiple sclerosis

Combination of heat, doxorubicin drug and nanotech system may improve ovarian cancer treatment

The combination of heat, chemotherapeutic drugs and an innovative delivery system based on nanotechnology may significantly improve the treatment of ovarian cancerwhile reducing side effects from toxic drugs, researchers at Oregon State University report in a new study.

The findings, so far done only in a laboratory setting, show that this one-two punch of mild hyperthermia and chemotherapy can kill 95 percent of ovarian cancer cells, and scientists say they expect to improve on those results in continued research.

The work is important, they say, because ovarian cancer - one of the leading causes of cancer-related deaths in women - often develops resistance to chemotherapeutic drugs if it returns after an initial remission. It kills more than 150,000 women around the world every year.

"Ovarian cancer is rarely detected early, and because of that chemotherapy is often needed in addition to surgery," said Oleh Taratula, an assistant professor in the OSU College of Pharmacy. "It's essential for the chemotherapy to be as effective as possible the first time it's used, and we believe this new approach should help with that."

It's known that elevated temperatures can help kill cancer cells, but heating just thecancer cells is problematic. The new system incorporates the use of iron oxidenanoparticles that can be coated with a cancer-killing drug and then heated once they are imbedded in the cancer cell.

Other features have also been developed to optimize the new system, in an unusual collaboration between engineers, material science experts and pharmaceutical researchers.

A peptide is used that helps guide the nanoparticle specifically to cancer cells, and the nanoparticle is just the right size - neither too big nor too small - so the immune system will not reject it. A special polyethylene glycol coating further adds to the "stealth" effect of the nanoparticles and keeps them from clumping up. And the interaction between the cancer drug and a polymer on the nanoparticles gets weaker in the acidic environment of cancer cells, aiding release of the drug at the right place.

"The hyperthermia, or heating of cells, is done by subjecting the magnetic nanoparticles to an oscillating, or alternating magnetic field," said Pallavi Dhagat, an associate professor in the OSU School of Electrical Engineering and Computer Science, and co-author on the study. "The nanoparticles absorb energy from the oscillating field and heat up."

The result, in laboratory tests with ovarian cancer cells, was that a modest dose of the chemotherapeutic drug, combined with heating the cells to about 104 degrees, killed almost all the cells and was far more effective than either the drug or heat treatment would have been by itself.

Doxorubicin (see structure), the cancer drug, by itself at the level used in these experiments would leave about 70 percent of the cancer cells alive. With the new approach, only 5 percent were still viable.

The work was published in the International Journal of Pharmaceutics, as a collaboration of researchers in the OSU College of Pharmacy, College of Engineering, and Ocean NanoTech of Springdale, Ark. It was supported by the Medical Research Foundation of Oregon, the PhRMA Foundation and the OSU College of Pharmacy.

Combination of heat, doxorubicin drug and nanotech system may improve ovarian cancer treatment

Atorvastatin drug plus zoledronic acid may help treat toxoplasmosis

In continuation of my update on Atorvastatin and Zoledronic acid

Researchers at the University of Georgia have discovered that a combination of two commonly prescribed drugs used to treat high cholesterol and osteoporosis may serve as the foundation of a new treatment for toxoplasmosis, a parasitic infection caused by the protozoan Toxoplasma gondii. They published their findings recently in PLOS Pathogens.

Toxoplasma gondii is a parasite capable of infecting nearly all warm-blooded animals. While healthy human adults usually suffer no lasting ill effects from infection, it can be harmful or fatal to unborn fetuses or those with weakened immune systems.

"For many years, therapies for toxoplasmosis have focused on drugs that target only the parasite," said Silvia Moreno, senior author of the article and professor of cellular biology in UGA's Franklin College of Arts and Sciences. "But in this paper, we show how we can hit the parasite with two drugs simultaneously, one that affects body chemistry in the host and one that affects the parasite."

The UGA researchers discovered that a combination of the cholesterol lowering drugatorvastatin and osteoporosis medication zoledronic acid, both more commonly known by their respective trade names, Lipitor and Zometa, produce changes in the mammalian host and in the parasite that ultimately block parasite replication and spread of the infection.

"These two drugs have a strong synergy," said Moreno, who is also a member of UG

A's Center for Tropical and Emerging Global Diseases. "The mice we treated were cured from a lethal infection using this combination approach."

Moreno and her colleagues began working on this drug combination following a series of experiments with unexpected results. They created a genetically modified version of the parasite in the laboratory that lacked a specific enzyme essential for one of the organism's most basic functions.

Atorvastatin drug plus zoledronic acid may help treat toxoplasmosis

New clinical trial shows increased asthma control with FeNO-guided anti-inflammatory treatment

A new randomised clinical trial shows lower incidence of asthma exacerbations and increased asthma control with Fractional exhaled Nitric Oxide (FeNO)-guided anti-inflammatory treatment. The study has been published on the website of Journal ofAllergy and Clinical Immunology.

A total of 187 non-smoking asthma patients (18-64 years) with perennial allergy and on regular inhaled corticosteroid (ICS) treatment were recruited at 17 primary health care centres in Sweden, randomly assigned to two groups and followed for one year. One group was treated with standard of care whereas treatment of the patients in the other group were guided by FeNO. Aerocrine's patented FeNO test, with the NIOX® MINO® device was used in the study. In the standard of care group FeNO was blinded for both patient and physician.

"FeNO-guided anti-inflammatory treatment enabled the physicians to optimize the treatment with for example inhaled corticosteroids so that both over- and undertreatment can be avoided. This may be a useful tool in long-term management of patients with asthma", says Dr Jörgen Syk, General Practitioner at Runby primary care clinic, Stockholm, Sweden and being the principal investigator in the study.

Overall, FeNO-guided management resulted in improved asthma symptom control and reduced exacerbation frequency in adults with asthma. The FeNO-guided group reported almost 50% fewer asthma exacerbations without an increase in the used average dose of corticosteroids.

Although there was no difference in perceived quality of life (which was the primary endpoint of the study) between the groups, the FeNO-guided group reported fewer symptoms than the group following standard of care treatment.

Ref : http://www.jaci-inpractice.org/article/S2213-2198(13)00352-8/abstract

New clinical trial shows increased asthma control with FeNO-guided anti-inflammatory treatment

Research: Sunscreen provides 100% protection against skin cancer

Researchers found sunscreen provides 100 per cent protection against all three forms ofskin cancer: BCC (basal cell carcinoma); SCC (squamous cell carcinoma); and malignantmelanoma.

Lead researcher Dr Elke Hacker, from QUT's AusSun Research Lab, said sunscreen not only provided 100 per cent protection against the damage that can lead to skin cancer but it shielded the important p53 gene, a gene that works to prevent cancer.

"As soon as our skin becomes sun damaged, the p53 gene goes to work repairing that damage and thereby preventing skin cancer occurring.

"But over time if skin is burnt regularly the p53 gene mutates and can no longer do the job it was intended for - it no longer repairs sun damaged skin and without this protection skin cancers are far more likely to occur."

The study, published in the Pigment Cell & Melanoma Research journal, looked at the impact of sunlight on human skin, both with and without sunscreen, and found no evidence of UV-induced skin damage when proper application of sunscreen (SPF30+) had been applied to exposed area.

"Melanoma is the most lethal form of skin cancer with research showing damage of melanocytes - the pigment-producing cells of the skin - after sun exposure plays a role in the development of skin cancer," Dr Hacker said.

Dr Hacker said the study, funded by Cancer Council Queensland, involved 57 people undergoing a series of skin biopsies to determine molecular changes to the skin before and after UV exposure and with and without sunscreen.

"Firstly we took small skin biopsies of people's unexposed skin. We then exposed two skin sites to a mild burning dose of UV light, one site was applied with sunscreen and the other was not. We again took biopsies of both sites.

"After 24 hours, we took another set of biopsies and compared the skin samples.

"What we found was that, after 24 hours where the sunscreen had been applied, there were no DNA changes to the skin and no impact on the p53 gene," she said. Dr Hacker said this was a significant finding.

"In Australia we have strong standards around sunscreens and their ability to protect against erythema (redness of skin)," Dr Hacker said.

Research: Sunscreen provides 100% protection against skin cancer

Blueberries, Red Grapes May Boost Body's Immune Function

Researchers found that both fruits contain compounds called stilbenoids, which work with vitamin D to increase expression of the human cathelicidin antimicrobial peptide (CAMP) gene, which is involved in immune function.

The stilbenoid compounds included resveratrol in red grapes and pterostilbene in blueberries.

"Out of a study of hundreds of compounds, just these two popped right out," Adrian Gombart, a principal investigator at the Linus Pauling Institute at Oregon State University, said in a university news release.

"Their synergy with vitamin D to increase CAMP gene expression was significant and intriguing," said Gombart, an associate professor in the university's college of science. "It's a pretty interesting interaction."

Gombart and colleagues noted, however, that these findings were made in laboratory cell cultures and do not prove that eating blueberries and red grapes would boost a person's immune function.

The study was published Sept. 17 in the journal Molecular Nutrition and Food Research.

The CAMP gene has been shown to play a key role in the innate immune system -- the body's first line of defense that gives it the ability to fight bacterial infection. The response is especially crucial as many antibiotics become less effective.

Previous research has found a strong association between adequate vitamin D levels and the function of the CAMP gene. This new study suggests that certain other compounds may play a role as well.

Blueberries, Red Grapes May Boost Body's Immune Function - Drugs.com MedNews

New type of antibiotic kills multidrug-resistant germ common to health care settings

A new type of antibiotic called a PPMO, which works by blocking genes essential for bacterial reproduction, successfully killed a multidrug-resistant germ common to health care settings, UT Southwestern Medical Center researchers report.

The technology and new approach offer potential promise against the growing problem of antibiotic resistance, the researchers said.

The pathogen (germ) - called Acinetobacter - can cause infections from pneumonia to serious blood or wound infections, posing greater risk to people with weakened immune systems, chronic lung disease, or diabetes, according to the Centers for Disease Control and Prevention (CDC). Acinetobacter infection mainly affects hospitalized patients or those in long-term care facilities, such as those on ventilators or with urinary cathetersor patients treated for open wounds. The CDC considers Acinetobacter, which is resistant to many antibiotics, one of the top bacterial infection threats in the U.S.

In the study in today's Journal of Infectious Diseases, PPMOs  peptide-conjugated phosphorodiamidate morpholino oligomer, (link for PMOs only) designed to combat two strains of Acinetobacter reduced the number of infectious bacteria in mice by more than 90 percent. Survival of infected mice also improved with the treatment. One of the targeted strains was A. baumannii, a dangerous type that accounts for about 80 percent of reported Acinetobacter infections, according to the CDC.

"We set out to target specific genes in Acinetobacter in an effort to inhibit the bacterium-s growth," said Dr. David Greenberg, assistant professor of internal medicine and microbiology and senior author of the study. "With infections from drug-resistant pathogens rising rapidly, there is an urgent need to come up with new approaches such as the use of PPMOs to spur antibiotic development."

The technology that created the synthetic PPMO could be used to develop similar antibiotics targeting other bacteria and viruses, he added.

"We believe there is a lot of promise in developing new antibiotics that target specific pathogens as opposed to so-called broad-spectrum antibiotics that target whole classes of bacteria," said Dr. Greenberg.

New type of antibiotic kills multidrug-resistant germ common to health care settings

Can Eating Peanut Butter Cut Breast Cancer Risk in Later Life? - Drugs.com MedNews

Eating peanut butter regularly as a preteen and teen girl appears to decrease the risk of developing benign breast disease as an adult, new research has found.

Benign breast disease   noncancerous changes in the breast tissue   is a risk factor for breast cancer, experts agree.

The researchers followed more than 9,000 females, beginning when they were aged 9 to 15 in 1996, until 2010, when they were young women. Eating peanut butter three days a week reduced the risk of developing benign breast disease by 39 percent, said Dr. Graham Colditz, senior study author.

"I think this gives us enormous hope there are strategies we could be following to help prevent breast cancer that we haven't capitalized on yet," said Colditz, the associate director for cancer prevention and control at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, in St. Louis.

The study, published online Sept. 17 in Breast Cancer Research and Treatment, was funded by the Breast Cancer Research Foundation and the U.S. National Institutes of Health.

Benign breast disease is fairly common, and a known risk factor for breast cancer, Colditz said. Before menopause, "about one in four women have a benign lesion, confirmed by biopsy," he said. "It's very clear there is a strong link between the benign lesion and the subsequent risk of invasive breast cancer."

Depending on the characteristics of the benign lesion, he said, benign breast disease could increase breast cancer risk by threefold.

The study participants were part of a long-term, ongoing study on the health effects of diet and exercise in young people. They filled out questionnaires about their diet annually from 1996 until 2001, then four more times until 2010. They also reported if they had been diagnosed with benign breast disease. In all, 112 women said they had.

The researchers looked at foods with vegetable protein and vegetable fats, then focused on individual foods, including peanut butter, peanuts or other nuts, beans and corn.

Can Eating Peanut Butter Cut Breast Cancer Risk in Later Life? - Drugs.com MedNews

New drug candidate found for deadly fungal lung infections

Rappleye's team searched a library of commercially-available small molecules used by other investigators to find new antivirals or anticancer drugs. They performed a high-throughput phenotypic screen of 3,600 compounds looking for agents that inhibited fungal, but not human, cells.

To speed the selection process, Rappleye and Edwards engineered Histoplasma cells with a fluorescent protein that made the cells glow red while inside of a living macrophage -- the type of mammalian immune cell that Histoplasma attacks and in which it reproduces.

As the number of fungal cells increased inside the macrophage, so did the fluorescence and consequently, the cells would glow brighter. However, when a macrophage was exposed to an active compound that prevents Histoplasma reproduction, it maintained the same level of brightness. This allowed the scientists to quickly determine efficacy and toxicity of the drug candidate in a natural environment.

"Not only were we able to visually screen thousands of compounds in just a few weeks, but we were also able to measure the compound's impact in a real, live host cell," said Edwards.

The team narrowed down to a primary candidate called 41F5, which is 60 times more toxic to fungal cells than human cells. Their work was published in the September Antimicrobial Agents and Chemotherapy.

The team is currently working with Werner Tjarks, PhD, a medicinal chemist at Ohio State, to see if the selectivity and toxicity profile can be enhanced further for additional testing. Rappleye is also working with the Ohio State's Technology Commercialization Office (TCO) to potentially commercialize the derivatives from 41F5.

Ref : http://aac.asm.org/content/57/9/4349.abstract?sid=3bdf09cf-45fe-47e2-ad56-66b4ef40ae7e

New drug candidate found for deadly fungal lung infections

Metformin could serve as radiosensitizer to treat patients with stage III non-small cell lung cancer

In continuation of my update on metformin

Treating aggressive lung cancer with the diabetes drug metformin along with radiation and chemotherapy may slow tumor growth and recurrence, suggests new preliminary findings from researchers at the Perelman School of Medicine at the University of Pennsylvania being presented during an oral abstract session October 28 at the 15th World Conference on Lung Cancer.

The pre clinical and clinical results, which have set the stage for a first-of-its-kind prospective study, point to metformin as an effective radiosensitizer-a drug that makes tumor cells more sensitive to radiation therapy-to treat stage III non-small cell lung cancer (NSCLC). Because of poor local response and five-year survival rates around 15 percent in late-stage NSCLC patients, well-tolerated, combination therapies are greatly needed.

The abstract is being presented by Ildiko Csiki, MD, PhD, an assistant professor of Radiation Oncology at Penn's Abramson Cancer Center.

Metformin, the most-widely used drug for type-2 diabetes, has been shown to have anti-cancer effects on a number of cancers, including prostate and colon. It activates AMP-related pathways, leading to inactivation of mTOR and suppression of its downstream effectors, a crucial signaling pathway for proliferation and survival of cancer. However, little data exists to support its role in NSCLC. And its role as a radiosensitizer in lung cancer is even less understood.

Metformin could serve as radiosensitizer to treat patients with stage III non-small cell lung cancer

Two forms of Parkinson's disease identified

A consortium of researchers, headed by a team from the Laboratoire CNRS d'Enzymologie et Biochimie Structurales, is well on the way to providing an explanation. Parkinson’s disease is caused by a protein known as alpha-synuclein, which forms aggregates within neurons, killing them eventually. The researchers have succeeded in characterizing and producing two different types of alpha-synuclein aggregates. Better still, they have shown that one of these two forms is much more toxic than the other and has a greater capacity to invade neurons. This discovery takes account, at the molecular scale, of the existence of alpha-synuclein accumulation profiles that differ from one patient to the next. These results, published on October 10 in Nature Communications, represent a notable advance in our understanding of Parkinson’s disease and pave the way for the development of specific therapies targeting each form of the disease.

Ref : http://www.nature.com/ncomms/2013/131010/ncomms3575/full/ncomms3575.html

Two forms of Parkinson's disease identified

New Drug May Someday Battle Obesity and Diabetes - Drugs.com MedNews

New Drug May Someday Battle Obesity and Diabetes - Drugs.com MedNews

New Cholesterol-Lowering Drug, ALN-PCS Shows Early Promise

An experimental drug that lowers LDL "bad" cholesterol by helping sweep it from the bloodstream appears to be both safe and effective in its first human trial.

The drug known as ALN-PCS reduced cholesterol an average of 40 percent in the small, early study, and, if proven to work in large trials, potentially could replace or complement statins, the researchers said.

Currently, statin drugs such as Lipitor, Crestor and Zocor are widely used to control cholesterol. One heart doctor not involved with the new study said another class of drugs might be useful.

"Cardiovascular disease remains the leading cause of death of men and women globally and reduction of LDL cholesterol with statin medications has been demonstrated to substantially reduce the risk of first or recurrent cardiovascular events," said Dr. Gregg Fonarow, a professor of cardiology at the University of California, Los Angeles.

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61914-5/abstract

New Cholesterol-Lowering Drug Shows Early Promise - Drugs.com MedNews