Thursday, December 31, 2015

Drug compounds target multiple pathways associated with myotonic dystrophy type 1

Efforts to treat myotonic dystrophy type 1, the most common form of muscular dystrophy, are in their infancy. In a new study, researchers report they have added new capabilities to an experimental drug agent that previously defeated only one of DM1's many modes of action. Their retooled compounds interrupt the disease's pathology in three ways.

"We've rationally designed something to target multiple pathways, which is contrary to the traditional thinking in medicinal chemistry, where you have one target, one drug," said University of Illinois chemistry professor Steven Zimmerman, who led the research with graduate students Lien Nguyen and Long Luu. "People are slowly discovering that drugs that hit multiple targets are actually better."

The team reports its findings in the Journal of the American Chemical Society.

DM1 (but not Duchennes muscular dystrophy) results from a genetic error that causes expansion of a region of a particular gene, called DMPK. This gene includes a repeated, three-letter sequence of nucleotides, the gene's chemical building blocks. Normal cells contain as many as 35 of these repeats, but sometimes mutation pushes the number of repeats beyond 50, which can lead to symptoms of the disease. Mutant DMPK genes often continue to expand, amplifying the health problems that can result. In some people, the gene includes as many as 10,000 repeats.

Wednesday, December 30, 2015

Sorafenib increases progression-free survival and disease control rate in NSCLC patients



Sorafenib2DACS.svg


In continuation of my update on Sorafenib

Sorafenib, a tyrosine kinase inhibitor (TKI) targeting the receptors for vascular endothelial growth factor, platelet derived growth factor, and mast/stem cell growth factor, modestly increases progression-free survival (PFS), time to progression, and disease control rate in non-small cell lung cancer (NSCLC) patients who have relapsed or failed two or three previous treatment regimens.

Lung cancer kills more people than breast, prostate, colorectal cancer combined. There are a number of treatment options now available for advanced NSCLC, the most common type of lung cancer, but almost all patients either fail or relapse after a period of clinical benefit. Patients that have relapsed or failed to respond to greater than two previous conventional chemotherapeutic treatments have very limited choices for further therapy.

A team of international investigators from 33 countries in Europe, North and South America, and Asia-Pacific conducted a relatively large phase III, randomized, double-blind, placebo-controlled trial comparing sorafenib plus best supportive care to best supportive care. This MISSION (Monotherapy admInistration of Sorafenib in patientS wIth nOn-small cell luNg cancer) trial was conducted to evaluate the efficacy and safety of sorafenib in the third or fourth-line setting with overall survival (OS) as the primary outcome measure, with PFS and other measures as a secondary endpoints.

The results published in the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer, show that the median PFS was statistically increased in the sorafenib (N=350) vs placebo groups (N=353) (2.8 versus 1.4 months; hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.51-0.72, p<0.0001), however the median OS was not different (8.2 versus 8.3 months; HR 0.99; 95% confidence interval [CI] 0.84-1.17, p=0.47). Time to progression was significantly greater (2.9 versus 1.4 months; HR 0.54; 95% CI 0.45-0.65, p<0.0001) with sorafenib than with placebo as was disease control rate (47.1% versus 24.7%, p=0.00086). Retrospective subgroup analyses showed that epidermal growth factor receptor (EGFR) mutation positive patients receiving sorafenib (N=44) had significantly longer OS (13.9 versus 6.5 months; HR 0.48; 95% CI 0.30-0.76, p=0.002) and PFS (2.7 versus 1.4 months; HR 0.27; 95% CI 0.16-0.46, p<0.001) than those receiving placebo (N=45).

Monday, December 28, 2015

New protein supplement lowers cholesterol, prevents osteoporosis


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Scientists developed a supplement to maintain optimal health that contributes to the growth and development of children and adolescents. It also prevents osteoporosis and certain cancers such as breast and prostate.

Prosoma is a protein supplement made from soy and amaranth, which contributes to lowering cholesterol and preventing osteoporosis, is inexpensive and was created by a group of students from the Interdisciplinary Center for Health Sciences (CICS) at the National Polytechnic Institute in Mexico City

Students Andrea Felix, Eva Fuerte, Ana Ramirez and Cesar Ramos, explained that proteins are made up of chains of amino acids, and are critical to maintaining good health as they contribute to the growth of children and adolescents, also help athletes to develop muscle and optimize their performance.
This food called Prosoma was made with soy and amaranth, vegetables that help lower cholesterol, prevent osteoporosis and certain cancers such as breast and prostate cancer, as opposed to commercial products, it contains no animal protein or chemical additives.

The team of students are specializing in Nutrition at the CICS and ensure that the mixture of these vegetables, added with small pieces of cranberry, form a functional food containing omegas 3 and 6, vitamins A, C, B1, B2 , B3, B6, K, folic acid, vitamins C and E, plus calcium, magnesium, iron, zinc, iodine, copper, selenium, phosphorus, potassium, fluorine and manganese.

According to the innovative development of Prosoma, it could help in combating malnutrition suffered by children between five and 12 years in some regions. It can be consumed by people of all ages, particularly those athletes who wish to strengthen their muscles.

Friday, December 25, 2015

Type 2 diabetes drug significantly reduces hospitalizations, death from heart failure



Empagliflozin.svg

In continuation of my update on Empagliflozin

For the first time, research shows that a type 2 diabetes drug significantly reduces hospitalizations and death from heart failure.

The findings, from a large clinical trial known as EMPA-REG OUTCOME, were presented by Yale professor of medicine and clinical chief of endocrinology, Dr. Silvio E. Inzucchi, at the 2015 American Heart Association (AHA) Scientific Session in Orlando, Florida on Nov. 9.

Many individuals with type 2 diabetes also have heart failure, a condition in which the heart fails to pump blood effectively. Treatment for heart failure is limited and prior efforts to treat patients with type 2 diabetes drugs showed no benefit for heart failure. But a new class of type 2 diabetes drugs (SGLT2 inhibitors) that reduce blood sugar by increasing its excretion in the urine had not been studied.
In the EMPA-REG trial, patients with type 2 diabetes and risk factors for heart disease were randomized to receive once-daily doses of either the glucose-lowering drug empagliflozin (10 mg or 25 mg doses), or a placebo. The drug or placebo was given in addition to standard care.

At the end of the trial period, investigators found that patients treated with the drug experienced reductions in blood sugar and blood pressure, as well as weight loss, compared to those on placebo. They also found major significant reductions in hospitalizations for heart failure (35%); the combined result for heart failure hospitalization or dying from heart disease (34%); and the combined result for being hospitalized or dying from heart failure (39%).

Thursday, December 24, 2015

Drug used to treat Parkinson's and related diseases may delay or prevent macular degeneration



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In continuation of my update on L-DOPA


In a major scientific breakthrough, a drug used to treat Parkinson's and related diseases may be able to delay or prevent macular degeneration, the most common form of blindness among older Americans.

The findings, published in the American Journal of Medicine, are a groundbreaking effort in the fight against age-related macular degeneration (AMD), which affects as many as 11 million Americans. AMD hinders central vision, and even when it does not lead to blindness it can severely reduce the ability to read, drive, and recognize faces.

In the study, supported in part by BrightFocus Foundation, researchers discovered a biological connection between darker pigmented eyes, which are known to be resistant to AMD, and increased levels of a chemical called L-DOPA in those eyes. Since L-DOPA is frequently prescribed for Parkinson's patients, the researchers wanted to know whether patients who received the drug L-DOPA as treatment for Parkinson's or other diseases were protected from AMD. By combing through massive databases of medical chart data, they reported that patients receiving L-DOPA were significantly less likely to get AMD, and when they did, its onset was significantly delayed.

Wednesday, December 23, 2015

New therapy attacks the source of asthma, treats the disease at cellular level

Imagine you suffer from severe asthma, and you've tried every treatment available, but nothing has worked. You still can't breathe. Then a new therapy comes along that attacks the source of the asthma, as opposed to the symptoms, and treats the disease at a cellular level. That's the promise of biologics, and the topic of four presentations at the 2015 ACAAI Annual Scientific Meeting in San Antonio, November 5-9.

"Biologics is definitely something that has piqued the interest of physicians, including allergists, throughout medicine," said Kevin Murphy, MD, ACAAI Fellow and presenter at the meeting. "Traditional asthma treatments don't work for some people, and their asthma is uncontrolled. Biologics is at the cutting edge of treatment because it has the potential to be personalized - to be formulated to treat those cells which are the mechanism, or pathway, that leads to allergic inflammation and makes it so hard for some people to breathe."

Omalizumab is currently the only biologic treatment for asthma that has been approved by the Food and Drug Administration (FDA) for use in the United States, but more are in the pipeline. Allergists hope that in the next few years there could be two or three more drugs approved. Omalizumab is safe for both adults, and children over the age of 12, for treatment of severe asthma.

"It's an exciting time to be an allergist," said allergist Rohit Katial, MD, ACAAI Fellow and presenter at the meeting. "For many years, our primary tools for combatting severe asthma have been either bronchodilators, known as quick-relief medicines, or long-term control medicines which are taken every day to prevent symptoms and attacks. We also use immunotherapy, allergy shots, to reduce the allergic reactions which cause asthma attacks. Biologics target the cells and pathways that cause the allergic inflammation that has been linked to asthma."

Tuesday, December 22, 2015

Dementia drug 'keeps patients out of nursing homes'



Brain



Donepezil skeletal.svg

Donepezil is used to slow the decline of people with mild to moderate dementia.
But it tends not to be given to patients in the late stage of the disease, because of a lack of evidence that it helps.

However the study of 295 people led by University College London experts, has produced evidence that challenges that.
The participants were split into groups with some being given donepezil, some another dementia drug memantine and others a dummy pill, the journal Lancet Neurology reported.

Of those given donepezil, sold under the brand name Aricept, 20% were living in a nursing home within a year, compared to 37% of those not given it.

The study is part of a follow-up analysis of data first collected three years ago, which showed some improvement when the drug was given to people with moderate to late-stage dementia.
Benefits

Researchers said more investigation was needed to fully unpick the reasons for a nursing home admission.
But they said their study provided evidence that needed to be considered when it comes to prescribing practices.
Some 60,000 people in the UK take the drug which helps to maintain brain function and the ability to cope with everyday activities such as eating and dressing.
About 70% of older people in care homes and nursing homes have dementia - with the average cost of that care ranging between £30,732 and £34,424.
Although such care is means-tested, a large chunk of the cost is borne by the individual.
In comparison, a year's supply of donepezil can cost as little as £21.59, according to the Alzheimer's Society.

Lead researcher Prof Robert Howard said: "Our previous work showed that, even when patients had progressed to the moderate or severe stages of their dementia, continuing with donepezil treatment provided modest benefits in cognitive function and in how well people could perform their daily activities.

"Our new results show that these benefits translate into a delay in becoming dependent on residential care, an event that many people dread."

Dr Doug Brown, director of research and development at the Alzheimer's Society, which co-funded the trial together with the Medical Research Council (MRC), said: "These robust findings are of real significance to people with dementia who want to continue living at home for as long as possible. We urge clinicians to consider the implications of this research and adjust their prescribing patterns accordingly."

Ref : http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(15)00258-6/abstract

Thursday, December 17, 2015

IMBRUVICA (ibrutinib) wins Prix Galien USA 2015 Award in Best Pharmaceutical Agent category



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In continuation of my update ibrutinib


Today, IMBRUVICA® (ibrutinib) was awarded the prestigious Prix Galien USA 2015 Award in the category of Best Pharmaceutical Agent. The Prix Galien Award is considered to be the industry's highest accolade and recognizes the vital technical, scientific and clinical research skills necessary to develop medicines. IMBRUVICA is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company, and the win recognizes the work of both companies.

"Our journey with ibrutinib and our strategic partner, Pharmacyclics, has been exciting and rewarding since day one," said Peter F. Lebowitz, M.D., Ph.D., Global Head, Oncology, Janssen Research & Development, LLC. "We're honored to be recognized by the awards committee, especially among such a remarkable field of innovative compounds."
To qualify, medicines needed to be deemed innovative in the field of medicine and approved by the U.S. Food and Drug Administration (FDA) within the past five years. Since the inception of the award, Janssen has received 26 Prix Galien awards, including three in the U.S. and four at the international level.

The Prix Galien was created in France in 1970 in honor of Galen, the father of medical science and modern pharmacology. Worldwide, the Prix Galen is regarded as the equivalent of the Nobel Prize in biopharmaceutical and medical technology research, honoring significant advances in pharmaceutical research. Until the inception of Prix Galien, this particular field of research was largely unrecognized. Following the success of the original Prix Galien award in France more than 40 years ago, several additional countries have instituted local versions of the award.

Wednesday, December 16, 2015

Lithium chloride could offer effective treatment against osteoarthritis

Bioengineers from Queen Mary University of London (QMUL) have shown for the first time that lithium chloride, a common drug used to treat mental health disorders, could offer an effective treatment against osteoarthritis by disrupting the length of the cells' antennae called primary cilia.

Publishing in the journal FASEB, the scientists show that medical manipulation of the primary cilia, which are tiny hair-like structures protruding from the surface of most human cells, disrupts a key biological process called 'Hedgehog Signalling'.

Osteoarthritis is a painful disease affecting millions of people. It results from the cartilage breaking down at the joints and leads to difficulties in moving around and being active. Being able to control Hedgehog Signalling has previously been shown to reduce the severity of arthritis.

Monday, December 14, 2015

Praziquantel treatment safe for pregnant women after first trimester



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A study by Rhode Island Hospital researchers confirmed that a drug used to treat a disease afflicting millions of people in developing countries is safe to give pregnant women following their first trimester. The finding could prove critical to the care of pregnant women and lactating women with schistosomiasis, a disease caused by a parasitic worm, who were denied the drug out of concern for their health and the health of their fetuses.


Authored by Jennifer F. Friedman, M.D., Ph.D., MPH, director of clinical studies for the Center for International Health Research at Rhode Island Hospital, the study found that praziquantel does not lead to adverse events for the pregnant woman or her newborn. The study was published today in The Lancet Infectious Diseases.

"Millions of women, many of whom are in a multi-year, cyclical pattern of pregnancy and breast-feeding, are denied praziquantel," said Friedman. "The accumulation of evidence shows that commencement of this treatment after the first trimester does not adversely affect the mother or fetus. We wanted to conduct this study to demonstrate that this drug is safe after the first trimester, and we remain hopeful that public health policies will change. Deferring treatment only exacerbates the morbidity of the patients."

Friday, December 11, 2015

Mylan announces U.S. launch of generic Fusilev for Injection



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Mylan N.V. (Nasdaq: MYL) today announced the U.S. launch of Levoleucovorin Calcium Injection 10 mg (base)/mL; 175 mg (base)/17.5 mL and 250 mg (base)/25 mL Single-use Vials, which is the generic version of Spectrum Pharmaceuticals' Fusilev® for Injection. Mylan received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product, which is indicated for rescue use after high-dose methotrexate therapy in osteosarcoma. Levoleucovorin is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists.

Levoleucovorin Calcium Injection 10 mg (base)/mL; 175 mg (base)/17.5 mL and 250 mg (base)/25 mL Single-use Vials had U.S. sales of approximately $200 million for the 12 months ending June 30, 2015, according to IMS Health.

Currently, Mylan has 259 ANDAs pending FDA approval representing $98.5 billion in annual brand sales, according to IMS Health. Fifty of these pending ANDAs are potential first-to-file opportunities, representing $33.4 billion in annual brand sales, for the 12 months ending December 31, 2014, according to IMS Health.

Mylan announces U.S. launch of generic Fusilev for Injection

Thursday, December 10, 2015

Early trial results in lung cancer



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Results from early phase trials investigating different therapeutic agents in lung cancer patients were presented during the third Presidential Session at the European Cancer Congress in Vienna, Austria. Here we summarise two studies reported at the session.

Erlotinib (structure) plus bevacizumab promising in EGFR T790M-positive advanced NSCLC patients. 

Rolf Stahel, from University Hospital Zurich in Switzerland, presented the findings of the BELIEF trial [1] on behalf of his fellow investigators from the Spanish Lung Cancer Group and the European Thoracic Oncology Platform. The phase II trial enrolled 109 patients with metastatic or locally advanced non-squamous non-small-cell lung cancer (NSCLC) harbouring activating epidermal growth factor receptor (EGFR) mutations (either the exon 19 deletion or the exon 21 L858R point mutation).

Of these, 37 (33.9%) patients also carried the EGFR T790M mutation at baseline, while the remaining 72 participants were negative for T790M.

Patients were treated with a combination of everolimus and bevacizumab on the basis of previous preclinical results suggesting that inhibiting both the EGFR and vascular EGFR pathways could be beneficial in the presence of the T790M mutation, explained Stahel.

After a median follow-up of 17.5 months, progression-free survival (PFS) was a median of 13.8 months in the overall cohort, with times of 16.0 and 10.5 months for the T790M-positive and -negative groups, respectively. The corresponding 1-year PFS rates were 56.7%, 72.4% and 49.4%.

Complete responses were achieved by 6.4% of all study participants, 8.1% of those positive for T790M and 5.6% of T790M-negative patients, while partial responses were achieved by 69.7%, 62.2% and 73.6% of patients, respectively.

Wednesday, December 9, 2015

New synthetic process helps study key molecule involved in diabetes, inflammation, aging



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A synthetic process developed at Yale University will allow researchers to study a key molecule involved in diabetes, inflammation, and human aging.

The new process synthesizes glucosepane, which is considered a critical chemical link in both diabetes and aging. It is also an independent risk factor for long-term microvascular complications in diabetes.

In a study published this week in the journal Science, senior author David Spiegel and his colleagues describe the new synthesis, as well as a new synthetic methodology, which may have applications beyond the current research.

"Glucosepane forms in all human beings during the aging process, and also forms during various diseases, including diabetes," said Spiegel, a professor of chemistry and pharmacology at Yale. "It is unknown what role glucosepane might play in aging and in these diseases, but several hypotheses have been proposed. With access to synthetic glucosepane, we will now be able to generate tools to examine the role this molecule plays in human health and also, perhaps, develop molecules to inhibit or reverse its formation."
Until now, it has been difficult to study glucosepane effectively. There is a scarcity of chemically homogeneous glucosepane available for scientists to examine -- due to its unusual structure and properties -- and researchers have been forced to rely on time-consuming extraction protocols to obtain usable material.

Glucosepane contains a rare isomer of imidazole, which has never before been observed in natural molecules, other than those in the glucosepane family. Spiegel and his colleagues developed a new methodology for synthesizing this imidazole form. The process requires only eight steps.

In an accompanying article in Science, Dale L. Boger of the Scripps Research Institute wrote that the Yale study represents "an important, yet largely underexplored, frontier for chemistry with broad implications in human health." Boger said Spiegel's methodology "is important in its own right and will find applications well beyond that envisioned by the authors."

Tuesday, December 8, 2015

Study could lead to better understanding of metabolic processes behind type 2 diabetes

Scientists in Sweden have discovered that human intestinal flora regulates the levels of the body's main antioxidant, glutathione, which fights a host of diseases. The findings could lead to new probiotic-delivering foods, and a better understanding of the metabolic processes behind diseases such as type 2 diabetes.

Chalk up another reason why your gut bacteria is so critical to your health — and why it could be the key to preventing a host of diseases. Scientists in Sweden have discovered that human intestinal flora regulates the levels of the body's main antioxidant, glutathione, which fights a host of diseases.

The study could lead to new probiotic-delivering foods, and a better understanding of the metabolic processes behind diseases such as type 2 diabetes, says co-author Adil Mardinoglu, a systems biology researcher at Stockholm's KTH Royal Institute of Technology.

Published in the scientific journal, Molecular Systems Biology, the findings help complete our understanding of how nonessential amino acids are synthesized to equip the body's cells with detoxifying agents and antioxidants, Mardinoglu says.

Monday, December 7, 2015

Cranberry juice consumption may protect against cardiovascular disease

In continuation of my updates on Cranberries

Results from a new study presented at the Cranberry Health Research Conference preceding the annual Berry Health Benefits Symposium 2015 in Madison, WI, revealed that cranberry juice consumption may play a role in protecting against cardiovascular disease. Presented by principal investigator, Ana Rodriguez-Mateos, PhD, from the Division of Cardiology, Pulmonology and Vascular Medicine at the University Duesseldorf, Germany, the research uncovered a potent, dose-dependent relationship between cranberry juice and improved vascular function. Because vascular dysfunction, including limitations in blood flow, is a central feature in the development of atherosclerosis - improving vascular function can have a powerful, beneficial effect on a person's cardiovascular health.

"Cranberry juice is a rich source of phytonutrients, including proanthocyanidins, anthocyanins and phenolic acids," explains Dr. Rodriguez-Mateos. "Due to this robust profile of polyphenols, our team sought to evaluate the immediate vascular impact of drinking one, 450 ml (or 16 ounces) glass of cranberry juice with a different range of concentrations of cranberry-polyphenols."


Friday, December 4, 2015

Veltassa (patiromer for oral suspension) gets FDA approval for treatment of hyperkalemia



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The U.S. Food and Drug Administration today approved Veltassa (patiromer for oral suspension) to treat hyperkalemia, a serious condition in which the amount of potassium in the blood is too high.

"Too much potassium in the blood can lead to dangerous, even fatal, changes in heart rhythm," said Norman Stockbridge, M.D., Ph.D., director of the Division of Cardiovascular and Renal Products in the FDA's Center for Drug Evaluation and Research. "It is important to have treatment options for hyperkalemia available to patients."

Potassium, a mineral that is delivered to the body by food, is needed for cells to function properly. The kidneys remove potassium from the blood to maintain a proper balance of potassium in the body. But when the kidneys are not able to remove enough potassium from the blood, the level of potassium can get too high. Hyperkalemia typically occurs in patients with acute or chronic kidney disease or heart failure, particularly in those who are taking drugs that inhibit the renin-angiotensin-aldosterone system, which regulates blood pressure and fluid balance in the body.


Thursday, December 3, 2015

Orange pigment may have potential as anti-cancer drug



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An orange pigment found in lichens and rhubarb called parietin may have potential as an anti-cancer drug, scientists at Winship Cancer Institute of Emory University have discovered.

The results are scheduled for publication on October 19 in Nature Cell Biology.

Parietin, also known as physcion, could slow the growth of and kill human leukemia cells obtained directly from patients, without obvious toxicity to human blood cells, the authors report. The pigment could also inhibit the growth of human cancer cell lines derived from lung and head and neck tumors when grafted into mice.
A team of researchers led by Jing Chen, PhD, discovered the properties of parietin because they were looking for inhibitors for the metabolic enzyme 6PGD (6-phosphogluconate dehydrogenase). 6PGD is part of the pentose phosphate pathway, which supplies cellular building blocks for rapid growth. Researchers have already found 6PGD enzyme activity increased in several types of cancer cells.

"This is part of the Warburg effect, the distortion of cancer cells' metabolism," says Chen, professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute. "We found that 6PGD is an important metabolic branch point in several types of cancer cells."

This work represents a collaboration among three laboratories at Winship led by Chen, Sumin Kang, PhD, assistant professor of hematology and medical oncology, and Jun Fan, PhD, assistant professor of radiation oncology. Co-first authors are postdoctoral fellows Ruiting Lin, PhD, and Changliang Shan, PhD, and former graduate student Shannon Elf, PhD, now at Harvard.

The Winship team obtained cancer cells from a patient with acute lymphoblastic leukemia, and found doses of physcion/parietin that could kill half the leukemia cells in culture within 48 hours, while the same doses left healthy blood cells unscathed. A more potent derivative of the pigment called S3 could cut the growth of a lung cancer cell line by a factor of three over 11 days, when the cells were implanted into mice.

Ref : http://www.emoryhealthsciblog.com/tag/jing-chen/

Ixazomib’s phase 3 study in relapsed/refractory multiple myeloma presented



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Takeda Pharmaceutical Company Limited today announced that it will present Phase 3 data from the TOURMALINE-MM1 ixazomib clinical trial at the 57th American Society of Hematology (ASH) Annual Meeting to be held in Orlando, Florida from December 5 to 8, 2015.

A total of 19 company-sponsored abstracts representing the breadth and depth of Takeda’s hematology-oncology portfolio were accepted for presentation at this year’s meeting.

We are particularly looking forward to this year’s ASH annual meeting. We will be presenting pivotal data on the ixazomib program, as well as the five year overall survival data for ADCETRIS in relapsed/refractory Hodgkin lymphoma.

The success of these two programs, in addition to data we will be presenting on VELCADE and our pipeline, is the realization of decades of commitment to patients with hematological malignancies.

Dixie-Lee Esseltine, MD, FRCPC, Vice President, Oncology Therapeutic Area Unit, Takeda.
“This is the first time Phase 3 data will be presented for ixazomib, an oral, once-weekly proteasome inhibitor which, if approved, would enable the first all-oral triplet regimen containing a proteasome inhibitor for the treatment of relapsed/refractory multiple myeloma,” said TOURMALINE-MM1 Principal Investigator Philippe Moreau, M.D., University of Nantes, France.

“In working with Takeda Oncology on the evolution of proteasome inhibition, we continue to strive towards providing new options to address the unmet needs of patients with multiple myeloma.”

Ixazomib is the first oral proteasome inhibitor in late stage clinical development. The TOURMALINE-MM1 study is an international, randomized, double-blind, placebo-controlled Phase 3 clinical trial which was designed to evaluate the superiority of once-a-week oral ixazomib plus lenalidomide and dexamethasone vs. placebo plus lenalidomide and dexamethasone in adult patients with relapsed and/or refractory multiple myeloma.

Ixazomib has been granted Priority Review from the U.S. Food and Drug Administration (FDA) and Accelerated Assessment by the Committee for Medicinal Products for Human Use of the European Medicines Agency , respectively, validating the profound and continuing unmet need for new multiple myeloma treatments.

Wednesday, December 2, 2015

New study compares effectiveness of clozapine with standard antipsychotics in adults with schizophrenia

Skeletal formula of clozapine



In real-world settings, patients with schizophrenia whose symptoms do not respond to standard antipsychotic medications have better outcomes if they are switched to clozapine instead of another standard antipsychotic. They have fewer hospitalizations, stay on the new medication longer, and are less likely to need to use additional antipsychotics. These findings were published today in the American Journal of Psychiatry.

Schizophrenia is a serious mental disorder affecting up to one percent of the adult population. Antipsychotics are effective at relieving symptoms for most patients, but up to 30% do not respond well to standard treatments and are considered to have treatment-resistant schizophrenia. While trials have indicated that clozapine is effective for these cases, the effectiveness of clozapine in clinical practice has not previously been studied in depth.
Often when one traditional antipsychotic medication does not work, clinicians change to another traditional antipsychotic. Clozapine is often seen as a drug of last resort, although it is the only medication approved by the FDA for treatment-resistant schizophrenia.

The new study was conducted using national Medicaid data from 6,246 patients whose treatment patterns were consistent with treatment resistance. It is the largest study directly comparing the effectiveness of clozapine with standard antipsychotics in this population in routine practice settings.

The results are encouraging and timely because the FDA recently broadened access to clozapine. In the past access was limited, in part because of the risk of agranulocytosis, a condition that can make people susceptible to infections. A system has been in place for 25 years to successfully manage the risks of agranulocytosis, using regular monitoring of white blood cell levels. Leading clinicians thus believe the limits on use of clozapine have been overly restrictive. The new FDA rules still require regular blood monitoring, but allow prescribers to make decisions based on benefits and risks for individual patients rather than rigidly following universal standards.

Yoga exercise as effective as traditional pulmonary rehab in improving pulmonary function in COPD patients

Researchers from the Department of Pulmonary Medicine and Sleep Disorders and All India Institute of Medical Sciences, New Delhi, India, studied the effects of yoga as a form of pulmonary rehabilitation on markers of inflammation in the body. Results from this study showed yoga exercises provide improvements that are just as effective as traditional pulmonary rehabilitation methods in improving pulmonary function, exercise capacity, and indices of systemic inflammation.

Sixty patients with COPD were randomly divided into two groups, one of which was taught yoga exercises while the other underwent a structured pulmonary rehabilitation program. These groups were tested on shortness of breath, serum inflammation, and lung function tests. Each group participated in 1 hour of training twice a week for the first 4 weeks, then training every 2 weeks for 8 weeks, and the remaining weeks were at home. Results showed that yoga and pulmonary rehabilitation exercises resulted in similar improvements in pulmonary function, 6-minute walk distance, Borg scale, severity of dyspnea, quality of life, and levels of C-reactive protein after 12 weeks of training.

"This study suggests yoga may be a cost-effective form of rehabilitation that is more convenient for patients," said Mark J. Rosen, MD, Master FCCP, CHEST Medical Director. "The authors recommended adoption of yoga programs as an option as part of long-term management of COPD. These findings should be confirmed in new studies and the potential mechanisms explored."

Tuesday, December 1, 2015

BDSI announces FDA approval of BUNAVAIL sNDA for manufacturing specification change



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BioDelivery Sciences International, Inc. (NASDAQ: BDSI) announced that the U.S. Food and Drug Administration (FDA) has approved the company's Supplemental New Drug Application (sNDA) for a manufacturing specification change for BUNAVAIL® (buprenorphine and naloxone) buccal film (CIII).


The approval allows for the immediate release of BUNAVAIL inventory to wholesalers. BDSI will be shipping product to wholesalers this morning which should make product available in pharmacies as early as Friday.
The newly released product supplies are expected to satisfy current and anticipated demand, which has increased following the October 1 initiation of a contract providing exclusive, preferred formulary status for BUNAVAIL for Medicaid patients in the state of Tennessee.

"All of us at BDSI want to thank the Division of Anesthesia, Analgesia and Addiction Products at FDA for working with us in an expeditious and collaborative fashion to help allow patients benefiting from BUNAVAIL treatment to maintain uninterrupted availability," said Dr. Mark A. Sirgo, President and Chief Executive Officer. "We also want to thank all of the patients, physicians and other health providers, including pharmacists, for their patience and support during this period of inconvenience."

Monday, November 30, 2015

Medical experts launch crowd funding project to investigate effect of malaria drug on colorectal cancer


Artesunate.svg


In continuation of my update on Artesunate


Medical experts investigating whether a common malaria drug could have a significant impact on colorectal cancer have launched a crowd funding project to fund their work.

Scientists at St George's, University of London, and St George's Hospital, are in the second phase of research into whether the malaria drug artesunate, can have a positive effect on colorectal cancer patients by reducing the multiplication of tumour cells and decreasing the risk of cancer spreading or recurring after surgery. If it does the drug could be used to provide a cheap adjunct to current expensive chemotherapy.

Artesunate is derived from the plant Artemisia Annua also known as Sweet Wormwood. The Chinese scientist Tu Youyou whose research in the 1960s led to the development of artesunate from a plant used in Chinese traditional medicine, was recently awarded the Nobel Prize 2015.


Over one million patients are diagnosed with colorectal cancer globally each year. Colorectal cancer is the third most common cancer in men and the second most common cancer in women and is a leading cause of mortality. In the UK,110 new cases are diagnosed daily, with older patients particularly at risk of death (Ferlay et al 2014). Current treatments involve complex combinations of surgery, chemotherapy and radiotherapy.

Unfortunately all these measures have not increased overall survival rates beyond 60% at the 5 year stage after patients receive a diagnosis. New treatments are urgently needed to improve survival rates. Developing new, effective drugs however can take many years and sometimes even decades. Repurposing safe and established existing drugs for cancer treatment is therefore gaining interest amongst the scientific community.

Friday, November 27, 2015

Research: Epigenetic factor reduces sensitivity of breast cancer cells to common cancer drug


Lapatinib2DACS.svg

In continuation of my update on lapatinib


A surprising, paradoxical relationship between a tumor suppressor molecule and an oncogene may be the key to explaining and working around how breast cancer tumor cells become desensitized to a common cancer drug, found researchers at the Perelman School of Medicine at the University of Pennsylvania. The drug, lapatinib, activates the suppressor called FOXO, in HER2+ breast cancer cells, but then FOXO becomes a turncoat molecule, working with an epigenetic regulator that controls gene expression. This drug-triggered relationship induces the expression of the oncogene c-Myc, leading to reduced sensitivity to the cancer drug and eventually relapse. They published their cover article today in Cancer Cell.

"We found that an epigenetic pathway is crucial for growth of HER2+ cells and this epigenetic factor reduces sensitivity of the cancer cells to lapatinib, a HER2 inhibitor," said senior author Xianxin Hua, MD, PhD, a professor of Cancer Biology. "We need to understand how the body initially responds to these drugs and why there is a relapse and devise a new tool to fix that."
Human epidermal growth factor receptor 2 (HER2) is upregulated in a subset of human breast cancers. The HER2 pathway is mutated in many cancers, which drives tumors, but inhibitors of this pathway, such as lapatinib, have only limited success because cancer cells quickly adapt.

FOXO was normally thought of as the "good guy" molecule that controls cancerous cell growth, while c-Myc, the cancer-promoting molecule, the "bad guy." However, FOXO becomes the agent that desensitizes cells to cancer drugs, so this "good guy" molecule is converted to a "bad guy," during the treatment of the cancer cells with the anti-cancer drug.

"Now that we know about this triangle among FOXO, c-Myc, and the epigenetic pathway, we can stop c-Myc with an epigenetic inhibitor," Hua said. "Multiple epigenetic regulators participate in the drug-desensitizing pathway, so they could serve as new targets to improve therapy for this type of cancer."

Thursday, November 26, 2015

Investigational antiviral drug effectively treats Lassa virus infection in guinea pigs

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We know that, Favipiravir, also known as T-705 or Avigan, is an experimental antiviral drug being developed by Toyama Chemical of Japan with activity against many RNA viruses. Like some other experimental antiviral drugs (T-1105 and T-1106), it is a pyrazinecarboxamide derivative. Favipiravir is active against influenza viruses, West Nile virus, yellow fever virus, foot-and-mouth disease virus as well as other flaviviruses, arenaviruses, bunyaviruses and alphaviruses.[1Activity against enteroviruses and Rift Valley fever virus has also been demonstrated.

The mechanism of its actions is thought to be related to the selective inhibition of viral RNA-dependent RNA polymerase.[4] Favipiravir does not inhibit RNA or DNA synthesis in mammalian cells and is not toxic to them.[1]

In 2014, favipiravir was approved in Japan for stockpiling against influenza pandemics
Favipiravir, an investigational antiviral drug currently being tested in West Africa as a treatment for Ebola virus disease, effectively treated Lassa virus infection in guinea pigs, according to a new study from National Institutes of Health (NIH) scientists and colleagues. Lassa fever is endemic to West Africa and affects about 300,000 people annually, killing roughly 5,000. In some parts of Sierra Leone and Liberia, it is believed nearly 15 percent of people admitted to hospitals have Lassa fever, according to the Centers for Disease Control and Prevention. No vaccine or licensed treatment exists for Lassa fever, although ribavirin, licensed for hepatitis C treatment, has been used with limited success. In the new study, published Oct. 12, 2015, in Scientific Reports, favipiravir not only effectively treated guinea pigs infected with Lassa virus, it also worked better than ribavirin.

Two days after infecting groups of guinea pigs with a lethal dose of Lassa virus, the scientists treated the rodents daily for two weeks with either ribavirin, low doses of favipiravir, or high doses of favipiravir. They also evaluated the effect of high-dose favipiravir in the rodents that began treatment five, seven or nine days after infection. All of the animals that received high-dose favipiravir were completely protected from lethal infection; animals treated seven or nine days after infection had begun showing signs of disease, but their conditions quickly improved when treatment began. Those animals in the low-dose favipiravir group showed mild to moderate signs of disease, but those symptoms resolved after about one week of treatment. The animals treated with ribavirin appeared normal during the treatment phase but developed severe disease shortly after treatment ended.


Wednesday, November 25, 2015

CU Cancer Center study reports 'robust antitumor activity' of TAK-733 drug in mouse models of colorectal cancer


In continuation of my update on TAK-733
http://pubchem.ncbi.nlm.nih.gov/image/


A University of Colorado Cancer Center study recently published online ahead of print in the journal Oncotarget reports "robust antitumor activity" of the drug TAK-733 in cells and mouse models of colorectal cancer. In all, 42 of 54 tested cell lines were sensitive to the drug, as were 15 of 20 tumors grown on mice from patient samples. Nine of these patient-derived tumors showed regression, meaning that tumor tumors shrank in response to the drug.

"This was a large preclinical study that showed good activity for the drug and gave preliminary evidence for a potential biomarker that could predict which tumors would respond best to the drug," says Christopher Lieu, MD, investigator at the CU Cancer Center and assistant professor of medical oncology at the University of Colorado School of Medicine.

Specifically, the drug intercedes in the MAPK signaling pathway, a cascade of cellular communication that controls cell growth and survival and is frequently altered in many cancers (especially including melanoma, non-small cell lung cancer, and colorectal cancer). The drug does this by silencing an essential link in this signaling chain, namely the molecule MEK. Without activity of the MEK kinase, MAPK signaling cannot occur and instead of surviving and proliferating, cancer cells dependent on this pathway die.

A handful of successful MEK kinase inhibitors exist, including trametinib and selumetinib.

"The preclinical results for TAK-733 were fairly impressive. We had high hopes that TAK-733 could be a next-generation MEK inhibitor that might support or replace the use of current drugs," Lieu says.

The study seemed a perfect precursor to a human clinical trial of TAK-733 in colorectal cancer.


Tuesday, November 24, 2015

Sense oligonucleotide antidote reverses actions of antisense antithrombotic drug, prevents bleeding


Researchers from Isis Pharmaceuticals (Carlsbad, CA) and Prysis Biotechnologies (Pudong, Shanghai, China) have demonstrated proof-of-concept for using a sense oligonucleotide to undo the effects of an antisense drug, an antithrombotic agent in this novel study. The sense oligonucleotide antidote reversed the actions of the antisense antithrombotic drug in the mouse model and prevented the bleeding that commonly occurs with anti-coagulation therapy, as described in an article in Nucleic Acid Therapeutics, a peer-reviewed journal from Mary Ann Liebert, Inc. publishers. The article is available free on the Nucleic Acid Therapeutics website until November 13, 2015.

Jeff Crosby, Chenguang Zhao, Hong Zhang, A. Robert MacLeod, Shuling Guo, and Brett Monia treated mice with an antisense oligonucleotide drug designed to suppress the ability of liver and blood cells to produce prothrombin, a protein required for blood to coagulate. Subsequent treatment with a prothrombin sense oligonucleotide antidote led to a dose-dependent reversal of the antisense drug activity and the return of prothrombin to normal levels. The authors describe the study design and the implications of their findings in the article "Reversing Antisense Oligonucleotide Activity with a Sense Oligonucleotide Antidote: Proof of Concept Targeting Prothrombin."

"An elegant demonstration of the feasibility of reversing the effects of an antisense oligonucleotide in vivo by administering an antidote oligonucleotide," says Executive Editor Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI. "It will be fascinating to now see how the chemistry can be optimized to achieve translation to clinical efficacy."





Sense oligonucleotide antidote reverses actions of antisense antithrombotic drug, prevents bleeding

Monday, November 23, 2015

Tamoxifen drug clears MRSA, reduces mortality


In continuation of my update on Tamoxifen
Tamoxifen2DACS.svg


Researchers at University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences have found that the breast cancer drug tamoxifen gives white blood cells a boost, better enabling them to respond to, ensnare and kill bacteria in laboratory experiments. Tamoxifen treatment in mice also enhances clearance of the antibiotic-resistant bacterial pathogen MRSA and reduces mortality.

The study is published October 13 by Nature Communications.

"The threat of multidrug-resistant bacterial pathogens is growing, yet the pipeline of new antibiotics is drying up. We need to open the medicine cabinet and take a closer look at the potential infection-fighting properties of other drugs that we already know are safe for patients," said senior author Victor Nizet, MD, professor of pediatrics and pharmacy. "Through this approach, we discovered that tamoxifen has pharmacological properties that could aid the immune system in cases where a patient is immunocompromised or where traditional antibiotics have otherwise failed."

Tamoxifen targets the estrogen receptor, making it particularly effective against breast cancers that display the molecule abundantly. But some evidence suggests that tamoxifen has other cellular effects that contribute to its effectiveness, too. For example, tamoxifen influences the way cells produce fatty molecules, known as sphingolipids, independent of the estrogen receptor. Sphingolipids, and especially one in particular, ceramide, play a role in regulating the activities of white blood cells known as neutrophils.

"Tamoxifen's effect on ceramides led us to wonder if, when it is administered in patients, the drug would also affect neutrophil behavior," said first author Ross Corriden, PhD, project scientist in the UC San Diego School of Medicine Department of Pharmacology.

To test their theory, the researchers incubated human neutrophils with tamoxifen. Compared to untreated neutrophils, they found that tamoxifen-treated neutrophils were better at moving toward and phagocytosing, or engulfing, bacteria. Tamoxifen-treated neutrophils also produced approximately three-fold more neutrophil extracellular traps (NETs), a mesh of DNA, antimicrobial peptides, enzymes and other proteins that neutrophils spew out to ensnare and kill pathogens. Treating neutrophils with other molecules that target the estrogen receptor had no effect, suggesting that tamoxifen enhances NET production in a way unrelated to the estrogen receptor. Further studies linked the tamoxifen effect to its ability to influence neutrophil ceramide levels.

Ref : http://www.nature.com/ncomms/2015/151013/ncomms9369/full/ncomms9369.html