FDA Approves Brintellix to Treat Major Depressive Disorder

We know that, Vortioxetine (vor-tye-ox-e-teen, trade name Brintellix, previously known as Lu AA21004) is a novel atypical antidepressant made byLundbeck and Takeda. On September 30, 2013, it was approved approved by the U.S. FDA for the treatment of major depressive disorder (MDD) in adults.  Vortioxetine was also investigated as a treatment for generalized anxiety disorder (GAD).

Regulatory approval for the treatment of MDD for the European market has been filed in September 2012, for the United States in October 2012, and filing for Canada should follow. Filing for the Japanese market is expected in 2013.

The U.S. Food and Drug Administration recently approved Brintellix (vortioxetine) to treat adults with major depressive disorder.

FDA Approves Brintellix to Treat Major Depressive Disorder

FDA Approves Duavee to Treat Hot Flashes and Prevent Osteoporosis

Bazedoxifene is a third generation selective estrogen receptor modulator (SERM), under development by Pfizer following the completion of their takeover of Wyeth Pharmaceuticals. Pfizer are seeking approval for bazedoxifene in the prevention and treatment ofpostmenopausal osteoporosis. Bazedoxfiene is the result of an exclusive research collaboration between Wyeth Pharmaceuticalsand Ligand Pharmaceuticals.

The U.S. Food and Drug Administration today approved Duavee (conjugated estrogens/bazedoxifene) for women who suffer from moderate-to-severe hot flashes (vasomotor symptoms) associated with menopause and to prevent osteoporosis after menopause....

FDA Approves Duavee to Treat Hot Flashes and Prevent Osteoporosis

Apple impregnated with tangerine juice reduces risk of cardiovascular disease in obese children

Apple impregnated with tangerine juice reduces risk of cardiovascular disease in obese children

"It is not a product that induces weight loss in children, but it would help improve their quality of life. The modification of oxidative stress in adipose tissue (or fat tissue) can help in the prevention of cardiovascular risk associated with childhood obesity and in the long term prevent diseases such as atherosclerosis (hardening and narrowing of the arteries caused by the accumulation of fat, cholesterol and other substances)," said Dr. Pilar Codoñer, head of the Department of Paediatrics, University Hospital Doctor Peset and professor in the Department of Paediatrics at the Universitat de València.

To obtain the snack, researchers enriched apple slices with mandarin juice using a technology of impregnation developed and patented by the UPV team that allows incorporating additional ingredients to the structure of porous foods, as in the case of fruits and vegetables.

"After several years of work the product is ready to be marketed by private companies. Our snack has all the properties of two products as healthy as apples and tangerine and has no added ingredient. It is an alternative to snacks that exist in the market that contain oils and saturated fats and therefore are high in calories," says Noelia Betoret, principal researcher and professor at the School of Agricultural Engineering and Natural Environment.

Ref : https://webges.uv.es/public/uvRecullWeb/2013/09/20130924_19787.jpg

New class of antidepressants appears potentially effective in combating deadly form of lung cancer

Jahchan tested the effect of a tricyclic antidepressant called imipramine  (see structure)  on human small-cell lung cancer cells grown in the laboratory and growing as tumors in laboratory mice. She found that the drug was able to potently activate a self-destruction pathway in the cancer cells and to slow or block metastases in the animals. The drug maintained its effectiveness regardless of whether the cancer cells had previously been exposed, and become resistant, to traditional chemotherapy treatments. Another drug, an antihistamine called promethazine, identified by the bioinformatics screen, also exhibited cancer-cell-killing abilities.

Although imipramine did not affect cells from another main type of lung cancer called non-small-cell lung adenocarcinoma, it did inhibit the growth of cells from other neuroendocrine tumors, including pancreatic neuroendocrine cancers, an aggressive skin cancer called Merkel cell carcinoma, and a pediatric cancer called neuroblastoma. (Neuroendocrine cells receive signals from the nervous system and secrete hormoneslike adrenaline into the blood to affect the body's function.)

Further investigation showed that the drugs appear to work through a class of molecule on the cancer cells' surfaces called G-protein-coupled receptors, but the researchers are continuing to investigate exactly how the drugs specifically kill neuroendocrine cancer cells.

"Our collaboration with the Butte lab allowed us to move very quickly from the initial idea to very convincing results," Sage said. "It was less than 20 months from the time of our first discussion to a clinical trial because the bioinformatics approach had been established and the drugs are FDA-approved. By focusing on diseases with little hope for the patient, it's easier to go forward fast."

Ref : http://cancerdiscovery.aacrjournals.org/content/early/2013/09/16/2159-8290.CD-13-0183.abstract

New class of antidepressants appears potentially effective in combating deadly form of lung cancer

Addition of walnuts to diet can protect against diabetes and heart disease in at-risk individuals

Addition of walnuts to diet can protect against diabetes and heart disease in at-risk individuals

The research found that daily intake of 56g of walnuts improves endothelial function in overweight adults with visceral adiposity. The addition of walnuts to the diet does not lead to weight gain. Further study on the topic is still suggested. "The primary outcome measure was the change in flow-mediated vasodilatation (FMD) of the brachial artery," wrote the research group. "Secondary measures included serum lipid panel, fasting glucose and insulin, Homeostasis Model Assessment-Insulin Resistance values, blood pressure, and anthropometric measures. FMD improved significantly from baseline when subjects consumed a walnut-enriched diet as compared with the control diet. Beneficial trends in systolic blood pressure reduction were seen, and maintenance of the baseline anthropometric values was also observed. Other measures were unaltered."

Ref : http://www.tandfonline.com/doi/full/10.1080/07315724.2012.10720468#.UkFcg4ZkPng

Apple impregnated with tangerine juice reduces risk of cardiovascular disease in obese children

Apple impregnated with tangerine juice reduces risk of cardiovascular disease in obese children

"It is not a product that induces weight loss in children, but it would help improve their quality of life. The modification of oxidative stress in adipose tissue (or fat tissue) can help in the prevention of cardiovascular risk associated with childhood obesity and in the long term prevent diseases such as atherosclerosis (hardening and narrowing of the arteries caused by the accumulation of fat, cholesterol and other substances)," said Dr. Pilar Codoñer, head of the Department of Paediatrics, University Hospital Doctor Peset and professor in the Department of Paediatrics at the Universitat de València.

To obtain the snack, researchers enriched apple slices with mandarin juice using a technology of impregnation developed and patented by the UPV team that allows incorporating additional ingredients to the structure of porous foods, as in the case of fruits and vegetables.

"After several years of work the product is ready to be marketed by private companies. Our snack has all the properties of two products as healthy as apples and tangerine and has no added ingredient. It is an alternative to snacks that exist in the market that contain oils and saturated fats and therefore are high in calories," says Noelia Betoret, principal researcher and professor at the School of Agricultural Engineering and Natural Environment.

Ref : https://webges.uv.es/public/uvRecullWeb/2013/09/20130924_19787.jpg

Cisplatin plus radiotherapy and HDRB proves beneficial in stage IIIB cervical cancer

In continuation of my update on cis-platin

Cisplatin plus radiotherapy and HDRB proves beneficial in stage IIIB cervical cancer

Phase III EINSTEIN trial program: XARELTO reduces risk of DVT and PE

In continuation of my update on Rivaroxaban

The EINSTEIN-PE study was an open-label, randomized, non-inferiority trial. The trial compared oral rivaroxaban – 15 mg twice daily for three weeks, followed by 20 mg once daily – with the current standard of care (enoxaparin followed by a Vitamin K Antagonist [VKA]) in subjects with acute symptomatic PE with or without symptomatic DVT. Patients received treatment for six or 12 months. EINSTEIN-PE enrolled 4,833 participants and is the largest study ever conducted in the acute treatment of PE. 

Read more...

Phase III EINSTEIN trial program: XARELTO reduces risk of DVT and PE

Alefacept drug shows encouraging results in phase 2 trial for type 1 diabetes

Alefacept drug shows encouraging results in phase 2 trial for type 1 diabetes

Cell death protein could offer new anti-inflammatory drug target

Scientists in Melbourne, Australia, have revealed the structure of a protein that is essential for triggering a form of programmed cell death called necroptosis, making possible the development of new drugs to treat chronic inflammatory diseases such as Crohn's disease and rheumatoid arthritis.

Ref : http://dx.doi.org/10.1016/j.immuni.2013.06.018

Cell death protein could offer new anti-inflammatory drug target

Drug blocks light sensors in eye that may trigger migraine attacks

Panda and his collaborators turned to the Lundbeck library of diverse compounds. In hundreds of 384-well plates, a team led by Ken Jones at Lundbeck tested whether each chemical from the library turned off melanopsin by measuring the calcium levels after the plate was exposed to light. When melanopsin is functioning, calcium levels increase after light exposure indicating that light has been sensed and a signal is being generated. Several compounds from the chemical library stopped this calcium increase from happening, suggesting that they were blocking the function of melanopsin.

None of these compounds looked like retinoids, so it was an exciting breakthrough, Panda says. The chemicals, dubbed opsinamides (see structures a few), also 

showed no interaction with rhodopsin or other opsins. "We wanted to make sure they were specific to melanopsin," says Panda. To find out whether the opsinamides would have a physiological response in addition to binding to melanopsin in bench experiments, Megumi Hatori and Ludovic Mure from Panda's Salk lab group next looked at whether the drug affected the pupillary constriction in mice. Normally, in extremely bright light, the pupil of the eye shrinks to its smallest size. But when the mice were treated with one of the opsinamides, their pupils didn't shrink as usual. Most importantly, the drug had no detectable effect in mice lacking melanopsin, further showing its specificity for melanopsin. Finally, newborn mice treated with the compound no longer avoided bright lights. The results, Panda says, show that the drug is stopping melanopsin from signaling the brain when the eyes are exposed to bright light.

"So far, everything known about melanopsin has been discovered using knock-out mice that completely lack the receptor," says Panda. "So this offers a new way to study the protein." Kenneth Jones, the former project head at Lundbeck, notes that "the two compounds require further optimization in anticipation of clinical testing but are extraordinarily useful for research purposes and as leads in the discovery process." Co-author Jeffrey Sprouse has co-founded a start-up company, Cyanaptic, to do just that...

Ref : http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.1333.html#figures

Drug blocks light sensors in eye that may trigger migraine attacks

Investigational oral regimen for hepatitis C shows promise

In a study of an all-oral drug regimen, a majority of volunteers with liver damage due to hepatitis C virus (HCV) infection were cured following a six-month course of therapy that combined an experimental drug, sofosbuvir, with the licensed antiviral drug ribavirin. The results showed that the regimen was highly effective in clearing the virus and well tolerated in a group of patients who historically have had unfavorable prognoses.

Investigational oral regimen for hepatitis C shows promise

Promising chronic pain drug developed

4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanol benzofuro[3,2-e]isoquinoline-7(7aH)-one (UMB 425)

Spotlighted in a recent issue of ACS Chemical Neuroscience, the compound, known as UMB 425, is as strong as morphine, but displays diminished tolerance over time with no obvious toxic effects.

"UMB 425 is a breakthrough in the development of therapeutics to treat chronic pain," says Coop. "Unlike other drugs developed to act on only one biological target, UMB 425 acts on two different opioid receptors in the body. When activated at the same time, these receptors work together to provide pain relief and slow the body's development of tolerance to the drug. This diminished tolerance allows a lower dose of the opioid to be administered for a longer time period, while still achieving the same level of pain relief."

For individuals living with chronic pain, either as a result of injury or disease such as arthritis, opioids are the standard treatment. But as the dosage increases to offset the body's tolerance to their effects, opioids cause a number of adverse effects, including constipation, nausea, drowsiness, and dizziness. The unique dual-profile of UMB 425 -- made possible through Coop's collaborations with Alexander MacKerell, PhD, professor in PSC and director of the School's Computer Aided Drug Design Center, and Maureen Kane, PhD, assistant professor in PSC and co-director of the School's Mass Spectrometry Facility -- provides both pain relief as well as diminished tolerance in one drug.

"Historically, medicinal chemists have developed drugs aimed at only one biological target," says Coop. "However, two drugs administered together have the potential to metabolize differently in different individuals, as well as affect patients' adherence to both drugs. A single compound that is able to provide both pain relief and diminished tolerance has the advantage of a defined ratio that we can optimize to ensure patients receive the maximum pain relief, while experiencing minimum adverse effects."

Ref : http://pubs.acs.org/doi/pdf/10.1021/cn4000428

Promising chronic pain drug developed

Eating whole fruits linked to lower risk of Type 2 diabetes

Eating more whole fruits, particularly blueberries, grapes, and apples, was significantly associated with a lower risk of type 2 diabetes, according to a new study led by Harvard School of Public Health (HSPH) researchers. Greater consumption of fruit juices was associated with a higher risk of type 2 diabetes. The study is the first to look at the effects of individual fruits on diabetes risk.

Eating whole fruits linked to lower risk of Type 2 diabetes

Unexpected use of former cancer drug, Zebularine...

Researchers at Lund University have unexpectedly discovered that an old cancer drug can be used to prevent rejection of transplanted tissue. The researchers now have high hopes that their discovery could lead to new treatments for both transplant patients and patients with autoimmune diseases.

"Our group were studying the effects of the old tumour drug Zebularine, (see structure) developed in the USA in the 1960s, and by chance we discovered that it had completely unexpected effects on the immune system," says Leif Salford, Senior Professor of Neurosurgery.

"It turned out that Zebularine has the ability to subdue the reaction of the body's immune system. This could be important in situations where tissue or organs are transplanted. We also think it could be used to curb the body's attacks on its own tissue in autoimmune diseases, for instance type 1 diabetes or rheumatoid arthritis," says Dr Nittby.

In studies on animals, the researchers used rats that were made diabetic. The researchers transplanted the islets of Langerhans  cell groups in the pancreas producing insulin -- from healthy rats from another kind of rat into those with diabetes. The diabetic rats were divided into two groups; one group were treated with Zebularine and the other, the control group, did not receive any treatment. The diabetic rats that were treated with Zebularine survived for a significantly longer period than the untreated rats.

"It is very interesting that we only treated them with Zebularine for two weeks, but the effects of the treatment could be observed throughout the 90-day follow-up period.

"The findings are very exciting and are a sign that the immune system was not just generally suppressed, but that the treatment was more targeted. Neither did we see any signs of side-effects," said Dr Nittby.

The researchers are now working intensively to further refine the treatment. The next step is to teach certain cells in the immune system -- the dendritic cells -- to accept certain specific proteins using the Zebularine treatment. This would mean that the treatment could be targeted even more.

Unexpected use of former cancer drug