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.

Drug compounds target multiple pathways associated with myotonic dystrophy type 1

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

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).

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

New protein supplement lowers cholesterol, prevents osteoporosis

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.

New protein supplement lowers cholesterol, prevents osteoporosis

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

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%).

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

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

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.

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

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."

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

Dementia drug 'keeps patients out of nursing homes'

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

Dementia drug 'keeps patients out of nursing homes'  

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

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.

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

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.

Lithium chloride could offer effective treatment against osteoarthritis

Praziquantel treatment safe for pregnant women after first trimester

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."

Praziquantel treatment safe for pregnant women after first trimester

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

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

Early trial results in lung cancer

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.

Early trial results in lung cancer

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

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."

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

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.

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

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."

Cranberry juice consumption may protect against cardiovascular disease