Sanofi-Aventis’ Teriflunomide Comes Up Trumps in Two-Year Phase III MS Trial ....

Sanofi-aventis reported positive two-year data from a Phase III trial with its oral disease-modifying multiple sclerosis (MS) drug teriflunomide. Results from the international thousand-patient TEMSO study showed that both evaluated doses of teriflunomide reduced the annualized MS relapse rate by 31% in comparison with placebo. The 14 mg and 7 mg teriflunomide doses resulted in a reduction in the risk of disability progression by 30% and 24%, respectively, when compared with placebo.  

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Onyx Pharmaceuticals announces delay in NDA filing for carfilzomib

In continuation of my update on carfilzomib

Onyx Pharmaceuticals announces delay in NDA filing for carfilzomib

Onyx Pharmaceuticals announces delay in NDA filing for carfilzomib

In continuation of my update on carfilzomib

Onyx Pharmaceuticals announces delay in NDA filing for carfilzomib

FDA approves fingolimod drug for multiple sclerosis...

Fingolimod (see structure), a drug modified from a fungus  (Isaria sinclairii), a structural analogue of sphingosine and gets phosphorylated by sphingosine kinases in the cell originally found in Asian wasps, prevents autoimmune attacks by trapping white blood cells in the body's lymph nodes. Two large Phase III clinical studies published in February found that fingolimod was at least twice as effective in preventing MS attacks when compared to placebo or current treatments. 

Research on additional uses for fingolimod continues at the University of Chicago, including a new clinical trial in patients with progressive MS, for which there are no available treatments. With fingolimod adding to the recent boom of new MS therapies, and with a number of clinical trials for new therapies in progress, patients should be sure to seek out an experienced MS center for their care.

As per the claim by the lead researcher, Anthony Reder, MD, Professor of Neurology at the University of Chicago Medical Center,  fingolimod is first oral medication for multiple sclerosis was approved  by the Food & Drug Administration. He also claims that'

"We have six drugs right now, and they all involve injections. So the convenience alone of a pill is a major change in how we treat MS."

Hope people suffering from MS, (A chronic, neurologic disorder, which affects roughly 400,000 Americans and 2.5 million people around the world.  MS can cause issues with walking and movement, fatigue, weakness, pain, and loss of vision. Patients with relapsing-remitting MS suffer from intermittent and unpredictable immune system attacks that can damage the brain, spinal cord, and eyes) breathe a sigh of relief..

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Rufinamide therapy is effective in reducing partial seizure frequency...

Rufinamide(see structure) is an anticonvulsant medication and a triazole derivative, was developed in 2004 by Novartis Pharma, AG, and is manufactured by Eisai. It is used in combination with other medication and  therapy to  treat  Lennox–Gastaut  syndrome and various other seizure disorders. Rufinamide.

Rufinamide was approved by the US FDA on November 14, 2008 as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 4 years and older and adults. Its official FDA-approved labeling does not mention use in the treatment of partial seizures inasmuch as clinical trials submitted to the FDA were marginal.

Interestingly, now researchers from the Arkansas Epilepsy Program found treatment with rufinamide results in a significant reduction in seizure frequency compared with placebo, for patients with uncontrolled partial-onset seizures (POS).

Researchers found that treatment with rufinamide resulted in a statistically significant reduction in total partial seizure frequency compared with placebo. Results also showed a 50% reduction in responder rate and total partial seizure frequency rate in patients treated with rufinamide. Several exploratory efficacy variables, including at least 75% responder rate and increase in the number of seizure-free days, were also associated with notably better results for rufinamide.

With respect to efficacy by seizure type, rufinamide was significantly superior to placebo for complex partial seizures, the most common seizure type, and numerically superior to placebo for simple partial seizures and secondarily generalized partial seizures. The median reduction in secondarily generalized partial seizures of 40% in this study is consistent with that previously observed at identical rufinamide dosage. As per the claim by the lead researcher Dr. Victor Biton,

"Overall, there were no significant pharmacokinetic (PK) effects on either rufinamide or any second-generation AED when given with other medications."

The research team confirmed PK results found in previous studies-showing lower oral bioavailability of rufinamide at higher doses, increased clearance of rufinamide with increasing body weight, and no effect of prolonged rufinamide dosing on the PK of rufinamide.

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Ingredient (Triclosan) in soap points toward new drugs for Toxoplasmosis !

We know that, Triclosan (see structure)  is an antibacterial ingredient in some soaps, toothpastes, odor-fighting socks, and even computer keyboards. Now researchers lead by Dr. Rima McLeod from The University of Chicago, have come up with interesting findings about this drug, i.e., triclosan's molecular structure can be used as  the model for developing other potential medications for toxoplasmosis. 

In the study, Rima McLeod and colleagues point out that toxoplasmosis is one of the world's most common parasitic infections (spread by the parasite Toxoplasma gondii,  T. gondii), from contact with feces from infected cats, eating raw or undercooked meat, and in other ways. Many have no symptoms because their immune systems keep the infection under control and the parasite remains inactive. But it can cause eye damage and other problems, even becoming life threatening in individuals with immune systems weakened by certain medications and diseases like HIV infection, which allow the parasite to become active again, and in some persons without immune compromise. Most current treatments have some potentially harmful side effects and none of them attack the parasite in its inactive stage.

The scientists knew from past research that triclosan has a powerful effect in blocking the action of a key enzyme that T. gondii uses to live. As per the claim by the researchers, Triclosan, however, cannot be used as a medication because it does not dissolve in the blood, how ever  one can use triclosan's molecular structure as the model for developing other potential medications, including some that show promise as more effective treatments for the disease.  Hope this research will lead to a better drug than Triclosan without any carcinogenecity and many other side effects associated with this drug..

Ref : http://pubs.acs.org/stoken/presspac/presspac/abs/10.1021/jm9017724

Phase 3 clinical study demonstrates efficacy of metformin therapy in type 2 diabetes

Phase 3 clinical study demonstrates efficacy of metformin therapy in type 2 diabetes

Enzyme telomerase activating compound discovered....

In continuation of telomerase and its importance...

Sierra Sciences, in collaboration with TA Sciences, Geron Corporation, PhysioAge, and the Spanish National Cancer Research Center (CNIO), has announced the first compound ever discovered that activates the enzyme telomerase in the human body - a critical prerequisite for technology that could arrest or reverse the aging process in humans. This compound is a natural product derived nutraceutical known as TA-65.

TA-65, exclusively licensed to TA Sciences from Geron Corporation, is a >95% pure single chemical entity isolated from a proprietary extract of the dried root of Astragalus membranaceus and formulated into 5- to 10-mg capsules with inert excipients. Starting doses of 5–10 mg/day were considered safe on the basis of historical usage of extracts. Some subjects increased their dosage after several months on the product to 25–50 mg/day. Cumulative dose consumed during the year was recorded for each subject and used for preliminary dose–response analysis.

Researchers discovered that TA-65 was associated with a statistically significant "age-reversal" effect in the immune system, in that it led to declines in the percentage of senescent cytotoxic T cells and natural killer cells after six to twelve months of use. In addition, further analysis with automated high-throughput confocal microscopy (HT-qFISH) revealed a decline in the percentage of white blood cells with critically short telomeres after twelve to eighteen months of use.

Telomere shortening is thought to be the "clock of aging" contained within the human body. It has been repeatedly demonstrated that a human cell that does not undergo telomere shortening will divide indefinitely and is, by all available measurements, immortal.

Researchers reports that TA-65 can cause telomerase, an enzyme that lengthens telomeres, to become active in human cells.  Telomerase activation by TA-65 was shown to lengthen the shortest telomeres in humans, potentially extending human lifespan and healthspan. Telomerase activation is thought to be a keystone of future regenerative medicine and a necessary condition for clinical immortality. Although TA-65 is probably too weak to completely arrest the aging process, it is the first telomerase activator recognized as safe for human use.

"We are on the cusp of curing aging," said William Andrews, Ph.D., co-author of this study and President and CEO of Sierra Sciences, LLC. "TA-65 is going to go down in history as the first supplement you can take that doesn't merely extend your life a few years by improving your health, but actually affects the underlying mechanisms of aging. Better telomerase inducers will be developed in the coming years, but TA-65 is the first of a whole new family of telomerase-activating therapies that could eventually keep us young and healthy forever."

Telomerase activation has potential medical applications beyond extending human lifespan.  Epidemiological studies have shown that short telomeres in humans are a risk factor for diseases including, among others, atherosclerosis, diabetes, Alzheimer's, and cancer. The present study also reports encouraging news on the effect of TA-65 on the body's immune system. Infectious diseases lead to telomere shortening in the immune system, as immune cells divide to fight infections. Telomerase activation should prevent this telomere shortening and allow the body's immune system to fight a chronic infection indefinitely.

The present study on TA-65 lends support to this hypothesis. In individuals infected with CMV, a virus which prematurely ages the immune system and significantly reduces life expectancy, TA-65 caused an apparent "age reversal" of approximately 5 to 20 years based on one biomarker of immune aging. For the same reason, telomerase activation is a potential treatment for AIDS.

"We tend to see HIV turning into AIDS when the cells of the immune system develop critically short telomeres," said Andrews...

HIV can essentially cause the immune system to die of old age while the majority of the body is still young and therefore the researchers are hopeful that a telomerase activator could theoretically prevent an HIV-positive individual from ever developing AIDS....

Ref : http://www.liebertonline.com/doi/abs/10.1089/rej.2010.1085

Method developed to reduce acrylamide (carcinogen) formation during production of potatoes and coffee...

A small research-based Norwegian company has developed a method to reduce the formation of the carcinogenic compound acrylamide during industrial production of potatoes and coffee. International food giants are paying attention. In 2002 Swedish researchers found that the carcinogenic compound acrylamide was present in many foods - a discovery that grabbed international headlines and frightened consumers and food safety authorities around the world. What these production foods had in common was high-temperature cooking which formed a crust or browning reaction. The acrylamide issue has had dramatic consequences for the manufacturers involved.

Since then a great deal of research has been focused on acrylamide. The compound has been found in bread, some types of crackers and sweet biscuits, deep-fried potato products and coffee. Research has also been carried out on the compound's effects on humans and on production methods that can reduce or remove acrylamide from our foods.

Norwegian Hans Blom  and his research team found a method that limits the formation of acrylamide during the production of potato products and coffee. It was the patent for this method that provided the springboard for the company Zeracryl.

"Our method is based on lactic acid fermentation," explains Dr Blom. "Acrylamide is formed as a reaction between the amino acid asparagine and simple sugars such as glucose and fructose. Put simply, the lactic acid bacteria remove these compounds and inhibit the formation of acrylamide."

The team's ongoing experiments show that 10 to 15 minutes' immersion in lactic acid bacteria culture before cooking reduces acrylamide formation in the final product by roughly 90 per cent.

Zeracryl will continue its work in the research project Lactic acid fermentation as a tool to reduce formation of acrylamide in fried potato products and roasted coffee in cooperation with the international food conglomerate Nestlé, the Norwegian producers of potato products Hoff AS and Maarud, and the research institute Nofima. The project is supported by the Research Council of Norway's Food Programme and is scheduled to run until 2012...

Ref 1. http://www.angelfire.com/az/sthurston/acrylamides_cancer_causing.html
      2. Zeracryl 

Synthetic derivative of Retinoic acid can induce cell death

Retinoic acid (RA), a natural derivative of vitamin A, is the basis of a number of treatments against cancer. Nevertheless, it has certain disadvantages, such as the possibility of the appearance of retinoic acid syndrome, present in 25 % of cases and which can lead to death. The development of 4-HPR (see structure -Fenretinide 4-hydroxy(phenyl)retinamide) a synthetic derivative of RA, has meant a considerable advance due to its greater efficacy compared to its predecessor. It is able to induce the death of tumour cells as the method for reducing their proliferation, in a precise manner and without serious damage to surrounding tissue. Moreover, it halts the referred-to retinoic acid syndrome and even functions with cells that resist RA. In vitro studies corroborate its effectiveness as a chemopreventive agent and also as a chemotherapeutic agent, both with leukaemias and with ovary, breast or brain tumour cells.

Biologist Ms Aintzane Apraiz studied the 4-HPR in depth, focusing on the causes that, according to previous research, give rise to this ability to induce cell death. To this end, she applied this synthetic derivative to acute lymphoblastic leukaemia T cells (LLA-T). Her PhD thesis, defended at the University of the Basque Country (UPV/EHU), is entitled Role of sphingolipids and oxidative stress in the antineoplasic activity of 4-HPR: study in a leucemia model.

Amongst the various processes that can induce cell death, in the case of 4-HPR, apoptosis is outstanding; a precise mechanism and without inflammatory processes or serious damage to surrounding tissue. According to Ms Apraiz, previous research on LLA-T undertaken by the team of which she is a member, showed that 4-HPR induced a massive accumulation of ceramides (lipids of the cell membrane) and of reactive oxygen species (ROS), both of which can cause cell death. 

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Methylphenidate facilitates recovery from drug addiction...

A brain-scanning study at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory, conducted with collaborators from Stony Brook University, reveals that an oral dose of methylphenidate, commonly known as Ritalin, improves impaired brain function and enhances cognitive performance in people who are addicted to cocaine.

Researchers were encouraged by the fact that, methylphenidate does decrease behaviors such as risk taking and impulsivity and improves brain function and cognitive performance in a range of other conditions that also affect the brain's prefrontal cortex, including attention deficit hyperactivity disorder (ADHD), some forms of dementia, and certain kinds of brain injury. To begin with Goldstein's (lead researcher)  group performed functional magnetic resonance imaging (fMRI) on 13 cocaine users and 14 healthy control subjects who were asked to perform a cognitive task after being given either a low oral dose of methylphenidate (20 milligrams) or a placebo. The task involved pushing a button to correctly identify the color of a printed word; some words had to do with drug use, others were "neutral." Subjects received monetary rewards for correct answers. The scientists were particularly interested in two parts of the prefrontal cortex previously shown to be impaired during this cognitive activity in cocaine-addicted individuals.

"These regions help to regulate emotion, cognition, and behavior in response to salient stimuli - the things we find particularly interesting or relevant," Goldstein said. "Because drug users have deficits in these regions, they may have less ability to regulate their emotions and exert cognitive control over certain behaviors."

Researchers found that,  compared  with cocaine users given placebos - who (compared to healthy controls) exhibited reduced function in these prefrontal cortex regions - cocaine users given a low dose of methylphenidate had improved brain function such that they were more like the healthy control subjects. The subjects given methylphenidate were also less likely to make "errors of commission" (pressing a button incorrectly or prematurely), a measure of impulsivity, while performing the cognitive task than subjects given a placebo. Furthermore, the greater the improvement in task accuracy with methylphenidate, the larger the increase in fMRI signal in the prefrontal cortex regions of interest, showing that the improvements in brain function were directly related to improved cognitive performance.

Though future studies need to evaluate whether these results can be generalized to other tasks or activities that involve these specific brain regions, but these results do suggest that by enhancing prefrontal cortex function and associated cognitive performance - particularly the decrease in impulsivity - methylphenidate could help to improve clinical outcomes in people seeking to overcome drug addiction…

  

 Ref : http://www.pnas.org/content/early/2010/08/30/1011455107.full.pdf+html?sid=be34425f-b8cc-4a90-8929-03aca9f8bbe4

ESPAC-3 trial (Fluorouracil and Folinic Acid) shows promising results to prevent pancreatic cancer

In continuation of my update on  drug discovery and 5-fluorouracil

A major international trial has shown a commonly used chemotherapy drug, 5-fluorouracil, and  Folinic Acid  is as effective at helping prevent pancreatic cancer returning after surgery as the more expensive standard chemotherapy treatment.

The results of the Cancer Research UK- funded study mean the cheaper drug - called 5-fluorouracil (5-FU) - could be prescribed in cases when the standard chemotherapy - gemcitabine - has failed, providing an extra lifeline for patients whose cancer comes back after surgery.

They also raise hopes that a new trial currently underway, looking at combining an oral version of 5-FU with the standard treatment of gemcitabine, could lead to a more effective treatment for pancreatic cancer patients who are eligible for surgery.

The trial, called European Study Group for Pancreatic Cancer (ESPAC)-3, is the largest of its kind and involved 159 centres in Europe, Australasia, Japan and Canada which between them recruited 1088 patients who had undergone surgery for pancreatic cancer.

One group had the standard chemotherapy treatment - gemcitabine. The second group had a cheaper widely available drug called 5-fluorouralcil (5-FU) that is commonly used in cancer treatment already.

The results mean that 5-FU should now also be considered one of the standard options for the treatment of patients with this disease.

They build on earlier trial results suggesting patients who had surgery and chemotherapy had better a chance of survival than patients who only had surgery. 

Finding out these two drugs are as effective as each other at preventing pancreatic cancer returning after surgery is important. It raises hopes that a new trial currently looking at giving two similar drugs together could be successful at preventing or at least delaying pancreatic cancer returning after surgery.

"Previous trial results involving advanced pancreatic cancer patients have shown this drug combination can give precious extra months or even years of life, so there is reason to be hopeful the survival benefit could be even more marked for patients who are eligible for surgery."

 Ref : http://jama.ama-assn.org/cgi/content/full/304/10/1073

Study shows statin therapy not associated with cancer

Study shows statin therapy not associated with cancer

Scientists discover how omega-3 fatty acids shut down inflammation and reverse diabetes

(Picture, courtsey : Cell) Omega-3 fatty acids (-3 FAs), DHA and EPA, exert anti-inflammatory effects, but the mechanisms are poorly understood. Now the  researchers  show that the G protein-coupled receptor 120 (GPR120) functions as an -3 FA receptor/sensor. As per the claim by the researchers, stimulation of GPR120 with -3 FAs or a chemical agonist causes broad anti-inflammatory effects in monocytic RAW 264.7 cells and in primary intraperitoneal macrophages. All of these effects are abrogated by GPR120 knockdown. Since chronic macrophage-mediated tissue inflammation is a key mechanism for insulin resistance in obesity, researchers fed obese WT and GPR120 knockout mice a high-fat diet with or without -3 FA supplementation.

The -3 FA treatment inhibited inflammation and enhanced systemic insulin sensitivity in WT mice, but was without effect in GPR120 knockout mice. In conclusion, GPR120 is a functional -3 FA receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo by repressing macrophage-induced tissue inflammation. ….....

Ref : http://www.cell.com/fulltext/S0092-8674%2810%2900888-3

Berries can prevent age related brain degeneration: Study

Berries can prevent age related brain degeneration: Study