Intestinal bacteria can be used to reduce cancer risk, reveals UCLA study

Researchers have shown that various types of intestinal bacteria might be factors in both causing and preventing obesity, and in other conditions and diseases. Now, a UCLA study suggests that it could also potentially be used to reduce the risk for some types of cancer.

The research, published online April 13 in the peer-reviewed journal PLOS ONE, offers evidence that anti-inflammatory "health beneficial" gut bacteria can slow or stop the development of some types of cancer.

Ultimately, doctors might be able to reduce a person's risk for cancer by analyzing the levels and types of intestinal bacteria in the body, and then prescribing probiotics to replace or bolster the amount of bacteria with anti-inflammatory properties, said Robert Schiestl, professor of pathology, environmental health sciences and radiation oncology at UCLA and the study's senior author.

"It is not invasive and rather easy to do," he said.

Over millions of years, gut bacteria have evolved into both good and bad types: The good ones have anti-inflammatory properties and the bad ones promote inflammation. The human body typically contains about 10 trillion bacterial cells, compared with only 1 trillion human cells.

Schiestl and his colleagues isolated a bacterium called Lactobacillus johnsonii 456, which is the most abundant of the beneficial bacteria, and which has some pretty useful applications outside of medicine. "Since it is a Lactobacillus strain, it makes excellent yogurt, kefir, kombucha and sauerkraut."

In the UCLA study the bacterium reduced gene damage and significantly reduced inflammation — a critical goal because inflammation plays a key role in many diseases, including cancer, neurodegenerative diseases, heart disease, arthritis and lupus, and in the aging process.

Previous research led by Schiestl presented the first evidence of a relationship between intestinal microbiota and the onset of lymphoma, a cancer that originates in the immune system. The new study explains how this microbiota might delay the onset of cancer, and suggests that probiotic supplements could help keep cancer from forming.

For both studies, Schiestl and his team used mice that had mutations in a gene called ATM, which made them susceptible to a neurologic disorder called ataxia telangiectasia. The disorder, which affects 1 in 100,000 people, is associated with a high incidence of leukemia, lymphomas and other cancers.

The mice were divided into two groups — one that was given only anti-inflammatory bacteria and the other that received a mix of inflammatory and anti-inflammatory microbes that typically co-exist in the intestines.

In the Cancer Research paper, Schiestl and his team showed that in the mice with more of the beneficial bacteria, the lymphoma took significantly longer to form.

In the new study, the researchers analyzed the metabolites — molecules produced by the gut's natural metabolic action — in the mice's urine and feces. The scientists were surprised to find that the mice that were receiving only the beneficial microbiota produced metabolites that are known to prevent cancer. Those mice also had more efficient fat and oxidative metabolism, which the researchers believe might also lower the risk for cancer.

Intestinal bacteria can be used to reduce cancer risk, reveals UCLA study: Researchers have shown that various types of intestinal bacteria might be factors in both causing and preventing obesity, and in other conditions and diseases. Now, a UCLA study suggests that it could also potentially be used to reduce the risk for some types of cancer.

New oral blood thinners can decrease stroke risk in atrial fibrillation patients without frequent monitoring

In continuation of my update on dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa).

A new generation of blood thinners can reduce the risk of stroke in patients with atrial fibrillation, without requiring frequent monitoring and dietary restrictions.

But special attention must be given to the patient's age, kidney function and other factors before prescribing the new medications, according to a review article by neurologists at Loyola Medicine and Loyola University Chicago Stritch School of Medicine.

The report by Rochelle Sweis, DO and José Biller, MD, is published in the journal Current Treatment Options in Cardiovascular Medicine.

Atrial fibrillation (AFib) is the most common type of irregular heartbeat, and the prevalence is increasing as the population ages. In AFib, electrical signals that regulate the heartbeat become erratic. Instead of beating regularly, the upper chambers of the heart quiver and blood doesn't flow well. Blood clots can form, migrate to the brain and cause strokes. AFib is associated with a fivefold increase in the risk of stroke.

Blood thinning medications decrease the stroke risk by approximately 70 percent. For 60 years physicians have prescribed warfarin (Coumadin) and other blood thinners known as vitamin K antagonists. These medications have been proven to be effective in reducing the risk of blood clots and strokes. But they require continual monitoring and dose adjustments to ensure the drugs thin the blood enough to prevent clots, but not enough to increase the risk of major bleeding. Patients also must restrict their consumption of foods rich in vitamin K, such as spinach, Brussels sprouts, kale, parsley and green tea.

 

Warfarin

The new blood thinners include dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa). In the right patient population, the new drugs are a safe and effective option for treating atrial fibrillation, Drs. Sweis and Biller write.

Dabigatran         Rivaroxaban (BAY 59-7939)

Apixaban Edoxaban

New oral blood thinners can decrease stroke risk in atrial fibrillation patients without frequent monitoring: A new generation of blood thinners can reduce the risk of stroke in patients with atrial fibrillation, without requiring frequent monitoring and dietary restrictions.

Cholesterol-fighting drug molecule can kill prostate cancer cells

  

(Ro 48-8071 fumarate)

[4′-[6-(Allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate 

Standard treatment for prostate cancer can include chemotherapy that targets receptors on cancer cells. However, drug-resistant cancer cells can emerge during chemotherapy, limiting its effectiveness as a cancer-fighting agent. Researchers at the University of Missouri have proven that a compound initially developed as a cholesterol-fighting molecule not only halts the progression of prostate cancer, but also can kill cancerous cells.

"Cholesterol is a molecule found in animal cells that serves as a structural component of cell membranes. When tumor cells grow, they synthesize more cholesterol," said Salman Hyder, the Zalk Endowed Professor in Tumor Angiogenesis and professor of biomedical sciences in the MU College of Veterinary Medicine and the Dalton Cardiovascular Research Center. "Often, cancer patients are treated with toxic chemotherapies; however, in our study, we focused on reducing the production of cholesterol in cancer cells, which could kill cancer cells and reduce the need for toxic chemotherapy."

Currently, treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptors located in the cancer cells, which normally bind with hormones such as testosterone. Anti-hormone therapies, or chemical castration, also may be used in the fight against prostate cancer.

"Although tumor cells may initially respond to these therapies, most eventually develop resistance that causes prostate cancer cells to grow and spread," Hyder said. "Cholesterol also can contribute to the development of anti-hormone resistance because cholesterol is converted into hormones in tumor cells; therefore, these cholesterol-forming pathways are attractive therapeutic targets for the treatment of prostate cancer."

Using a compound developed by Roche Pharmaceuticals for the treatment of high cholesterol called RO 48-8071, Hyder and his team administered the molecule to human prostate cancer cells. They found that the compound was effective in reducing human prostate cancer cell growth. Subsequent studies also found that the compound caused cancer cell death.

Armed with this information, Hyder and the team then tested the results in mice with human prostate cancer cells. Following injection of the compound, Hyder found that the molecule was effective in reducing tumor growth.

These findings suggest that the potential cholesterol drug, when used in combination with commonly used chemotherapeutic drugs, could represent a new therapeutic approach in the fight against prostate cancer, Hyder said.

Cholesterol-fighting drug molecule can kill prostate cancer cells: Standard treatment for prostate cancer can include chemotherapy that targets receptors on cancer cells. However, drug-resistant cancer cells can emerge during chemotherapy, limiting its effectiveness as a cancer-fighting agent. Researchers at the University of Missouri have proven that a compound initially developed as a cholesterol-fighting molecule not only halts the progression of prostate cancer, but also can kill cancerous cells.

Traditional Chinese medicinal plant produces compounds that may help to kill human cancers

New research led by Professor Cathie Martin of the John Innes Centre has revealed how a plant used in traditional Chinese medicine produces compounds which may help to treat cancer and liver diseases.

The Chinese skullcap, Scutellaria baicalensis - otherwise known in Chinese medicine as Huang-Qin - is traditionally used as a treatment for fever, liver and lung complaints.

Previous research on cells cultured in the lab has shown that certain compounds called flavones, found in the roots of this plant, not only have beneficial anti-viral and anti-oxidant effects, but they can also kill human cancers while leaving healthy cells untouched. In live animal models, these flavones have also halted tumour growth, offering hope that they may one day lead to effective cancer treatments, or even cures.

As a group of compounds, the flavones are relatively well understood. But the beneficial flavones found in Huang-Qin roots, such as wogonin and baicalin, are different: a missing - OH (hydroxyl) group in their chemical structure left scientists scratching their heads as to how they were made in the plant.

Professor Cathie Martin, lead author of the paper published in Science Advances, explains: "Many flavones are synthesised using a compound called naringenin as a building block. But naringenin has this -OH group attached to it, and there is no known enzyme that will remove it to produce the flavones we find in Huang-Qin roots."

Working in collaboration with Chinese scientists, Cathie and her team explored the possibility that Huang-Qin's root-specific flavones (RSFs) were made via a different biochemical pathway. Step-by-step, the scientists unravelled the mechanism involving new enzymes that make RSFs using a different building block called chrysin.

"We believe that this biosynthetic pathway has evolved relatively recently in Scutellariaroots, diverging from the classical pathway that produces flavones in leaves and flowers, specifically to produce chrysin and its derived flavones," said Professor Martin.

"Understanding the pathway should help us to produce these special flavones in large quantities, which will enable further research into their potential medicinal uses. It is wonderful to have collaborated with Chinese scientists on these traditional medicinal plants. Interest in traditional remedies has increased dramatically in China since Tu Youyou was awarded the Nobel Prize for Medicine in 2015 for her work on artemisinin. It's exciting to consider that the plants which have been used as traditional Chinese remedies for thousands of years may lead to effective modern medicines."

Traditional Chinese medicinal plant produces compounds that may help to kill human cancers: New research led by Professor Cathie Martin of the John Innes Centre has revealed how a plant used in traditional Chinese medicine produces compounds which may help to treat cancer and liver diseases.

Palovarotene drug may prevent multiple musculoskeletal problems linked with FOP

We know that, Palovarotene (R-667, RO-3300074) is a highly selective retinoic acid receptor gamma (RAR-γ) agonist that is under investigation as a potential treatment for fibrodysplasia ossificans progressiva (FOP), an ultra-rare and severely disabling genetic disease characterized by extra-skeletal bone formation (heterotopic ossification or HO) in muscle and soft tissues. 

Palovarotene2DACS.svg

Palovarotene is being developed by Clementia Pharmaceuticals and was granted Fast Track and orphan drug designations by the United States Food and Drug Administration for the treatment of FOP and Orphan Medicinal Product Designation by the European Medicines Agency (EMA) in 2014. Phase II clinical studies are currently underway

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New research in laboratory animals suggests that the drug palovarotene may prevent multiple skeletal problems caused by a rare but extremely disabling genetic bone disease, and may even be a candidate for use in newborn babies with the condition. Scientists at The Children's Hospital of Philadelphia, who previously repurposed the drug to prevent excess bone formation in animal models of fibrodysplasia ossificans progressiva (FOP), have extended that research in animals carrying the exact human disease-causing mutation.

In humans with FOP, an activating mutation in the ACVR1 gene triggers extraskeletal cartilage and bone formation and accumulation starting in early childhood. The extraskeletal bone occurs in muscles and other tissues where it does not belong. This pathological process, collectively called heterotopic ossification (HO), causes progressive loss of skeletal motion and hampers breathing and swallowing.

Currently untreatable and painful, FOP often causes death early in adulthood.

"This work represents a big step toward therapy," said co-study leader, Maurizio Pacifici, Ph.D., a developmental biologist and director of Orthopedic Research in the Division of Orthopedic Surgery at The Children's Hospital of Philadelphia (CHOP). "The mice used in this study were engineered to carry the human mutation that causes FOP, and the drug showed powerful and comprehensive benefits for skeletal growth and function in addition to inhibiting HO. If these results translate to humans, we may be able to treat children with FOP early in life, before the disease progresses."

The research appeared online March 12 in the Journal of Bone and Mineral Research.

Palovarotene drug may prevent multiple musculoskeletal problems linked with FOP: New research in laboratory animals suggests that the drug palovarotene may prevent multiple skeletal problems caused by a rare but extremely disabling genetic bone disease, and may even be a candidate for use in newborn babies with the condition.

AstraZeneca reports new Phase I extended follow-up data on osimertinib in NSCLC patients at ELCC 2016

AstraZeneca today reported new Phase I extended follow-up data on osimertinib in both first- and second-line treatment of patients with non-small cell lung cancer (NSCLC), at the European Lung Cancer Conference (ELCC) 2016. Late-breaker presentations reinforced the efficacy and safety profile for osimertinib previously seen in the AURA clinical trials programme.

osimertinib

Phase I data from the AURA trial on osimertinib investigated as first-line treatment in 60 patients (pooled 80mg and 160mg dose cohorts) with epidermal growth factor receptor (EGFR) mutation-positive advanced NSCLC showed an objective response rate (ORR, a measurement of tumour shrinkage) of 77% (95% confidence interval (CI): 64%-87%) and a progression-free survival (PFS) of 19.3 months, with 55% of patients remaining progression-free at 18 months (95% CI: 41%-67%).1 Median duration of response (DoR) was non-calculable (NC) (95% CI: 12.5 months to NC) at the time of data cut off, with 53% of patients continuing to respond at 18 months (95% CI: 36%-67%).1 Of the 60 first-line patients, five had tumours also harbouring the T790M mutation at diagnosis (known as de novo patients) and all five of these patients showed durable responses. The most common adverse events were rash (78% overall; 2% ≥Grade 3), diarrhoea (73% overall; 3% ≥Grade 3), dry skin (58% overall; 0 ≥Grade 3) and paronychia (50% overall; 3% ≥Grade 3). All of the Grade 3 or above events in these categories occurred at the 160mg dose.

Klaus Edvardsen, Vice President, Clinical Oncology and Interim Head of Oncology, Global Medicines Development at AstraZeneca said:

In a Phase I study with osimertinib as first-line therapy in EGFR-mutation positive NSCLC, we are seeing consistently durable responses. In many cases, responses continue for at least 18 months including in a small group of patients with the T790M mutation detectable at diagnosis. The ongoing Phase III FLAURA trial will further characterise the potential of osimertinib 80mg in the first-line EGFRm setting.

AstraZeneca reports new Phase I extended follow-up data on osimertinib in NSCLC patients at ELCC 2016: AstraZeneca today reported new Phase I extended follow-up data on osimertinib in both first- and second-line treatment of patients with non-small cell lung cancer (NSCLC), at the European Lung Cancer Conference (ELCC) 2016. Late-breaker presentations reinforced the efficacy and safety profile for osimertinib previously seen in the AURA clinical trials programme.

Proliposomal ropivacaine may offer valuable new option for pain relief

A new "proliposomal" preparation of the local anesthetic drug ropivacaine may provide a valuable new option for pain relief in some clinical situations, with key advantages over other types of slow-release local anesthetics, suggest a pair of reports in Anesthesia & Analgesia.

Ropivacaine

Proliposomal ropivacaine can deliver long-lasting pain relief with a single injection, with easier preparation and storage than current slow-release local anesthetic products, according to initial studies in animals and human volunteers. The new formulation was developed and tested by Dr. Yehuda Ginosaur of Hadassah Hebrew University Medical Center, Jerusalem, and colleagues.

New Product Doesn't Become 'Liposomal' Until It's Injected

Liposomal preparations are used as a way of delivering controlled-release of drugs or other products (for example, cosmetics). Liposomes are nano-sized "bubbles" that release their contents as they dissolve. Liposomal local anesthetics are currently available, but have some important limitations. They are complicated and expensive to manufacture and have a short shelf-life—less than one or two months, even with refrigeration.

To address these shortcomings, Dr. Ginosaur and colleagues developed the new "proliposomal" ropivacaine oil. Comparatively easy to prepare, proliposomal ropivacaine oil can be stored at room temperature for up to two years. Liposomes appear, and begin releasing their ropivacaine contents, only when the oil comes into contact with aqueous (water-containing) solutions—including blood plasma.

The researchers initially tested proliposomal ropivacaine in pigs, showing that it gradually released ropivacaine into the animals' circulation. Ropivacaine levels persisted, along with effective control of pain behaviors, for up to four days after application to a surgical wound.

Dr. Ginosaur and colleagues then proceeded to studies in human volunteers, who were injected with proliposomal or plain ropivacaine at separate locations in the lower back. While the amount injected was the same, the ropivacaine concentration of the proliposomal formulations was eight times higher: four percent versus 0.5 percent.

Proliposomal ropivacaine may offer valuable new option for pain relief: A new 'proliposomal' preparation of the local anesthetic drug ropivacaine may provide a valuable new option for pain relief in some clinical situations, with key advantages over other types of slow-release local anesthetics, suggest a pair of reports in Anesthesia & Analgesia.

VIEKIRAX and EXVIERA achieve high SVR rates in GT1 and GT4 hepatitis C virus infected patients

ombitasvir

paritaprevir

ritonavir 

dasabuvir 

ribavirin (RBV).

AbbVie, a global biopharmaceutical company,    announced new real-world data showing 96 percent of genotype 1 (GT1) patients (n=486/505 assessable for analysis) and 100 percent (n=53/53) of genotype 4 (GT4) patients achieved sustained virologic response at 12 weeks post-treatment (SVR12). These data support results seen in Phase 3 clinical trials for chronic GT1 or GT4 hepatitis C virus (HCV) infected patients treated with VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) and EXVIERA® (dasabuvir tablets) with or without ribavirin (RBV).

The analysis also reports safety outcomes from 1,017 people with GT1 or GT4 chronic HCV enrolled in the German Hepatitis C-Registry (DHC-R) who have initiated treatment, representing a diverse group of patients seen in real-world settings being treated with VIEKIRAX and EXVIERA. The results will be presented orally today at The International Liver Congress™ (ILC) 2016 in Barcelona, Spain.

“Real-world studies complement randomized controlled trials and help to further enhance our knowledge of VIEKIRAX and EXVIERA in everyday clinical practice,” said Heiner Wedemeyer, M.D., research group leader, department of gastroenterology, hepatology and endocrinology at Hannover Medical School in Germany. “The effectiveness and safety results shown across a broad cross-section of patients in this particular study provide helpful insight into treatment of real-world patients.”

The safety study population (n=1,017) was reflective of a diversity of patients seen in routine clinical practice, including patients with cirrhosis (22 percent) and those previously treated for HCV (59 percent). More than half of patients (59 percent) were taking medicines for other medical conditions.

“These results provide additional insights that complement the Phase 3 clinical trial data for VIEKIRAX and EXVIERA,” said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie. “We believe further ongoing real-world studies across multiple countries will enrich our understanding of HCV treatment.”

Among the patients included in the safety analysis (n=1,017), the rate of discontinuation due to adverse events (AEs) was low (1.5 percent).1 The most common AEs (≥ 5 percent) were fatigue (24 percent), pruritus (10 percent), headache (9 percent), insomnia (6 percent) and nausea (5 percent). Serious AEs were reported in 1 percent (n=5/480) of patients receiving VIEKIRAX and EXVIERA without RBV and in 3 percent (n=16/537) of patients receiving VIEKIRAX and EXVIERA with RBV. Fifteen patients discontinued treatment due to AEs, while two patients died due to myocardial infarction or stroke, respectively. Both cases were assessed as not related to study treatment.

VIEKIRAX and EXVIERA achieve high SVR rates in GT1 and GT4 hepatitis C virus infected patients: AbbVie, a global biopharmaceutical company, today announced new real-world data showing 96 percent of genotype 1 (GT1) patients (n=486/505 assessable for analysis) and 100 percent (n=53/53) of genotype 4 (GT4) patients achieved sustained virologic response at 12 weeks post-treatment (SVR12).

Combination of sugar and polyphenols may prevent occurrence of neurodegenerative disease

Catherine Aaron and Gabrielle Beaudry were 17 when they knocked on the door of the laboratory of Alex Parker, a neuroscience researcher at the University of Montreal Hospital Research Centre (CRCHUM). While students at Collège Jean-de-Brébeuf in Montreal, they were looking for a mentor for an after-school research project. Two and half years later, the results of this scientific adventure were published today in theJournal of Agricultural and Food Chemistry.

"We wanted to test the effect of a natural product on a neurodegenerative disease such as Alzheimer's. Professor Parker had already discovered that sugar prevents the occurrence of amyotrophic lateral sclerosis (ALS) in an animal model of the disease, the C. elegans worm. That's how we got the idea of maple syrup, a natural sugar produced in Quebec," said Beaudry.

Supervised by PhD student Martine Therrien and Alex Parker, Aaron and Beaudry added maple syrup to the diet of these barely 1 mm-long nematodes. "We just gave them a supplement of maple syrup at various concentrations and compared with a control group that had a normal diet," said Aaron. "After twelve days, we counted under the microscope the worms that were moving and those that were paralyzed. The worms that had consumed the highest dose of syrup were much less likely to be paralyzed."

Alex Parker's C. elegans worms are genetically modified to express a protein involved in ALS in motor neurons - TDP-43. "When they are adults, around 12 days, their motor neurons break down. Normally, at two weeks of life, 50% of the worms are completely paralyzed. But among those that received a diet enriched with 4% maple syrup, only 17% were paralyzed. We can therefore conclude that maple syrup protects neurons and prevents the development of amyotrophic lateral sclerosis in C. elegans worms," said Parker, a researcher at the CRCHUM and professor at the Faculty of Medicine, University of Montreal.

How can we explain this dramatic effect? "Sugar is good for the nervous system. Diseased neurons require more energy to combat toxic proteins. But maple syrup is rich in polyphenols, powerful antioxidants found in certain foods. We isolated phenols contained in the maple syrup, and we showed that two polyphenols in particular, gallic acid and catechol, have a neuroprotective effect. In pure maple syrup, these polyphenols are found in low concentrations. Probably a combination of sugar and polyphenols prevents the occurrence of the disease in worms," said Therrien, a PhD student at the CRCHUM.

Combination of sugar and polyphenols may prevent occurrence of neurodegenerative disease: Catherine Aaron and Gabrielle Beaudry were 17 when they knocked on the door of the laboratory of Alex Parker, a neuroscience researcher at the University of Montreal Hospital Research Centre. While students at Collège Jean-de-Brébeuf in Montreal, they were looking for a mentor for an after-school research project. Two and half years later, the results of this scientific adventure were published today in the Journal of Agricultural and Food Chemistry.

AbbVie's ABT-493 and ABT-530 achieve high SVR rates in GT1 chronic HCV patients who failed previous therapy with DAAs

ABT-493

ABT-530

ribavirin (RBV

AbbVie, a global biopharmaceutical company, today announced that 91 percent (n=20/22) of genotype 1 (GT1) chronic hepatitis C virus (HCV) infected patients who failed previous therapy with direct-acting antivirals (DAAs) achieved SVR12 with 12 weeks of ABT-493 and ABT-530 with ribavirin (RBV) in the primary intent-to-treat analysis. Additionally, 86 percent (n=19/22) of GT1 patients who received ABT-493 and ABT-530 without RBV, achieved SVR12.[i] SVR12 was achieved in 95 percent of patients with and without RBV (n=20/21, n=19/20; respectively) in a modified intent-to-treat analysis, excluding patients who did not achieve SVR for reasons other than virologic failure.

The results were evaluated in the ongoing MAGELLAN-1 study of AbbVie’s once-daily, investigational, pan-genotypic regimen of co-formulated ABT-493 (300mg) and ABT-530 (120mg) for the retreatment of non-cirrhotic patients with GT1 chronic HCV who have failed previous therapy with DAAs. These data will be presented today at The International Liver Congress™ (ILC) 2016 in Barcelona, Spain.

“Retreatment options for those patients who have previously failed therapy are limited, and present a particular challenge for treating physicians,” said Fred Poordad, M.D., vice president of academic and clinical affairs at The Texas Liver Institute in San Antonio. “The high SVR rates seen in the ongoing MAGELLAN-1 study are significant as they show promise in addressing this particular clinical challenge.”

No patients discontinued treatment due to adverse events, and two patients experienced virologic failure, one from each arm. The most common adverse events (≥10 percent of patients overall; n=44) were headache (30 percent), fatigue (27 percent) and nausea (20 percent).

“While high virologic cure rates have been demonstrated in clinical studies with current DAA regimens, we recognize that not all patients achieve a cure,” said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie. “Through our ongoing clinical development program, we are striving to give HCV patients a potential option for retreatment.”

AbbVie's ABT-493 and ABT-530 achieve high SVR rates in GT1 chronic HCV patients who failed previous therapy with DAAs: AbbVie, a global biopharmaceutical company, today announced that 91 percent (n=20/22) of genotype 1 (GT1) chronic hepatitis C virus (HCV) infected patients who failed previous therapy with direct-acting antivirals (DAAs) achieved SVR12 with 12 weeks of ABT-493 and ABT-530 with ribavirin (RBV) in the primary intent-to-treat analysis.

Daily dose of coffee could help reverse non-alcoholic fatty liver disease

Adding coffee to the diet of people with non-alcoholic fatty liver disease (NAFLD) could help reverse the condition, according to a new study conducted in mice presented at The International Liver Congress 2016 in Barcelona, Spain.

The study found that a daily dose of coffee (equivalent to six cups of espresso coffee for a 70kg person) improved several key markers of NAFLD in mice that were fed a high fat diet. These mice also gained less weight than others fed the same diet without the dose of caffeine.

The scientists also showed how coffee protects against NAFLD by raising levels of a protein called Zonulin (ZO)-1, which lessens the permeability of the gut. Experts believe that increased gut permeability contributes to liver injury and worsens NAFLD. People suffering from NAFLD can develop scaring of the liver, also known as fibrosis, which can progress to a potentially life-threatening condition known as cirrhosis.

"Previous studies have confirmed how coffee can reverse the damage of NAFLD but this is the first to demonstrate that it can influence the permeability of the intestine," said Vincenzo Lembo, at the University of Napoli, Italy and study author. "The results also show that coffee can reverse NAFLD-related problems such as ballooning degeneration, a form of liver cell degeneration."

Researchers analysed three different groups of mice over a 12 week period. Group one received a standard diet, group two had a high fat diet and group three was given a high fat diet plus a decaffeinated coffee solution.

Coffee supplementation to a high fat diet significantly reversed levels of cholesterol (p<0.001), alanine aminotransferase (an enzyme which levels increase in the blood when the liver is damaged) (p<0.05), amount of fat in the liver cells (steatosis) (p<0.001) and ballooning degeneration (p<0.05). The combination of coffee and a high fat diet also reduced weight gain over time (p=0.028) in the mice. The study results suggest that coffee supplementation could cause variations in the intestinal tight junctions, which regulate the permeability of the intestine.

Daily dose of coffee could help reverse non-alcoholic fatty liver disease

TDF, entecavir duo 'highly effective' for difficult-to-treat chronic HBV

The combination of tenofovir disoproxil fumarate (TDF) and entecavir induces a high rate of viral suppression in patients with chronic hepatitis B virus (HBV) infection who have failed multiple nucleos(t)ide analogue (NA) regimens, phase IIIb results indicate.

  

Entecavir                                                                         Tenofovir disoproxil fumarate 

The dual therapy could be "a highly effective option for difficult-to-treat multidrug-resistant" chronic HBV patients, the team writes in Liver International.

The 64 patients enrolled in this study had persistent viraemia, defined as serum HBV DNA levels above 60 IU/mL despite a minimum 24 weeks of rescue therapy, and documented genotypic resistance to one or more nucleoside analogue and a nucleotide analogue.

Treatment with TDF 300 mg and entecavir 1 mg once a day led to complete virological response (CVR), defined as HBV DNA levels under 60 IU/mL, in over half (56.3%) of the study population at 12 weeks. The CVR rate rose to 67.2% at week 24 and 85.9% at week 48.

The proportion of patients who achieved HBV DNA levels below 12 IU/mL, the lower limit of detection in this study, was 32.8%, 51.6% and 62.5% at weeks 12, 24 and 48, respectively.

The antiviral efficacy of the dual regimen was not affected by baseline viral load or the presence of baseline resistance mutations, report Sang Hoon Ahn (Yonsei University College of Medicine, Seoul, Republic of Korea) and fellow ESTEEM investigators.

However, a smaller proportion of participants with baseline triple resistance to lamivudine, adefovir and entecavir achieved CVR at week 48 relative to those with single or double resistance at baseline, at 67.7% versus rates ranging from 83.3% to 100.0%.

Virological breakthroughs occurred in five patients, but were transient in all cases and HBV DNA levels declined as treatment continued, say the researchers. And they add that none of the eight participants without CVR at week 48 had resistance mutations to TDF or any novel mutations.

TDF, entecavir duo 'highly effective' for difficult-to-treat chronic HBV: The combination of tenofovir disoproxil fumarate and entecavir induces a high rate of viral suppression in patients with chronic hepatitis B virus infection who have failed multiple nucleos(t)ide analogue regimens, phase IIIb results indicate.

New plant-derived oral drug can prevent progression of multiple sclerosis

   

An international research team has demonstrated that a new plant-derived drug can block the progression of multiple sclerosis (MS).

University of Queensland researcher Dr Christian Gruber said the breakthrough could be a step forward in preventing and treating MS and other autoimmune diseases.

"This is a really exciting discovery because it may offer a whole new quality of life for people with this debilitating disease," he said.

The new drug is expected to be taken by mouth, in contrast to some current MS treatments where patients need to have frequent injections.

MS is a chronic incurable condition marked by attacks that bring gradual deterioration in the patient's health. About 23,000 people are affected in Australia and 2.5 million worldwide.

Dr Gruber said the new drug -- named T20K -- was extracted from a traditional medicinal plant, the Oldenlandia affinis.

The drug treatment had been successful in an animal model, and patent applications filed in several countries.

"Phase one clinical trials could begin as early as 2018," Dr Gruber said.

"Licences have been assigned to Cyxone, a company established last year to develop this new class of drugs for the treatment of autoimmune diseases.

"Cyxone's immediate focus is on bringing T20K through the pre-clinical program required for delivering a safe, orally active drug."

Dr Gruber said the new treatment arose from a synthesised plant peptide, a class of drugs known as cyclotides.

"Cyclotides are present in a range of common plants, and they show significant potential for the treatment of auto immune diseases," he said.

"The T20K peptides exhibit extraordinary stability and chemical features that are ideally what you want in an oral drug candidate."

New plant-derived oral drug can prevent progression of multiple sclerosis: An international research team has demonstrated that a new plant-derived drug can block the progression of multiple sclerosis (MS).