Novel compound holds potential for next-generation prostate cancer treatment

In the search for new ways to attack recurrent prostate cancer, researchers at Duke Health report that a novel compound appears to have a unique way of blocking testosterone from fueling the tumors in mice.

The potential foundation for a next-generation therapy, called tetraaryl cyclobutane, or CB, is being studied as an option for prostate tumors that have grown resistant to current anti-androgen drugs, notably enzalutamide. (see below structure)

"Prostate cancer is the most prevalent form of cancer in men, and the principal driver of tumor growth is the androgen receptor," said John D. Norris, Ph.D., associate research professor in the Department of Pharmacology & Cancer Biology at Duke and senior author of a study published online Aug. 8 in the journal Nature Chemical Biology.

"Suppression of androgen receptor function by anti-endocrine therapies is initially effective, but most tumors develop resistance, resulting in a more aggressive cancer," Norris said. "Our research has been focused on finding a new approach to suppressing androgen receptor activity, because even in situations where tumors are resistant to current therapies, the androgen receptor remains a viable target."

  

Norris and colleagues focused on a group of CB compounds developed in collaboration with scientists at the University of Illinois at Urbana-Champaign. The compounds act as competitive inhibitors of androgen receptors, but are structurally different from current anti-androgens such as enzalutamide.

One of the CB compounds, in particular, inhibits mutant forms of the androgen receptors that promote resistance to enzalutamide. It functions by preventing the androgen receptor from entering the nucleus of the cell where it can promote tumor growth.

"It's encouraging that this compound has a different mechanism of action when compared to current therapies, which gives it a good chance of having efficacy in resistant disease," Norris said. "We have shown in animal models that the compound has activity against prostate tumors where enzalutamide fails."

Norris said additional studies are underway in additional animal models and in tests with other forms of cancer, including breast cancer.

Ref: http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.2131.html#compounds

Novel compound holds potential for next-generation prostate cancer treatment

New drug treatment could reduce body weight in obese patients with rare genetic disorder

As part of a phase II study at Charité - Universitätsmedizin Berlin and the Berlin Institute of Health, two obese patients with a rare genetic disorder were given a drug treatment to stimulate the satiety center in the brain. After only a few weeks, both patients, which were severely hyperphagic before the study start, showed a normalization of their hunger feeling as well as a significant reduction of body weight. Results from this study have been published in the current edition of the New England Journal of Medicine.

Our understanding of the factors involved in the dysregulation of normal body weight remains rudimentary. However it is known that mutations in certain genes play could lead to the development of early onset obesity due to a severe hyperphagia. MC4R is one example; it provides the blueprint for the melanocortin-4 receptor (MC4R) setmelanotide, which regulates energy balance and weight. Activation of the receptor by MSH (melanocyte-stimulating hormone) leads to a reduction in the sensation of hunger. Patients deficient in MSH show severe hyperphagia, and develop obesity within the first months of life.

The study team, led by Dr. Peter Kühnen - a physician at the Institute for Experimental Pediatric Endocrinology -- treated two patients with congenital proopiomelanocortin (POMC) deficiency. POMC is a precursor of the hormone MSH, and is secreted by the hypothalamus; deficiency causes significantly increased hunger. The researchers set out to test whether the new drug might replace the effect of the prohormone through targeted activation of the satiety center. First effects were recorded within a few weeks of the start of treatment. Patient 1, whose starting weight was 155 kg, achieved a total weight loss of 51 kg over a period of 42 weeks; patient 2 (starting weight 152.8 kg) lost a total of 20.5 kg over the course of 12 weeks.

"Our study results confirm the crucial role of the MC4R signaling pathway in appetite regulation, and represent an important contribution to our understanding of the fundamental processes involved in the control of body weight" says Dr. Peter Kühnen. He goes on to add: "It currently remains unclear, however, whether this treatment will be of benefit to patients whose obesity has no clear genetic cause. Further studies will be needed to elucidate this."

Ref : http://www.nejm.org/doi/full/10.1056/NEJMoa1512693

Inosine treatment can help restore motor control after cortical injury

Brain tissue can die as the result of stroke, traumatic brain injury, or neurodegenerative disease. When the affected area includes the motor cortex, impairment of the fine motor control of the hand can result. In a new study published in Restorative Neurology and Neuroscience, researchers found that inosine, a naturally occurring purine nucleoside that is released by cells in response to metabolic stress, can help to restore motor control after brain injury.

Based on evidence from rodent studies, researchers used eight rhesus monkeys ranging in age from 5 to 10 years (approximately equivalent to humans from 15 to 30 years of age). All received medical examinations and motor skills were tested, including video recording of fine motor functions used to retrieve small food rewards. All monkeys were given initial MRI scans to ensure there were no hidden brain abnormalities.

Brain injuries were created in the area controlling each monkey's favored hand. Four monkeys received inosine treatment, while four received a placebo. Research staff were not informed regarding which monkeys were included in the treatment vs placebo groups. Recovery of motor function was then measured for a period of 14 weeks after surgery.

While both the treated and placebo groups recovered significant function, three out of four of the treated monkeys were able to return to their pre-operative grasping methods. The placebo group developed a compensatory grasping method for retrieving food rewards unlike the original thumb-and-finger method.

"In the clinical context, the enhanced recovery of grasp pattern suggests that inosine facilitates greater recovery from this type of cortical injury and motor impairment," explained lead investigator Tara L. Moore, PhD, of the Department of Anatomy & Neurobiology and the Department of Neurology, Boston University School of Medicine, Boston, MA, USA. "To our knowledge, this is the first study to demonstrate the positive effects of inosine for promoting recovery of function following cortical injury in a non-human primate."

Inosine has also been administered in human clinical trials for multiple sclerosis and Parkinson's disease and has been proven to be safe in doses up 3000 mg/day. Athletes have used inosine as a nutritional supplement for decades, and inosine supplements are widely available commercially. "Given the effectiveness of inosine in promoting cortical plasticity, axonal sprouting, and dendritic branching, the present evidence of efficacy after cortical injury in a non-human primate, combined with a long history of safe use, indicates a need for clinical trials with inosine after cortical injury and spinal cord injury," noted Dr. Moore.

The study points to neural plasticity, whereby the brain essentially "re-wires" connections between neurons to reestablish control pathways, as a therapeutic target for the recovery of fine motor control and grasping ability. Further study of cortical tissue from these monkeys is currently being completed and may provide further insights into the mechanisms underlying recovery.

New drug could help decrease symptoms of asthma

"This new drug could be a game changer for future treatment of asthma" - Professor Chris Brightling, NIHR Senior Research Fellow at the University of Leicester.

The first new asthma pill for nearly 20 years has the power to significantly reduce the severity of the condition, a study led by the University of Leicester has found.

The research was funded by Novartis Pharmaceuticals, National Institute for Health Research (NIHR) and the EU (AirPROM), and is described by the lead researcher as "a game changer for future treatment of asthma."

Three people die every day because of asthma attacks and research shows that two thirds of asthma deaths are preventable, according to Asthma UK.

Fevipiprant (QAW039) significantly decreased the symptoms of asthma, improved lung function, reduced inflammation and repaired the lining of airways.

The drug is currently being evaluated in late stage clinical trials for efficacy in patients with severe asthma, according to ClinTrials.gov.

A total of 61 people took part in the research. One group was given 225mg of the drug twice a day for 12 weeks and the other participants were assigned to a placebo group. Fevipiprant and the placebo were added to the medications the participants were already taking.

The study was designed primarily to examine the effects on inflammation in the airway by measuring the sputum eosinophil count.

The sputum eosinophil is an inflammation measurement of a white blood cell that increases in asthma and is used to assess the severity of this condition.

People who do not have asthma have a percentage of less than one and those with moderate-to-severe asthma typically have a reading of about five per cent.

The rate in people with moderate-to-severe asthma taking the medication was reduced from an average of 5.4 percent to 1.1 percent over 12 weeks, according to the study published today in the prestigious The Lancet Respiratory Medicine journal.

Professor Christopher Brightling, who is a NIHR Senior Research Fellow and Clinical Professor in Respiratory Medicine at the University of Leicester, led the study at the NIHR Respiratory Biomedical Research Unit, which is based at the Glenfield Hospital in Leicester.

Professor Brightling said: "A unique feature of this study was how it included measurements of symptoms, lung function using breathing tests, sampling of the airway wall and CT scans of the chest to give a complete picture of how the new drug works.

"Most treatments might improve some of these features of disease, but with Fevipiprant improvements were seen with all of the types of tests.

"We already know that using treatments to target eosinophilic airway inflammation can substantially reduce asthma attacks.

"This new treatment, Fevipiprant, could likewise help to stop preventable asthma attacks, reduce hospital admissions and improve day-to-day symptoms- making it a 'game changer' for future treatment."

Gaye Stokes from Grantham in Lincolnshire has had severe asthma for 16 years. She took part in the trial and was part of the Fevipiprant group.

The 54-year-old said: "I knew straight away that I had been given the drug. I felt like a completely different person. I had more get up and go, I was less wheezy and for the first time in years I felt really, really well.

"For me, it felt like a complete wonder drug and I can't wait for it to be available because I really think it could make a huge difference to me."

After the 12 week trial and Gaye stopped receiving the drug, she said her health started to "go downhill again very quickly".

Professor Brightling added that the latest advance underpinned the work of the Leicester Precision Medicine Institute, a Centre of Excellence that coalesces and aligns the research missions of the University of Leicester and the NHS in Leicester.

Future treatment of human disease will increasingly move from a 'one size fits all' approach to one of tailoring the treatment to the individual patient.

Asthma is a long-term condition that affects the airways. When a person with asthma comes into contact with something that irritates their sensitive airways it causes the body to react in several ways which can include wheezing, coughing and can make breathing more difficult.

The NIHR Leicester Respiratory Biomedical Research Unit - a partnership between the University of Leicester and Leicester's Hospitals - focuses on promoting the development of new and effective therapies for the treatment of respiratory diseases including severe asthma and chronic obstructive pulmonary disease (COPD).

AirPROM stands for 'Airway Disease Predicting Outcomes through Patient Specific Computational Modelling'.

This is the technical name for the five year Europe-wide, EU funded project, which aimed to produce computer and physical models of the whole human airway system for people with asthma and chronic obstructive pulmonary disease (COPD).

AirPROM has demonstrated how an integrated approach, involving modelling, measurement and clinical validation, can accelerate the development of new therapies and improve existing methods.

New drug could help decrease symptoms of asthma

New Antibiotic Discovered in the Nose

German researchers analyzed germs that inhabit the human body and found that about 30 percent of people had Staphylococcus aureus bacteria in their noses, but 70 percent did not, the Associated Press reported.

Those without S. aureus have another type of bacteria -- Staphyloccus lugdunensis -- in the nose that produces an antibiotic that keeps S. aureus in check, according to the study published online in the journal Nature.

Lugdunin is an antibiotic compound, a thiazolidine-containing cyclic peptide. It was isolated in 2016 after Staphylococcus lugdunensis was identified as the species of bacteria from the human nose that suppressed growth of species of disease-causing bacteria in that part of the humanmicrobiome. 

Ludgunin is a non-ribosomally synthesized cyclic peptide that inhibits growth of Staphylococcus aureus strain. The lugdunin genes are located on a 30-kbp operon. The genes lugA, lugB, lugC, and lugD encode four non-ribosomal peptide synthases, which are preceded by a putative regulator gene lugR

The scientists isolated this antibiotic, which they call lugdunin, and found that it was effective in treating mice whose skin was infected with S. aureus, the AP reported.

Lugdunin may offer a new way to fight antibiotic-resistant staph bacteria, one of the superbugs that pose a major health threat worldwide. Tests of lugdunin in humans have yet to be conducted.

FDA Approves First Generic Version of Widely Used Influenza Drug Tamiflu

In continuation of my update on tamiflu oseltamivir phosphate

U.S. Food and Drug Administration approved the first generic version of Tamiflu (oseltamivir phosphate), a widely used medication for the treatment of the flu (influenza A and B) in patients two weeks of age and older who have had flu symptoms for no more than 48 hours; and prevention of the flu in patients one year of age and older. Tamiflu was approved in 1999.

The FDA is committed to improving patient access to safe and effective generic drugs. Generic drugs approved by the FDA have the same high-quality and strength as brand-name drugs. The generic manufacturing and packaging sites must pass the same quality standards as those of brand-name drugs.

The most common side effects reported by people using oseltamivir phosphate in clinical trials included nausea and vomiting.

Patients must use oseltamivir phosphate as directed by their health care provider. Oseltamivir phosphate does not take the place of receiving a flu vaccination. Talk to your health care provider about when you should receive an annual flu vaccination.

Oseltamivir phosphate does not treat or prevent illness caused by infections other than the influenza virus, and oseltamivir phosphate does not prevent bacterial infections that may happen with the flu. The FDA does not know if oseltamivir phosphate is effective in people who start treatment after two days of developing symptoms, or have weakened immune systems.

Patients and health care providers may find more information on oseltamivir phosphate in the drug label.

FDA Approves Flonase Sensimist Allergy Relief

In continuation of my update on fluticasone

GSK Consumer Healthcare announced today that the U.S. Food and Drug Administration (FDA) has approved Flonase® Sensimist™ Allergy Relief (fluticasone furoate, 27.5 mcg spray) as an over-the-counter (OTC) treatment for symptoms associated with seasonal and perennial allergies. Previously available by prescription as Veramyst®, Flonase Sensimist is the latest Rx-to-OTC switch from GSK.

Flonase Sensimist helps block six allergic substances*, providing non-drowsy, 24-hour relief of both nose- and eye-related allergy symptoms like itchy, watery eyes**, nasal congestion, runny nose, itchy nose and sneezing.

“There are roughly 50 million people in the United States who suffer from allergies,2 and, as a category leader, GSK continues to innovate to satisfy the needs of all allergy sufferers,” said Amardeep Kahlon, Director of Marketing. “In the case of Flonase Sensimist, GSK is proud to offer an additional treatment option that not only provides more complete allergy symptom relief1 but also suits specific consumer preferences.”

Additional key features of Flonase Sensimist include:

• Nasal allergy relief indicated for adults and children ages 2 and older**
• Scent-free
• Alcohol-free
• Little or no drip

Flonase Sensimist will be nationally available OTC in early 2017.

About Flonase Sensimist

Flonase Sensimist (fluticasone furoate, 27.5 mcg spray) is an approved over-the-counter treatment for symptoms associated with seasonal and perennial allergic rhinitis including sneezing, runny nose, itchy nose, congestion, and itchy, watery eyes.**

FDA Approves Flonase Sensimist Allergy Relief

FDA Approves Qbrelis (lisinopril) Oral Solution for Pediatric Patients 6 Years of Age and Older

We know that,  Lisinopril is a drug of the angiotensin-converting enzyme (ACE) inhibitor class used primarily in treatment of high blood pressure, heart failure, and after heart attacks. It is also used for preventing kidney and eye complications in people with diabetes. Its indications,contraindications, and side effects are as those for all ACE inhibitors.

Lisinopril was the third ACE inhibitor (after captopril and enalapril) and was introduced into therapy in the early 1990s. A number of properties distinguish it from other ACE inhibitors: It ishydrophilic, has a long half-life and tissue penetration, and is not metabolized by the liver.

Now Silvergate Pharmaceuticals, Inc., leader in the development and commercialization of innovative and safe medicines for children, today announced that the United States Food and Drug Administration (FDA) approved Qbrelis (Lisinopril) Oral Solution, the first and only FDA-approved Lisinopril oral solution. Qbrelis is indicated for the treatment of hypertension (high blood pressure) in adult patients and pediatric patients 6 years of age and older, adjunct therapy for heart failure, and treatment of acute myocardial infarction in adults. 

“We are excited to launch our second product focused on pediatric patients and pediatric hypertension” said Frank Segrave, President & CEO, Silvergate Pharmaceuticals, Inc. “Qbrelis provides a ready-to-use oral solution for these children with the additional assurance of an FDA approved medication. As a company, we continue to focus on pediatric medications that are safe, effective, and readily available.”

Qbrelis enables weight-based dosing for children 6 years of age and older who until now have relied on an adjusted adult dose. Qbrelis will be available through an extensive network of pharmacies and a qualified mail order service. For additional information on how to obtain Qbrelis, please call 1-855-379-0382.

About Qbrelis

Qbrelis delivers the trusted efficacy of lisinopril (an ACE inhibitor), the effectiveness of which has been well established in clinical trials.1 As a unique formulation of an oral solution, Qbrelis provides consistent potency and stability in each dose1, in addition to the quality of a product made in accordance with FDA regulations and requirements. People who have trouble swallowing lisinopril tablets may also benefit from Qbrelis.

Qbrelis reduces blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Control of high blood pressure should be part of a comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.

More info @ https://www.drugs.com/history/qbrelis.html

Lisinopril oral solution approved for treatment of hypertension in children and adults

Silvergate Pharmaceuticals, Inc.  leader in the development and commercialization of innovative and safe medicines for children, today announced that the United States Food and Drug Administration (FDA) approved Qbrelis™ (Lisinopril) Oral Solution, the first and only FDA-approved Lisinopril oral solution. Qbrelis™ is indicated for the treatment of hypertension (high blood pressure) in adult patients and pediatric patients 6 years of age and older, adjunct therapy for heart failure, and treatment of acute myocardial infarction in adults.

"We are excited to launch our second product focused on pediatric patients and pediatric hypertension" said Frank Segrave, President & CEO, Silvergate Pharmaceuticals, Inc. "Qbrelis provides a ready-to-use oral solution for these children with the additional assurance of an FDA approved medication. As a company, we continue to focus on pediatric medications that are safe, effective, and readily available."

Qbrelis enables weight-based dosing for children 6 years of age and older who until now have relied on an adjusted adult dose. Qbrelis will be available through an extensive network of pharmacies and a qualified mail order service.

Lisinopril oral solution approved for treatment of hypertension in children and adults

Silvergate Pharmaceuticals, Inc.  leader in the development and commercialization of innovative and safe medicines for children, today announced that the United States Food and Drug Administration (FDA) approved Qbrelis™ (Lisinopril) Oral Solution, the first and only FDA-approved Lisinopril oral solution. Qbrelis™ is indicated for the treatment of hypertension (high blood pressure) in adult patients and pediatric patients 6 years of age and older, adjunct therapy for heart failure, and treatment of acute myocardial infarction in adults.

"We are excited to launch our second product focused on pediatric patients and pediatric hypertension" said Frank Segrave, President & CEO, Silvergate Pharmaceuticals, Inc. "Qbrelis provides a ready-to-use oral solution for these children with the additional assurance of an FDA approved medication. As a company, we continue to focus on pediatric medications that are safe, effective, and readily available."

Qbrelis enables weight-based dosing for children 6 years of age and older who until now have relied on an adjusted adult dose. Qbrelis will be available through an extensive network of pharmacies and a qualified mail order service.