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.

New extended-release pills could reduce dosage frequency of some drugs

Researchers from MIT and Brigham and Women's Hospital have designed a new type of pill that, once swallowed, can attach to the lining of the gastrointestinal tract and slowly release its contents. The tablet is engineered so that one side adheres to tissue, while the other repels food and liquids that would otherwise pull it away from the attachment site.

Such extended-release pills could be used to reduce the dosage frequency of some drugs, the researchers say. For example, antibiotics that normally have to be taken two or three times a day could be given just once, making it easier for patients to stick to their dosing schedule.

"This could be adapted to many drugs. Any drug that is dosed frequently could be amenable to this kind of system," says Giovanni Traverso, a research affiliate at MIT's Koch Institute for Integrative Cancer Research, a gastroenterologist at Brigham and Women's Hospital, and one of the senior authors of a paper describing the device in the April 6 issue of the journal Advanced Healthcare Materials.

Robert Langer, the David H. Koch Institute Professor and a member of the Koch Institute, is also a senior author of the paper. The paper's lead author is Young-Ah Lucy Lee, a technical assistant at the Koch Institute.

Two faces

Over the past several decades, Langer's lab has developed many types of materials that can be implanted in the body or attached to the skin for long-term drug release. To achieve similar, long-term drug release in the gastrointestinal tract, the researchers focused on a type of material known as mucoadhesives, which can stick to the mucosal linings of organs such as the stomach.

Scientists have previously explored using this kind of material for drug delivery to the GI tract, but it has proven difficult because food and liquid in the stomach become stuck to the tablet, pulling it away from the tissue before it can deliver its entire drug payload.

"The challenge with mucoadhesives is that the GI tract is a very rough and abrasive environment," says Lee, a 2014 Wellesley College graduate who began this project as her senior thesis.

To overcome this challenge, the researchers decided to create a dual-sided device, also called a Janus device after the two-faced Roman god. One side sticks to mucosal surfaces, while the other is omniphobic, meaning that it repels everything it encounters.

New extended-release pills could reduce dosage frequency of some drugs: Researchers from MIT and Brigham and Women's Hospital have designed a new type of pill that, once swallowed, can attach to the lining of the gastrointestinal tract and slowly release its contents. The tablet is engineered so that one side adheres to tissue, while the other repels food and liquids that would otherwise pull it away from the attachment site.