Isis Pharmaceuticals announces initiation of ISIS-SMN Rx Phase 3 study in children with SMA

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced  the initiation of a pivotal Phase 3 study evaluating ISIS-SMNRx in approximately 120 non-ambulatory children with spinal muscular atrophy (SMA). SMA is a severe and rare genetic neuromuscular disease characterized by muscle atrophy and weakness. The Phase 3 study, CHERISH, is the second Phase 3 study Isis has initiated in a global late-stage clinical development program for ISIS-SMNRx. Isis earned a $27 million milestone payment from its development partner, Biogen Idec, for the dosing of the first patient in this study. Isis is also evaluating ISIS-SMNRx in the Phase 3 study, ENDEAR, in infants with SMA. Isis is conducting both Phase 3 studies with agreement from the U.S. Food and Drug Administration (FDA) for special protocol assessments, or SPAs.

Isis Pharmaceuticals announces initiation of ISIS-SMN Rx Phase 3 study in children with SMA

University of Leeds researchers make new synthetic anti-cancer molecule

Researchers at the University of Leeds have made a new synthetic anti-cancer molecule that targets two key mechanisms in the spread of malignant tumours through the body. A study published in the journal PLOS ONE today reports that the synthetic molecule JK-31 blocks the signalling of a "growth factor" chemical that promotes the creation of networks of blood vessels to feed tumours.

But the researchers also found that the new molecule intervened directly in the growth of the cancer itself, inhibiting a protein that controls the division and proliferation of malignant cells.

Dr Vas Ponnambalam, Reader in Human Disease Biology in the University of Leeds' Faculty of Biological Sciences, said: "The ability to mount this two-pronged attack on cancerous growths is exciting. There is a great need for better drugs against cancer than what we currently have and JK31 may represent an important addition to the toolkit for drug makers developing the next generation of drugs."

The researchers observed the effect of the synthetically produced molecule, JK-31, on the growth and proliferation of a model human breast cancer cell line and found that it effectively blocked the protein cyclin-dependent kinase 1 (CDK1), which plays a key part in the process of the division of cancer cells, and therefore inhibited the proliferation of the cells.

In a separate laboratory experiment, they found the same JK-31 molecule also blocked a specific growth factor (VEGF-A) produced by the cancer to attract the growth of blood vessels.

Other molecules exhibiting similar dual effects are known but JK-31 is the only compound so far shown to successfully target CDK1 and block VEGF-A.

University of Leeds researchers make new synthetic anti-cancer molecule

New drug combination shows promise as effective, safe treatment for rheumatoid arthritis

A new drug combination for rheumatoid arthritis treats the disease just as well as other intensive treatment strategies but with less medication and fewer side effects at a significantly lower cost. Doctoral researcher Diederik De Cock (KU Leuven) describes the strategy in a new study published in Annals of Rheumatic Diseases.

Rheumatoid arthritis (RA) is a chronic auto-immune disease that causes pain and stiffness in the joints, fatigue, bone damage and, eventually, loss of mobility. RA afflicts around 1% of people in the western world; in Belgium, 80,000 to 100,000 people currently live with the disease.

Because there is no known cure for RA, physicians focus treatment on suppressing disease activity. Therapies have improved in recent years, and clinical studies show that intensive treatment of early RA can prevent joint damage and improve patients' quality of life.

In the two-year study, called 'CareRA' (Care in early RA), researchers and clinicians in the rheumatology unit at University Hospitals Leuven examined various therapies for early RA. Their goal: to find the optimal combination and dosage of three commonly prescribed antirheumatic drugs (methotrexate, sulfasalazine and leflunomide) in combination with glucocorticoids (a class of steroid hormones).

The researchers divided 290 early RA patients into three treatment groups. Each group received a different combination therapy: 'COBRA Classic' (methotrexate, sulfasalazine and a high first dose of glucocorticoids), 'COBRA Slim' (methotrexate and a moderate dose of glucocorticoids) or 'COBRA Avant-Garde' (methotrexate, leflunomide and a moderate dose of glucocorticoids).

New drug combination shows promise as effective, safe treatment for rheumatoid arthritis

Sulindac drug can protect against oxidative damage due to AMD

In continuation of my update on Sulindac

Scientists at Florida Atlantic University's Charles E. Schmidt College of Science, as well as the Charles E. Schmidt College of Medicine, have found that sulindac, a known anti-inflammatory drug, can protect against oxidative damage due to age-related macular degeneration (AMD), one of the primary causes of vision loss in the elderly. Their findings were released today in an article titled "Pharmacological protection of retinal pigmented epithelial cells by sulindac involves PPAR-α" in the prestigious Proceedings of the National Academy of Sciences.

Sulindac drug can protect against oxidative damage due to AMD

FDA Approves Olysio (simeprevir) in Combination with Sofosbuvir for Genotype 1 Chronic Hepatitis C Infection

In continuation of my update on sofosbuvir

Janssen Therapeutics, Division of Janssen Products, LP (Janssen) announced the U.S. Food and Drug Administration (FDA) has approved Olysio (simeprevir), a hepatitis C virus (HCV) NS3/4A protease inhibitor, in combination withsofosbuvir as an all-oral, interferon- and ribavirin-free treatment option for genotype 1 chronic hepatitis C (CHC) infection in adult patients as part of a combination antiviral treatment regimen. Sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor developed by Gilead Sciences, Inc.

FDA Approves Olysio (simeprevir) in Combination with Sofosbuvir for Genotype 1 Chronic Hepatitis C Infection

New treatment regimen for hepatitis C in transplant patients produces promising results

The investigational three-drug regimen, which produced hepatitis C cure rates of 97 percent, is an oral interferon-free therapy. Previously, the typical treatment for hepatitis C after a liver transplant was an interferon-based therapy, usually given for 48 weeks. It had a much lower response rate, had a risk of organ rejection and was poorly tolerated because of the immunosuppressants required to prevent rejection. The new oral regimen -- ABT-450, ombitasvir and dasabuvir (with or without ribavirin) -- produces significantly fewer side effects and is prescribed for 24 weeks.

New treatment regimen for hepatitis C in transplant patients produces promising results

Study reports anti-cancer activity in mice treated with experimental drug TAK-733

Study reports anti-cancer activity in mice treated with experimental drug TAK-733

TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc.

Ref: http://www.heemd.com/news/?md=1510006/
http://www.medchemexpress.com/TAK-733.html

Eribulin drug has minor added benefit in one patient group, indication of lesser benefit in others

In continuation of my update on Eribulin

Eribulin (trade name: Halaven) is approved for women with locally advanced or metastatic breast cancer in whom the disease has progressed despite prior drug therapy. The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in a dossier assessment whether the drug offers an added benefit over the appropriate comparator therapy in these patient groups.

According to the findings, there are both positive and negative effects. There is proof of minor added benefit for one group of patients. For other groups, there are hints or indications of lesser benefit.

Second assessment of eribulin

IQWiG already presented a dossier assessment of eribulin in February 2012. The subsequent decision on the added benefit made by the Federal Joint Committee (G-BA) was limited until April 2014. In addition, the drug manufacturer meanwhile obtained approval for an expanded therapeutic indication: In March 2011 eribulin was only available for patients who have progressed further after at least two chemotherapeutic regimens. Since June 2014, however, the drug can already be used after one unsuccessful treatment attempt. Hence there were two reasons ─ independent from each other ─ for the reassessment of eribulin.

G-BA specified appropriate comparator therapies

When the G-BA specified the appropriate comparator therapy, it distinguished between several treatment situations: The first one refers to patients who are not eligible for further chemotherapy with a taxane or an anthracycline. In this situation, eribulin was to be compared with individual chemotherapy containing the drugs capecitabine or vinorelbine.

In patients for whom taxanes or anthracyclines are principally still an option, eribulin was to be compared with an individual chemotherapy containing a taxane or an anthracycline.

Eribulin drug has minor added benefit in one patient group, indication of lesser benefit in others

FDA Approves Dual-Chamber Syringe for Abilify Maintena (aripiprazole) for Schizophrenia

In continuation of my update on aripiprazole

We know that, Aripiprazole (brand names: Abilify, Aripiprex) is a atypical antipsychotic. It is primarily used in the treatment of schizophrenia, bipolar disorder, major depressive disorder (as an add on to other treatment),tic disorders, and irritability associated with autism. 

It was approved by the U.S. Food and Drug Administration (FDA) for schizophrenia on November 15, 2002 and the European Medicines Agency on 4 June 2004; for acute manic and mixed episodes associated with bipolar disorder on October 1, 2004; as an adjunct for major depressive disorder on November 20, 2007; and to treat irritability in children with autism on 20 November 2009.  Likewise it was approved for use as a treatment for schizophrenia by the TGA of Australia in May 2003.  It is a partial dopamine agonist

Aripiprazole was developed by Otsuka in Japan, and in the United States, Otsuka America markets it jointly with Bristol-Myers Squibb.

FDA Approves Dual-Chamber Syringe for Abilify Maintena (aripiprazole) for Schizophrenia

FDA Approves Ofev (nintedanib) for Idiopathic Pulmonary Fibrosis

In continuation of update on nintedanib

The U.S. Food and Drug Administration today approved Ofev (nintedanib) for the treatment of idiopathic pulmonary fibrosis (IPF).

Idiopathic pulmonary fibrosis is a condition in which the lungs become progressively scarred over time. As a result, patients with IPF experience shortness of breath, cough, and have difficulty participating in everyday physical activities. Current treatments for IPF include oxygen therapy, pulmonary rehabilitation, and lung transplant.

FDA Approves Ofev (nintedanib) for Idiopathic Pulmonary Fibrosis

FDA Approves Revised Indication for Ozurdex for the Treatment of Diabetic Macular Edema

In continuation of my update on dexamethasone

Allergan, Inc., announced today that the U.S. Food and Drug Administration (FDA) has approved Ozurdex (dexamethasone intravitreal implant) 0.7 mg, a sustained-release biodegradable steroid implant, for the treatment of diabetic macular edema (DME). Ozurdex was originally approved in June as a treatment for DME in adult patients who have an artificial lens implant (pseudophakic) or who are scheduled for cataract surgery (phakic). Based on ongoing review of clinical data demonstrating efficacy and safety, the FDA has now approved Ozurdex for use in the general DME patient population.

FDA Approves Revised Indication for Ozurdex for the Treatment of Diabetic Macular Edema

FDA Approves Esbriet (pirfenidone) for Idiopathic Pulmonary Fibrosis

Pirfenidone is a drug developed by several companies worldwide, including InterMune Inc. (now part of Roche), Shionogi Ltd., and GNI Group Ltd., for the treatment of idiopathic pulmonary fibrosis (IPF). In 2008, it was first approved in Japan for the treatment of IPF after clinical trials, under the trade name of Pirespa by Shionogi & Co. In October 2010, the Indian Company Cipla launched it as Pirfenex. In 2011, it was approved for use in Europe for IPF under the trade name Esbriet.  was approved in Canada in 2012 under the trade name Esbriet; and was approved in the United States in October 2014 under the same name. In September 2011, the Chinese State Food and Drug Administration provided GNI Group Ltd with new drug approval of pirfenidone in China,^[3] and later manufacture approval in 2013 under the trade name of Etuary. 

In continuation of my update on pirfenidone

FDA Approves Esbriet (pirfenidone) for Idiopathic Pulmonary Fibrosis

FDA Approves Ofev (nintedanib) for Idiopathic Pulmonary Fibrosis

In continuation of update on nintedanib

The U.S. Food and Drug Administration today approved Ofev (nintedanib) for the treatment of idiopathic pulmonary fibrosis (IPF).

Idiopathic pulmonary fibrosis is a condition in which the lungs become progressively scarred over time. As a result, patients with IPF experience shortness of breath, cough, and have difficulty participating in everyday physical activities. Current treatments for IPF include oxygen therapy, pulmonary rehabilitation, and lung transplant.

FDA Approves Ofev (nintedanib) for Idiopathic Pulmonary Fibrosis

An apple a day could keep obesity away

Sientists at Washington State University have concluded that non digestible compounds in apples -- specifically, Granny Smith apples  may help prevent disorders associated with obesity. The study, thought to be the first to assess these compounds in apple cultivars grown in the Pacific Northwest, appears in October's print edition of the journal Food Chemistry.

"We know that, in general, apples are a good source of these nondigestible compounds but there are differences in varieties," said food scientist Giuliana Noratto, the study's lead researcher. "Results from this study will help consumers to discriminate between apple varieties that can aid in the fight against obesity."

The tart green Granny Smith apples benefit the growth of friendly bacteria in the colon due to their high content of non-digestible compounds, including dietary fiber and polyphenols, and low content of available carbohydrates. Despite being subjected to chewing, stomach acid and digestive enzymes, these compounds remain intact when they reach the colon. Once there, they are fermented by bacteria in the colon, which benefits the growth of friendly bacteria in the gut.

The study showed that Granny Smith apples surpass Braeburn, Fuji, Gala, Golden Delicious, McIntosh and Red Delicious in the amount of nondigestible compounds they contain.

"The nondigestible compounds in the Granny Smith apples actually changed the proportions of fecal bacteria from obese mice to be similar to that of lean mice," Noratto said.

An apple a day could keep obesity away 

Researchers identify compounds that could lead to discovery of new drugs for African sleeping sickness

In early drug discovery, you need a starting point, says North­eastern Uni­ver­sity asso­ciate pro­fessor of chem­istry and chemical biology Michael Pollastri.

In a new research paper published Thursday in the journal PLOS Neglected Tropical Diseases, Pollastri and his colleagues present hun­dreds of such starting points for poten­tially treating African sleeping sick­ness, a deadly disease that claims thousands of lives annually.

Pol­lastri, who runs Northeastern's Lab­o­ra­tory for Neglected Dis­ease Drug Dis­covery, and co- collaborators at the Spanish National Research Council for Scientific Research worked with global health­care com­pany GlaxoSmithKline to screen and test more than 42,000 chem­ical com­pounds against the par­a­sites that cause African sleeping sickness. In their paper, they report iden­ti­fying nearly 800 com­pounds that rep­re­sent good options for early drug discovery.

"Having this many good starting points for discovery of new drugs for sleeping sick­ness is a big deal and could ultimately lead to a cure," Pol­lastri said.

Pol­lastri also high­lighted another exciting component to this project. Previously, he created a data- sharing portal where sci­en­tists and researchers can access and con­tribute to each other's work on neglected tropical diseases. This new research on African sleeping sickness will be the first data to be deposited on the portal, which was sup­ported by a crowd­funding campaign.

"This is a venue where other people, particularly medical chemists from around the world, can con­tribute to the project in one way or the other," Pollastri said.

Researchers identify compounds that could lead to discovery of new drugs for African sleeping sickness

MIT researchers develop new way to model effects of cancer-causing genetic mutations

Sequencing the genomes of tumor cells has revealed thousands of genetic mutations linked with cancer. However, sifting through this deluge of information to figure out which of these mutations actually drive cancer growth has proven to be a tedious, time-consuming process.

MIT researchers have now developed a new way to model the effects of these genetic mutations in mice. Their approach, based on the genome-editing technique known as CRISPR, is much faster than existing strategies, which require genetically engineering mice that carry the cancerous mutations.

"It's a very rapid and very adaptable approach to make models," says Thales Papagiannakopoulos, a postdoc at MIT's Koch Institute for Integrative Cancer Research and one of the lead authors of the paper, which appears in the Oct. 22 online edition ofNature. "With a lot of these mutations, we have no idea what their role is in tumor progression. If we can actually understand the biology, we can then go in and try targeted therapeutic approaches."

Led by Papagiannakopoulos, graduate student Francisco Sanchez-Rivera, the paper's other lead author, and Koch Institute director Tyler Jacks, the paper's senior author, the team used CRISPR to accurately reproduce the effects of two well-known lung cancer genes. They also modeled a gene called APC, whose role in lung cancer was not previously known.

This approach could be used to study nearly any gene in many different types of cancer, the researchers say. "There has to be a functional way of assessing the role of these cancer-gene candidates as they appear in sequencing studies," Sanchez-Rivera says. "The system we developed fills that gap immediately because you can do it very rapidly and very precisely."

Ref  http://newsoffice.mit.edu/2014/fast-modeling-cancer-mutations-1022

MIT researchers develop new way to model effects of cancer-causing genetic mutations

Scientists develop new drug as alternative to antibiotics

In a breakthrough, scientists have developed the first effective alternative to antibiotics that may aid the fight against drug-resistant infections. 

In a small patient trial, the drug was shown to be effective at eradicating the superbug Methicillin-resistant Staphylococcus aureus (MRSA). 

Researchers said it is unlikely that the infection could develop resistance against the new treatment, which is already available as a cream for skin infections. 

They hope to develop a pill or an injectable version of the drug within five years. 

The treatment marks "a new era in the fight against antibiotic-resistant bacteria," according to Mark Offerhaus, chief executive of the biotechnology company Micreos, which is behind the advance. 

The treatment attacks infections in an entirely different way from conventional drugs and, unlike them, exclusively targets the Staphylococcus bacteria responsible for MRSA, and leaves other microbes unaffected. 

The approach is inspired by naturally occurring viruses that attack bacteria using enzymes called endolysins. It uses a 'designer' endolysin, Staphefekt, which the scientists engineered to latch on to the surface of bacteria cells and tear them apart, 'The Times' reported. 

"Endolysins exist in nature, but we've made a modified version that combines the bit that is best at binding to the bacteria with another bit that is best at killing it," said Bjorn Herpers, a clinical microbiologist, who tested the drug at the Public Health Laboratory in Kennemerland, the Netherlands. 

Conventional antibiotics need to reach the inside of the cell to work, and part of the reason they are becoming less effective is that certain strains of bacteria, such as MRSA, have evolved impenetrable membranes. 

Scientists develop new drug as alternative to antibiotics  

Analgesics, anti-inflammatory drugs have beneficial effect on treatment of depression

Analgesics and anti-inflammatory drugs used against muscle pain and arthritis may have a beneficial effect on depression symptoms....

Ordinary over the counter painkillers and anti-inflammatory drugs purchased from pharmacies may also be effective in the treatment of people suffering of depression.

This is shown by the largest ever meta-analysis that has just been published by a research group from Aarhus University in the American scientific journal JAMA Psychiatry. The meta-analysis is based on 14 international studies with a total 6,262 patients who either suffered from depression or had individual symptoms of depression.

Up to 15 per cent of the Danish population can expect to suffer from depression at some point in their lives. The World Health Organisation (WHO) estimates that depression is one of the top five reasons for loss of quality of life and also life years. Thus, it is a very serious condition, one where researchers all over the world are constantly trying to find more effective treatments.

In recent years research has demonstrated a correlation between depression and physical illnesses, such as painful conditions or infections in the individual patient.

"The meta-analysis supports this correlation and also demonstrates that anti-inflammatory medication in combination with antidepressants can have an effect on the treatment of depression. When combined they give an important result which, in the long term, strengthens the possibility of being able to provide the individual patient with more personalized treatment options," says MD-student Ole Köhler, who is first author of the scientific article and a member of the research group from Aarhus University.

Analgesics, anti-inflammatory drugs have beneficial effect on treatment of depression

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