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).

Dual-acting hybrid drug could be a promising new weapon against drug-resistant malaria

A combination of artemisinin and another drug (artemisinin combination therapy, ACT) is currently the best malaria treatment recommended by the World Health Organization. In early 2015, artemisinin-resistant malaria was confirmed in five countries in Southeast Asia: Cambodia, Laos, Myanmar, Thailand, and Vietnam. Even more worrying, malaria cases that are resistant to practically all drugs have begun to emerge along the Thailand-Cambodia border. Such cases do not respond to ACT; thus, new therapies that are effective for resistant malaria are urgently needed.

For a therapy to be effective, it needs to counteract the resistance of malaria to existing drugs. Malaria drugs, such as chloroquine and artemisinin, work within the digestive vacuole of the malaria parasite, which serves as the stomach of the parasite. The killing action of chloroquine is better understood than that for artemisinin. Once chloroquine enters the parasite's "stomach," the stomach membrane traps the drug inside (similar to a window closing and locking) and the high levels of drug can then effectively kill the parasite. However, in a resistant malaria parasite, the stomach membrane is mutated so that it cannot keep the drug inside the stomach, just like a window with a broken lock. Since the drug is no longer concentrated inside the stomach, it can no longer kill the malaria parasite effectively.

Associate Professor Kevin Tan of the Department of Microbiology &amp; Immunology and Associate Professor Brian Dymock of the Drug Development Unit and the Department of Pharmacy have now developed a hybrid drug that combines parts of chloroquine and a chemoreversal agent. This gives the hybrid drug a "dual acting" mechanism: a killing factor (chloroquine-derived) and a second component that acts on that faulty window of the parasite's stomach so it can now close again (the chemoreversal agent). The drug becomes concentrated inside the stomach of the drug-resistant parasite and can kill the parasite.

Dual-acting hybrid drug could be a promising new weapon against drug-resistant malaria: A combination of artemisinin and another drug (artemisinin combination therapy, ACT) is currently the best malaria treatment recommended by the World Health Organization.

Novel antibiotics to overcome antibacterial resistance

Small and innovative pharmaceutical companies, with products in early stages of development, presented some of their novel approaches and antimicrobial therapies under development during a dedicated session at the annual congress (ECCMID) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in Amsterdam.

Dr. Ursula Theuretzbacher, the founder of the Centre for Anti-Infective Agents in Vienna, led the session, which gave an overview of the research and development programmes that are driving innovation in this critical space.

At a time of transition with big pharma continuing to move away from the development of antibacterial treatments, these small biotechnology companies and start-ups are rising to the challenge and filling the gap through the discovery and development of novel therapies.

Dr. Ursula Theuretzbacher remarked: “we are pleased to see a number of highly promising antibacterial drugs of a new class and or a new mode of action now in the research or close to the preclinical phase. To aid the development of more drug candidates, crucial to increasing the chances of a sufficient number reaching the clinical stage, innovative researchers in small companies or universities are pursuing a range of non-traditional approaches in addition to classical ones.

New approaches highlighted at pipeline corner fall into three key categories: targeted therapies, adjunctive therapies and potentiators.

• Targeted therapies - traditional antibiotics and antibodies that are active against a single pathogen, especially Staphylococcus aureus or Pseudomonas aeruginosa
• Adjunctive therapies – including drugs that target virulence factors, biofilm formation, immune system stimulation, modifying the microbiome, and phages. All such approaches require an active antibiotic
• Potentiators – an adjuvant drug, such as beta-lactamase-inhibitors or efflux pump inhibitors, improve the activity of an antibiotic by inhibiting resistance determinants, either facilitating the penetration or changing the sensitivity of the bacterial cell

Spero, Cidara and Melinta Therapeutics attend from the USA and Vitas Pharma from India. European biotechnology companies making presentations included Discuva, Bioversys and Morphochem. In addition, a publicly funded research institution, the German Centre for Infection Research, was also a key feature at the 2016 pipeline corner.    

Novel antibiotics to overcome antibacterial resistance: Small and innovative pharmaceutical companies, with products in early stages of development, presented some of their novel approaches and antimicrobial therapies under development during a dedicated session at the annual congress (ECCMID) of the European Society of Clinical Microbiology and Infectious Diseases(ESCMID) in Amsterdam.

Substances from tequila plant may help treat osteoporosis

Mexican scientist identified substances from the plant that enhance absorption of calcium in the body.

Apart from being the raw material for making a very traditional drink in Mexico, the blue variety of the Agave tequilana has substances capable of improving the absorption of calcium and magnesium, essential minerals to maintain bone health. This has been demonstrated by research conducted at the Center for Research and Advanced Studies (Cinvestav) in center Mexico.

Dr. Mercedes López, leader of the project, states that "the consumption of fructans contained in the agave, in collaboration with adequate intestinal micriobiota, promotes the formation of new bone, even with the presence of osteoporosis."

To reach this conclusion, the research team conducted various experiments with animal models. The procedure consisted of removing the ovaries from female mice in order to induce osteoporosis. The next step was to administer agave fructans and eight weeks later a femur sample was taken to measure the absorption of minerals and osteocalcin, protein that indicates the production of new bone.

"It was found that mice that consumed this fructans synthesized nearly 50 percent more of such protein, in addition that the diameter of their bones was higher compared with the subjects which were not supplied with derivatives of the agave" she reports.

This substances reach the large intestine intact and interact with the microbiota living there to become short-chain fatty acids. These catch minerals available in the tract and help to transport them through the cells.

"This way, we have a second chance to take advantage of the nutrients that were no longer available to the body. However, it is very important that people have a healthy intestinal microbiome, because only then it is possible that bacteria ferment fructans to transform them into fatty acids, "says Dr. Lopez.

The results provide the possibility of developing an alternative in the treatment of osteoporosis, a disease that, according to the latest statistics from the International Osteoporosis Foundation, affects 200 million of people worldwide, which means that one of every five fractures, in the population with more than 50 years of age, is related to the disease.

Substances from tequila plant may help treat osteoporosis: Mexican scientist identified substances from the plant that enhance absorption of calcium in the body.

Breast cancer medication letrozole could increase ovulation in women with PCOS

In continuation of my update on Letrozole

A medicine used in breast cancer treatment is now considered the best option for treating the most common cause of infertility.

Letrozole has been found to increase ovulation in women with Polycystic Ovarian Syndrome (PCOS), a common form of ovulation dysfunction, leading to a 40 percent increase in pregnancy rates and more ovulation and live births than Clomid, the previous standard.

In breast cancer patients, Letrozole decreases the amount of estrogen, but a side effect is increased ovulation.

"We have found out that the hormonal messages affect different areas of the body in different ways," said Dr. Stephanie Estes, a board certified fertility specialist and director of the Robotic Surgery Program at Penn State Health Milton S. Hershey Medical Center.

She suggests that patients whose infertility is caused by irregular ovulation ask their providers about letrozole, since news of its effectiveness as an infertility treatment hasn't spread very quickly. "It is easy to take, has a low rate of multiple births, and fewer side effects than Clomid," Estes said.

If infertility is caused by male factors or simply unexplainable, doctors may recommend other medicines, injectables, inseminations or in-vitro fertilization (IVF), depending on the diagnosis.

"You always have to look at the underlying cause to pick which treatment is correct," Estes said.

Intra-uterine insemination (IUI) places concentrated sperm directly into the woman's uterus so it doesn't have so far to travel and thus increases chances of fertilization. With IVF, the woman's eggs are harvested and combined with sperm in an embryology laboratory and then an embryo is placed into the uterus.

"IVF is becoming more and more successful, so its availability to patients has improved," Estes said. "More states and companies are seeing the importance of family-building within the job, so now there is a lot more coverage for these treatments."

Estes said most insurance companies will cover fertility testing, even if they don't cover the treatments. "Many people just wait and hope, and their family tells them it will happen when it is supposed to happen," Estes said. "But why not come and see what the issue might be?"

Breast cancer medication letrozole could increase ovulation in women with PCOS: A medicine used in breast cancer treatment is now considered the best option for treating the most common cause of infertility.