Thursday, July 28, 2016

Zonisamide relieves myoclonus dystonia motor symptoms

A randomised crossover trial shows that zonisamide significantly improves motor symptoms and related disability in adults with myoclonus dystonia.

Zonisamide structure.svg

Myoclonus dystonia is very rare, and Marie Vidailhet (Hôpital Pitié-Salpêtrière, Paris, France) and co-researchers stress that their study "is the first controlled therapeutic trial to be conducted in this setting."

It involved 23 patients with myoclonus dystonia who were randomly assigned to receive the benzisoxazole derivative zonisamide (up to 300 mg/day) or placebo for a 6-week dose-escalation period followed by 3 weeks at the highest tolerated dose. After a 5-week washout period, the patients were switched to the other treatment.

From a baseline of 28 points on the Unified Myoclonus Rating Scale (UMRS) section 4, the severity of action myoclonus improved by a median of 5 points during the zonisamide treatment period relative to the placebo period. And from a baseline of 7 points on the UMRS section 5, myoclonus-related functional disability improved by a significant 2 points with zonisamide relative to placebo. Both of these differences were statistically significant.

Patients also had significantly improved dystonia, by 3 points on the Burke-Fahn-Marsden Dystonia Rating Scale, during zonisamide versus placebo treatment, although related disability was unaffected.
"Zonisamide may thus be considered as a therapeutic option for patients with mild to moderate [myoclonus dystonia] and for patients with severe forms who refuse or are not eligible for deep brain stimulation", write the researchers in Neurology.

They note that the benefits observed with zonisamide in their study are less than those reported for deep-brain stimulation.

Adverse events were reported by 83% of patients during the zonisamide treatment period and by 74% during the placebo period. Asthenia was more common during the zonisamide versus placebo phases (65 vs 17%), as were mood swings (35 vs 26%).

The researchers note that patients only received 9 weeks of treatment in their study, leaving the longer-term benefits and safety profile to be determined.

And they add that, because myoclonus dystonia "usually starts before age 10, the use of zonisamide in children will need to be addressed, although studies in epilepsy show that zonisamide is well-tolerated in this age group."

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Zonisamide relieves myoclonus dystonia motor symptoms: A randomised crossover trial shows that zonisamide significantly improves motor symptoms and related disability in adults with myoclonus dystonia.

Wednesday, July 27, 2016

Common antihistamine may partially reverse damage to visual system in multiple sclerosis patients

A common antihistamine used to treat symptoms of allergies and the common cold, called clemastine fumarate, partially reversed damage to the visual system in people with multiple sclerosis (MS) in a preliminary study released today that will be presented at the American Academy of Neurology's 68th Annual Meeting in Vancouver, Canada, April 15 to 21, 2016.

Clemastine.svg

The study involved people with MS and optic neuropathy, which is damage to the nerve that sends information from the eye to the brain. In people with MS, the immune system destroys myelin, the protective coating around the nerves, which then leads to damage along the nerves, slowing signals to and from the brain. Optic nerve damage is a common consequence of the disease.

"This study is exciting because it is the first to demonstrate possible repair of that protective coating in people with chronic demyelination from MS," said study author Ari Green, MD, of the Multiple Sclerosis Center at UC San Francisco, and a member of the American Academy of Neurology. "This was done using a drug that was identified at UCSF only two-and-a-half years ago as an agent with the potential to help with brain repair."

The five-month study involved 50 people with an average age of 40 who had MS for an average of five years and had mild disability. They all had evidence of a stable chronic optic neuropathy, meaning that they were not recovering from a recent optic neuritis.

Participants performed vision tests at the start and end of the study. For one test, called a visual evoked potential, the time for transmission of signal from the retina to the visual cortex was recorded. To be included in the study, participants had to have a delay in transmission time beyond 118 milliseconds in at least one eye and had to have evidence that they had an adequate number of nerve fibers to reinsulate. An improvement in the delay in transmission is considered a biomarker of myelin repair.

For the first three months of the study, people were given either the antihistamine clemastine fumarate or a placebo. For the second two months, those initially given the drug received the placebo and vice versa.

During the study, delays were reduced by an average of slightly less than two milliseconds in each eye per patient among those who received the antihistamine.

"While the improvement in vision appears modest, this study is promising because it is the first time a drug has been shown to possibly reverse the damage done by MS," said Green. "Findings are preliminary, but this study provides a framework for future MS repair studies and will hopefully herald discoveries that will enhance the brain's innate capacity for repair."


Common antihistamine may partially reverse damage to visual system in multiple sclerosis patients: A common antihistamine used to treat symptoms of allergies and the common cold, called clemastine fumarate, partially reversed damage to the visual system in people with multiple sclerosis (MS) in a preliminary study released today that will be presented at the American Academy of Neurology's 68th Annual Meeting in Vancouver, Canada, April 15 to 21, 2016.

Tuesday, July 26, 2016

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: 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.

Monday, July 25, 2016

Willow herb extracts may be beneficial in treating multi-drug resistant bacterial and fungal infections

 

A common herb, Epilobi Hirsuti (see pic) could help reduce antibiotic doses and result in less severe side effects in treatments against multi-drug resistant microorganisms.

Although often considered a weed, due to its anti-inflammatory and antioxidant properties, willow herb has long enjoyed a solid reputation for easing problems of the prostate gland and urinary tract. New tests confirm that combining some of the commonly used antibiotics with great willow herb extracts may be beneficial in treating bacterial and fungal infections as well.

Many strains of bacteria are becoming resistant to even the strongest antibiotics, causing deadly infections and becoming a global health issue. In America alone this accounts for at least 23,000 deaths each year, as an abuse of antibiotics promotes the development of antibiotic-resistant bacteria. As more and more bacterial strains do not react to any of currently known antibiotics, scientists often turn to nature, screening for plant-derived compounds to identify new drug leads which would be able to control the populations of multi-drug resistant bacteria. An article published now online in Open Chemistry suggests that some of the willow herb extracts exert a synergistic effect with common antibiotics.

Using different solvents, the scientists from the National Institute of Chemical-Pharmaceutical R&amp;D, ICCF-Bucharest in Romania prepared a series of great willow herb extracts. They then screened the extracts - rich in phenolic acids and flavonoids -  for their antimicrobial effect against selected bacterial and fungal strains, to further test different concentrations of extracts along with a series of antibiotics for the possible effects of these combinations on the observed antimicrobial effect.

Interestingly enough, they were able to observe the synergistic effect on bacterial strains which were resistant to some of the commonly used antibiotics. The authors hence suggest that this development could lead to reducing the antibiotic doses, and consequently  to less severe side effects in therapies against multi-drug resistant microorganisms. Courtesy of the herbal healer, some bacterial or fungal infections can be treated with better effects when compared to a therapy based only on antibiotics, as it has potential to influence the antimicrobial effect of some common antibiotics and antibiotics may be co-administered with plant-derived compounds to potentiate their antimicrobial effect.

Ref : http://www.degruyter.com/view/j/chem.2016.14.issue-1/chem-2016-0004/chem-2016-0004.xml


Willow herb extracts may be beneficial in treating multi-drug resistant bacterial and fungal infections: A common herb could help reduce antibiotic doses and result in less severe side effects in treatments against multi-drug resistant microorganisms.

Friday, July 22, 2016

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.

Thursday, July 21, 2016

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.

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.svg 
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 etexilate structure.svgDabigatran        Rivaroxaban2DCSD.svg Rivaroxaban (BAY 59-7939)


Apixaban.svgApixaban Edoxaban.svgEdoxaban



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.

Wednesday, July 20, 2016

Cholesterol-fighting drug molecule can kill prostate cancer cells

Ro 48-8071 fumarate ≥98% (HPLC), solid  

(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.

Tuesday, July 19, 2016

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.

Scutellaria baicalensis flowers.jpg

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.

Monday, July 18, 2016

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.

Friday, July 15, 2016

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.svg
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.