Walnuts may help prevent Alzheimer's disease, study finds

Animal study reveals potential brain-health benefits of a walnut-enriched diet. A new animal study published in the Journal of Alzheimer's Disease indicates that a diet including walnuts may have a beneficial effect in reducing the risk, delaying the onset, slowing the progression of, or preventing Alzheimer's disease.

Research led by Abha Chauhan, PhD, head of the Developmental Neuroscience Laboratory at the New York State Institute for Basic Research in Developmental Disabilities (IBR), found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet.

The researchers suggest that the high antioxidant content of walnuts (3.7 mmol/ounce) may have been a contributing factor in protecting the mouse brain from the degeneration typically seen in Alzheimer's disease. Oxidative stress and inflammation are prominent features in this disease, which affects more than five million Americans.

More : http://www.j-alz.com/node/396

Walnuts may help prevent Alzheimer's disease, study finds

Afatinib active against NSCLC nervous system metastases

Incontinuation of my update on Afatinib

Afatinib active against NSCLC nervous system metastases

Nanoparticle-based invention moves new drugs closer to clinical testing

Penn State College of Medicine researchers have developed a nanoparticle to deliver a melanoma-fighting drug directly to the cancer.

Delivering cancer drugs directly to tumors is difficult. Scientists are working on new approaches to overcome the natural limitations of drugs, including loading them into nanoparticles.

"The drug is packaged into a lipid ball significantly smaller than the width of a hair to make it soluble in the blood stream and prevent negative side effects. The drug-containing nanoparticle ball then travels in the bloodstream to the tumor, where it accumulates and the drug is released in the tumor to kill the cancer cells," said Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery and director of the Penn State Hershey Melanoma Center.

In previous research, Robertson discovered the cancer-fighting characteristics of leelamine, a substance derived from pine bark. But leelamine cannot be given by mouth because of poor uptake in the gastrointestinal tract or be injected intravenously because it causes damage to red blood cells.

To address this issue, Robertson and his team developed a new nanoliposome that loads leelamine, called Nanolipolee-007. Nanolipolee-007 can be injected intravenously without causing damage to red blood cells. It then accumulates in tumors because of its small size where it releases the drug to kill the cancer cells.

Leelamine is the first of a new unique class of drugs that inhibits cholesterol movement around a cancer cell to shut down signals needed for cancer cell survival. As a result, protein pathways like the PI3K, MAPK and STAT3 that are highly active and help cancer cells multiply and spread, are turned off and the cancer cells die. Since normal cells are not addicted to the high levels of activity of these pathways that occur in cancer cells, the drug has a minor effect on them.

"This nanoparticle moves leelamine one step closer to the clinic," Robertson said. "We now have a drug that has the potential to be given to humans that could not be done before."

The researchers showed the results of Nanolipolee-007 on cells growing in culture dishes and in tumors growing in mice following intravenous injection. Leelamine inhibited tumor development in mice with no detectable side effects.

Nanoparticle-based invention moves new drugs closer to clinical testing  

VAL-083 drug compound shows promise against non-small cell lung cancer

We know that, VAL-083 is a bi-functional alkylating agent; inhibit U251 and SF188 cell growth in monolayer better than TMZ and caused apoptosis.

DelMar Pharmaceuticals, Inc., (OTCQB: DMPI), a clinical-stage oncology company, today announced the presentation of promising new data supporting the activity of its lead drug compound, VAL-083, in the treatment of non-small cell lung cancer (NSCLC) at the AACR's New Horizons in Cancer Research: Harnessing Breakthroughs – Targeting Cures. The conference takes place October 9th to 12th in Pudong, Shanghai.

"The data presented today showed that VAL-083 is superior to cisplatin in both tumor models that are sensitive and resistant to tyrosine kinase inhibitors and has synergistic effect in combination with cisplatin," said Jeffrey Bacha, president and CEO of DelMar Pharmaceuticals. "This data suggests important clinical and market potential of VAL-083 in non-small cell lung cancer."

DelMar's lead clinical compound, VAL-083 (dianhydrogalactitol) is a first-in-class alkylating agent with a novel cytotoxic mechanism distinct from other alkylating agents used in the treatment of cancer.

In historical studies sponsored by the National Cancer Institute in the United States, VAL-083 exhibited clinical activity against a range of tumor types including CNS tumors, solid tumors and hematologic malignancies. VAL-083 is approved in China for the treatment ofchronic myelogenous leukemia (CML) and lung cancer (Approval No. Guoyao Zhunzi H45021133; manufactured by Guangxi Wuzhou Pharmaceutical (Group) Co. Ltd.)

NSCLC is usually treated with either tyrosine kinase inhibitors (TKIs) (e.g. gefitinib) or platinum-based regimens (e.g. cisplatin). TKIs have resulted in vastly improved outcomes for patients with EGFR mutations; however, TKI resistance has emerged as a significant unmet medical need, and long-term prognosis with platinum-based therapies is poor. Compared to other countries, Asian patients with NSCLC have a higher incidence of EGFR mutations (up to 60 percent; compared to 10-20 percent in Western populations) and are more susceptible to TKI resistance.

Additionally, NSCLC patients have a high incidence of brain metastases, which is associated with a poor prognosis. The median overall survival time for patients with stage IV NSCLC is four months, while one-year and five-year survival is less than 16 percent and 2 percent, respectively. VAL-083 can cross the blood-brain barrier and is currently being evaluated in the United States in a Phase 1/2 clinical trial to treat the most common form of brain cancer, glioblastoma multiforme (GBM).

 

VAL-083 drug compound shows promise against non-small cell lung cancer

Synthetic oil triheptanoin improves Rett syndrome, longevity

We know that, Triheptanoin is a triglyceride that is composed of three seven-carbon fatty acids. These odd-carbon fatty acids are able to provide anaplerotic substrates for the TCA cycle. Triheptanoin is used clinically in humans to treat inherited metabolic diseases, such aspyruvate carboxylase deficiency and carnitine palmitoyltransferase II deficiency. It also appears to increase the efficacy of the ketogenic diet as a treatment for epilepsy.

Now the research team used mice lacking the MeCP2 protein, which left them with severe Rett syndrome. In examining those mice, what stood out, according to Gabriele Ronnett, M.D., Ph.D., who led the research project at the Johns Hopkins University School of Medicine, was that they weighed the same as healthy mice but had large fat deposits accompanied by lower amounts of nonfat tissue, such as muscle. This suggested that calories were not being used to support normal tissue function but instead were being stored as fat.

This possibility led Ronnett and her research team to consider the role of mitochondria, which transform the building blocks of nutrients into a high-energy molecule, ATP. This molecule drives processes such as the building of muscle and the growth of nerve cells. Mitochondria use a series of biochemical reactions, collectively called the TCA cycle, to make this transformation possible. According to Susan Aja, Ph.D., a research associate and lead member of the research team, "If the components of the TCA cycle are low, nutrient building blocks are not processed well to create ATP. They are instead stored as fat."

Synthetic oil triheptanoin improves Rett syndrome, longevity

Akynzeo Approved for Side Effects of Chemotherapy

The combination drug Akynzeo [netupitant (left) and palonosetron (right)] has been approved by the U.S. Food and Drug Administration to treat nausea and vomiting among people undergoing chemotherapy, the agency said Friday in a news release.

Akynzeo contains a new anti-nausea drug, netupitant, and palonosetron, which was approved to treat nausea and vomiting in 2008.

The combination drug's effectiveness was evaluated in two clinical studies involving 1,720 people. The trials established that Akynzeo was more effective in preventing nausea and vomiting than palonosetron taken alone, the FDA said.

The most frequent side effects of the combination drug included headache, weakness, fatigue, indigestion and constipation.

Akynzeo is marketed and distributed by Eisai Inc. of Woodcliff Lake, N.J., under license from Switzerland-based Helsinn Healthcare.

Akynzeo Approved for Side Effects of Chemotherapy 

Harvoni Approved for Chronic Hepatitis C

In continuation of my update on  ledipasvir and sofosbuvir (Harvoni-combination pill) 

Harvoni, a daily pill that treats the most common form of hepatitis C, was approved by the U.S. Food and Drug Administration on Friday.

It's the first combination pill (ledipasvir and sofosbuvir) approved to treat the chronic infection, and the first medication that doesn't require that the antiviral drugs interferon or ribavirin be taken at the same time, the FDA said in a news release.

Both drugs in the combination pill interfere with the hepatitis C virus' ability to multiply. One of the drugs, sofosbuvir (Sovaldi) was approved in December 2013, while ledipasvir is a new antiviral, the agency said.

"With the development and approval of new treatments for hepatitis C virus, we are changing the treatment paradigm for Americans living with the disease," Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in the news release. "Until last year, the only available treatments for hepatitis C virus required administration with interferon and ribavirin. Now, patients and health care professionals have multiple treatment options, including a combination pill to help simplify treatment regimens."

One expert applauded Harvoni's approval.

"This is a giant step forward for people with [hepatitis C]. One pill, once daily, no interferon, no ribavirin and 94 to 99 percent cure! It moves the risk-benefit ratio needle way over toward benefit," said Dr. Douglas Dieterich, a professor of medicine in the division of liver diseases at The Mount Sinai Hospital in New York City.

However, price has been an issue with some of the new treatments for hepatitis C. For example, Sovaldi alone costs $1,000 a day and not all insurance companies cover the cost of treatment, experts have noted. Harvoni will cost $1,125 a pill, the Associated Press reported Friday.

Hepatitis C causes inflammation of the liver, which could spark other problems including diminished liver function (cirrhosis), scarring, liver cancer or liver failure. Most infected people aren't aware that they carry the virus until liver damage has occurred, the agency said.

Some 3.2 million Americans are believed to be infected with hepatitis C, the FDA said.

Harvoni was evaluated in three clinical studies involving more than 1,500 people who either hadn't been treated previously or hadn't responded to prior treatment. The most common side effects were fatigue and headache.

Harvoni Approved for Chronic Hepatitis C  

Impotence Drug Might Counter Common Gene Mutation in Type 2 Diabetes

In a small study, Swedish researchers found that the impotence drug yohimbine might help people with type 2 diabetes who have a particular gene mutation that lowers their insulin production.

Among 50 men and women with type 2 diabetes partially caused by a mutation in a gene called alpha(2A)-AR, those treated with yohimbine showed improved insulin production and lower blood sugar levels, compared with those receiving a placebo.

"If a diabetic patient carries the risk mutation, he or she is more sensitive to stress hormones such as adrenaline," said lead researcher Dr. Anders Rosengren, head of the translational diabetes research group at Lund University Diabetes Center in Malmo.

About 40 percent of patients with type 2 diabetes carry this mutation. "It is not that patients are more stressed, but that adrenaline suppresses insulin secretion," he added.

Rosengren explained how the drug overcomes the effects of the mutation: "It is like driving a car with the brakes constantly on. If you add yohimbine, you release the brake and the car -- the insulin-producing cells -- can go at normal speed. The cells secrete adequate amounts of insulin in response to sugar."

Impotence Drug Might Counter Common Gene Mutation in Type 2 Diabetes: Study 

FDA Approves Uceris (budesonide) Rectal Foam for Ulcerative Colitis

In continuation of my update on budesonide

Salix Pharmaceuticals, Ltd. announced that the Food and Drug Administration (FDA) has granted final approval for Uceris (budesonide) rectal foam for the induction of remission in patients with active mild-to-moderate distal ulcerative colitis (UC) extending up to 40cm from the anal verge. The foam is a rectally administered corticosteroid that overcomes treatment limitations associated with currently approved therapies which are often ineffective due to insufficient distribution of active drug to the distal colon. On September 15, 2014 the FDA tentatively approved Uceris rectal foam pending expiration of the 45-day waiting period described in section 505( c )(3)( C ) of the Federal Food, Drug and Cosmetic Act. The waiting period has expired and the FDA has granted Uceris rectal foam final approval as of October 7, 2014.

FDA Approves Uceris (budesonide) Rectal Foam for Ulcerative Colitis

Attacking type 2 diabetes from a new direction with encouraging results

Type 2 diabetes affects  an estimated   28  million  Americans  according  to  the  American  Diabetes association, but medications now  available  only  treat  symptoms,  not  the root  cause of the disease.    New research from Rutgers shows promising evidence that     a  modified form of a different drug, niclosamide     now used to eliminate    intestinal parasites   may       hold the key to battling the disease at its source.

Ref : http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3699.html

Attacking type 2 diabetes from a new direction with encouraging results  

First pictures of BRCA2 protein show how it works to repair DNA

In continuation of my update on BRCA2 

Scientists have taken pictures of the BRCA2 protein for the first time, showing how it works to repair damaged DNA. The findings showed that each pair of BRCA2 proteins binds two sets of RAD51 that run in opposite directions. This allows it to work on strands of broken DNA that point in either direction. They also show that BRCA2's job is to help RAD51 form short filaments at multiple sites along the DNA, presumably to increase the efficiency of establishing longer filaments required to search for matching strands.

Researchers at Imperial College London and the Cancer Research UK London Research Institute purified the protein and used electron microscopy to reveal its structure and how it interacts with other proteins and DNA. The results are published today in Nature Structural and Molecular Biology.

Around one in 1000 people in the UK have a mutation in the BRCA2 gene. The lifetime risk of breast cancer for women with BRCA2 mutations is 40 to 85 per cent, depending on the mutation, compared with around 12 per cent for the general population. Many women who test positive for BRCA1 and BRCA2 mutations choose to undergo surgery to reduce their risk of breast cancer. Mutations can also raise the risk of other cancers, such as ovarian, prostate and pancreatic cancer.

The BRCA1 and BRCA2 genes encode proteins involved in DNA repair. The DNA in our cells undergoes damage thousands of times a day, caused by toxic chemicals, metabolic by-products and ultraviolet radiation. Repair mechanisms correct most of this damage, but unrepaired damage can lead to cancer.

The study was led by Professor Xiaodong Zhang from the Department of Medicine at Imperial College London and Dr Stephen West at the London Research Institute.

"This study improves our understanding of a fundamental cause of cancer," said Professor Zhang, a Wellcome Trust Senior Investigator. "It's our first view of how the protein looks and how it works, and it gives us a platform to design new experiments to probe its mechanism in greater detail.

"Once we have added more detail to the picture, we can design ways to correct defects in BRCA2 and help cells repair DNA more effectively to prevent cancer. We can also think about how to make the repair process less effective in cancer cells, so that they die."

The study found that BRCA2 proteins work in pairs -- which the researchers found surprising since BRCA2 is one of the largest proteins in the cell.

BRCA2 works in partnership with another protein called RAD51. BRCA2 helps RAD51 molecules to assemble on strands of broken DNA and form filaments. The RAD51 filaments then search for matching strands of DNA in order to repair the break.

The findings showed that each pair of BRCA2 proteins binds two sets of RAD51 that run in opposite directions. This allows it to work on strands of broken DNA that point in either direction. They also show that BRCA2's job is to help RAD51 form short filaments at multiple sites along the DNA, presumably to increase the efficiency of establishing longer filaments required to search for matching strands.

Ref : http://dx.doi.org/10.1038/nsmb.2899

First pictures of BRCA2 protein show how it works to repair DNA  

'Programmable' antibiotic harnesses an enzyme to attack drug-resistant microbes

Rockefeller University researchers colonized mouse skin with a mix of bacterial cells, some resistant to the antibiotic kanamycin. They made the resistant cells glow (left) and treated the mix with an enzyme that targeted and killed off most resistant cells (right).

Conventional antibiotics are indiscriminate about what they kill, a trait that can lead to complications for patients and can contribute to the growing problems of antibiotic resistance. But a a 'programmable' antibiotic would selectively target only the bad bugs, particularly those harboring antibiotic resistance genes, and leave beneficial microbes alone.

Researchers at Rockefeller University and their collaborators are working on a smarter antibiotic. And in research to be published October 5 in Nature Biotechnology, the team describes a 'programmable' antibiotic technique that selectively targets the bad bugs, particularly those harboring antibiotic resistance genes, while leaving other, more innocent microbes alone.

"In experiments, we succeeded in instructing a bacterial enzyme, known as Cas9, to target a particular DNA sequence and cut it up," says lead researcher Luciano Marraffini, head of the Laboratory of Bacteriology. "This selective approach leaves the healthy microbial community intact, and our experiments suggest that by doing so you can keep resistance in check and so prevent certain types of secondary infections, eliminating two serious hazards associated with treatment by classical antibiotics."

The new approach could, for instance, reduce the risk of C. diff, a severe infection of the colon, caused by the Clostridium difficile bacterium, that is associated with prolonged courses of harsh antibiotics and is a growing public health concern.

The Cas9 enzyme is part of a defense system that bacteria use to protect themselves against viruses. The team coopted this bacterial version of an immune system, known as a CRISPR (clustered regularly interspaced short palindromic repeats) system and turned it against some of the microbes. CRISPR systems contain unique genetic sequences called spacers that correspond to sequences in viruses. CRISPR-associated enzymes, including Cas9, use these spacer sequences as guides to identify and destroy viral invaders.

The researchers were able to direct Cas9 at targets of their choosing by engineering spacer sequences to match bacterial genes then inserting these sequences into a cell along with the Cas9 gene. The cell's own machinery then turns on the system. Depending on the location of the target in a bacterial cell, Cas9 may kill the cell or it may eradicate the target gene. In some cases, a treatment may prevent a cell from acquiring resistance, they found.

"We previously showed that if Cas9 is programmed with a target from a bacterial genome, it will kill the bacteria. Building on that work, we selected guide sequences that enabled us to selectively kill a particular strain of microbe from within a mixed population," says first author David Bikard, a former Rockefeller postdoc who is now at the Pasteur Institute in Paris.

'Programmable' antibiotic harnesses an enzyme to attack drug-resistant microbes 

Omega-3 fatty acids may prevent some forms of depression

Omega-3 fatty acids may prevent some forms of depression 

FDA Approves New Obesity Drug Contrave

In continuation of my update on Contrave

The U.S. Food and Drug Administration's approval of a new weight-loss drug on Wednesday marks the third time the agency has given its blessing to a new diet medication since 2012.

Called Contrave, the medicine is a combination of two approved drugs: naltrexone, which treats alcohol and drug addiction, and bupropion, which treats depression and seasonal affective disorder and is used to help smokers quit.

The agency said in a news release that Contrave can be used by obese adults and by overweight adults who have at least one other weight-related condition or illness, such as high blood pressure or type 2 diabetes.

According to the U.S. Centers for Disease Control and Prevention, more than one-third of adults in the United States are obese, the FDA said in its news release.

"Obesity continues to be a major public health concern," said Dr. Jean-Marc Guettier, director of the division of metabolism and endocrinology products in the FDA's Center for Drug Evaluation and Research. "When used as directed in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, Contrave provides another treatment option for chronic weight management."

FDA Approves New Obesity Drug Contrave  

Anamorelin drug safe and well tolerated in advanced non-small cell lung cancer, Phase III trial reveals

A new drug, anamorelin, improves appetite and body mass in patients with advanced lung cancer who are suffering cancer anorexia and cachexia, according to phase III data presented at the ESMO 2014 Congress in Madrid, Spain.

"Anorexia and cachexia are among the most troubling and distressing symptoms of advanced cancer, for both patients and their families," says the study's principal investigator, Dr Jennifer Temel from the Department of Medicine, Massachusetts General Hospital, Boston, USA.

Symptoms of the wasting syndrome can include a loss of weight and muscles, together with fatigue, weakness, and loss of appetite. The condition is very common in patients with advanced lung cancer. Anamorelin aims to address the symptoms by mimicking the effects of the so-called "hunger hormone" ghrelin, which is secreted by the stomach.

The large, randomized controlled ROMANA 1 and 2 trials are the first phase III studies examining the impact of anamorelin on anorexia-cachexia in patients with advanced lung cancer.

In the ROMANA studies, patients with unresectable stage III or IV non-small cell lung cancer with cachexia were randomized to receive either 100 mg anamorelin or placebo, given orally each day for 12 weeks.

Among 484 participants in ROMANA 1, those taking anamorelin experienced a median increase in lean body mass of 1.10 kg in 12 weeks, compared to a loss of 0.44 kg for those taking placebo. Body weight increased in the anamorelin arm by an average of 2.2 kg, compared to 0.14 kg in the placebo arm of the study. Patient symptoms or concerns regarding anorexia-cachexia, including appetite, also significantly improved over 12 weeks in patients taking anamorelin. The most frequent drug-related adverse events included hyperglycemia and nausea.

In ROMANA 2, 495 participants with advanced non-small cell lung cancer experiened similar benefits. Body weight increased by 0.95 kg on average, compared to a loss of 0.57 kg for those receiving placebo, and patient symptoms/concerns regarding anorexia-cachexia significantly improved over 12 weeks.

Patients receiving anamorelin did not experience improvements in their muscle strength, as measured by hand grip strength, although Temel notes that particular test can be difficult to administer in this patient population.

Anamorelin drug safe and well tolerated in advanced non-small cell lung cancer, Phase III trial reveals