Encouraging results from first phase III clinical trials of Balaglitazone (an anti-diabetic drug)......

Balaglitazone (CAS-199113-98-9),5-[[4-[3-methyl-4-oxo-3,4-dihydro-2-quinazolinyl] methoxy]phenyl-methyl]thiazolidine-2,4-dione, (see structure) is a novel partial agonist of PPAR-gamma, which elicits only 52% of the PPAR-gamma activation observed with both pio- and rosiglitazone.

            

Pre-clinical studies have indicated that besides robust glucose lowering ability, balaglitazone results in lower body fluid accumulation, lower fat accumulation, less heart enlargement and no reduction of bone formation, indicating that Balaglitazone may be able to displace the balance between desired and side effects, and thus show a better safety profile than full agonists of PPAR-gamma.

 Now Reddy's Lab, has come up with interesting results from its  Phase III clinical trial programme.The study explored the impact of adding placebo, Balaglitazone 10mg, Balaglitazone 20mg or Pioglitazone 45mg to a background treatment regimen of stable insulin therapy for a period of 26 weeks. The primary endpoint was HbA1c reduction, while several secondary endpoints including fasting plasma glucose, oedema, weight gain, and body composition were considered.

In all, 409 patients were randomized in roughly equal proportions across the four arms of the study. All three active arms (Balaglitazone 10mg, 20mg and Pioglitazone 45mg) showed similar levels of efficacy with respect to both HbA1c and fasting plasma glucose.

All three active arms showed good tolerability and adverse event profile, with Balaglitazone 10mg demonstrating less water retention, less fat accumulation, lower weight/BMI gain and less bone loss when compared to the Pioglitazone arm.

Encourged by these results both companies (Dr. Reddy's & Rheoscience) are planning for detailed studies required for registration of  Balaglitazone.

Type 2 diabetes is a major cause of morbidity and mortality in the industrialized world, with cardiovascular disease as the leading cause of death, accounting for almost 50% of all T2D deaths. Furthermore, the number of T2D patients is increasing rapidly, and the number of patients is expected to reach between 300 and 380 million by 2025, thereby placing an enormous economical burden on global healthcare. Hope new drugs will take care of this problem.



Ref : http://www.drreddys.com/media/popups/jan4_2010.html

Brilinta (Ticagrelor) better than Plavix. ?.......

W knew that, Astra-Zeneca,  in its PLATO clinical trial in mid-2009,  found that ticagrelor had better mortality rates than clopidogrel (9.8% vs. 11.7%, p<0.001) in treating patients with acute coronary syndrome. Patients given ticagrelor were less likely to die from vascular causes, heart attack, or stroke but had slightly greater chances of major bleeding which was non-significant (11.6 vs. 11.2, p=0.4). Like clopidogrel and ticlopidine, ticagrelor blocks ADP receptors of subtype P2Y₁₂. In contrast to the other antiplatelet drugs, the blockage is reversible. Moreover, it does not need hepatic activation, which could reduce the risk of drug interactions-which makes it special.

Now this has been further substantiated by Dr. Chris. Cannon, who claims that  clot-busting drug Ticagrelor (Brilinta), may soon take the place of Clopidogrel (Plavix) in treating patients with acute coronary syndrome, which includes angina and heart attack.

In a new trial (by Dr. Christopher Cannon, a cardiologist with Brigham and Women's Hospital and an associate professor of medicine at Harvard Medical School, both in Boston), the upstart drug ticagrelor (Brilinta) reduced the risk of second heart attacks and death without raising the risk of bleeding, as clopidogrel (Plavix) can do and the authors claim  that this is pretty compelling evidence from this trial that ticagrelor is better without any increased risk of bleeding. 

In this study (funded by AstraZeneca) of more than 13,000 patients with acute coronary syndrome, Brilinta, appears to be more potent than Plavix and has  emerged with several advantages over the old standby  claims the researchers.

Brilinta is s processed as soon as it's swallowed (meaning it doesn't have to go through the liver), and kicks in faster than Plavix, where as Plavix (usually in combination with aspirin) has its share of problems, namely a lag time between when it is administered and when it takes effect, and variability in how different individuals respond to it. And because of an increased risk of bleeding, Plavix must be discontinued before surgery. Overall the researchers, claim that Brilinta has a more reliable level of anti-clotting effect. There's less variability. At the dose, it has about twice the level of anti-clotting effect and hence the  benefit in preventing heart attacks and stent thrombosis. The authors attribute the reason for the superiority of the drug to its quicker reversblity (than Plavix) and patients could have surgery with a lower risk of bleeding. FDA is expected to approve the drug late this year and  hope the patients with thrombosis, angina and acute coronary syndrome will breathe a sigh of relief...

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2962191-7/fulltext

BQCA improves symptoms of Alzheimer’s disease in rodents.....

The compound  benzylquinolone carboxylic acid (BQCA)  has been shown in earlier studies (rodent)  to lessen the occurrence and severity of the behavioral disturbances often symptomatic of Alzheimer's, such as hallucinations, delusions, paranoia and outbursts. But the important feature of this research lies in the fact that the compound, was able to change the way the brain works and whether or not it improved memory in our 'Alzheimer's mice,' which are experiencing progressive cognitive decline much like a person with Alzheimer's does.

Other attempts to identify such a specific treatment for Alzheimer's have failed, according to Dr.Michelle  Nicolle, the lead researcher. As per her claim "current treatments only treat the symptoms while the underlying disease is still progressing and  so recent research efforts are focusing on stopping disease progression instead of symptomatic treatment".

The researchers' findings suggest that  the compound BQCA,  could alter the progression of disease in mice and  ultimately  hold importance for humans as well.

BQCA activates a specific neurotransmitter receptor in the brain called the M1 muscarinic acetylcholine receptor. M1 receptors have been the focus of research into treatment of Alzheimer's disease because they affect the part of the brain that stimulates the memory and learning functions the disease inhibits. Until now, scientists have not found a treatment selective enough to activate the receptors without producing side effects such as nausea, vomiting and increased frequency of urination. As per the claim, BCQA is specific and BQCA also seemed to inhibit production of amyloid beta, one of the markers of Alzheimer's disease in the brain - perhaps key to the compound's potential for slowing the progression of the disease. Though detailed studies are still to be established its an interesting research. I found an interesting article in the same lines, those interested can read.

Ref : http://www.wfubmc.edu/News-Media-Resources/

Quercetin blocks Hepatitis C infection....

The conventional treatments for hepatitis C are interferon and ribavirin, which can cause major side effects and aren't effective in all patients. But something interesting and unique has been achieved  by UCLA researchers.

As per the claim by the lead researcher Samuel French Assistant Professor, Pathology of UCLA, they have  identified major two cellular proteins (HSPs, heat shock proteins 40 and 70) that play an important role in hepatitis C infection, and they say the finding may point to new and less toxic treatments for the disease, which can lead to cirrhosis and liver cancer. The researchers also found that Quercetin,  blocks the synthesis of two heat shock proteins 40 and 70proteins  and significantly inhibited viral infection in tissue culture.

 

Quercetin (see the structure) :  

Is a plant-derived flavonoid, specifically a flavonol, used as a nutritional supplement. Laboratory studies show it may have anti-inflammatory and antioxidant properties,  and it is being investigated for a wide range of potential health benefits.Interestingly American cancer society, says that while quercetin has been promoted as being effective against a wide variety of diseases, including cancer, There is current early-stage clinical research on quercetin addressing safety and efficacy against sarcoidosis, asthma and glucose absorption in obesity and diabetes. Food riches in Quercetin includes, capers, lovage, apples, tea (Camellia sinensis), onion, especially red onion (higher concentrations of quercetin occur in the outermost rings), red grapes, citrus fruit, tomato, broccoli and other leafy green vegetables, cherries and berries.

Significant claims by the researchers are ;

a. quercetin targets cellular proteins rather than viral proteins, there is less likelihood of developing viral

    resistance (cellular proteins cannot change like viral proteins can);

b. quercetin may allow for the dissection of the viral life cycle and has potential therapeutic use to reduce
    virus  production with low associated toxicity.

Hope the researcher will have positive results from the phase 1 clinical trial.....

Ref :http://www.cancer.ucla.edu/Index.aspx?page=644&recordid=312

Metformin - safe for patients with advanced heart failure and diabetes mellitus

In continuation of my update on Metformin,   I am sharing herewith  something interesting info,  about the same drug. Now researchers from David Geffen School of Medicine at UCLA,  have found that metformin, a drug often used in the treatment of diabetes mellitus, is safe for use in treating patients who have both diabetes and advanced heart failure. 

Diabetes increases not only the risk of developing heart failure, but also the risk of death among heart failure patients. This is due in large part to the fact that diabetes, because it increases the amounts of sugar and fat circulating in the bloodstream, accelerates the onset of coronary atherosclerosis. This hardening and thickening of blood vessels is the hallmark of atherosclerotic heart disease, the most common cause of death. The optimal treatment for high glucose and fat blood levels among heart failure patients has not been demonstrated.

The new study involved 401 patients of an average age of 56, with type II diabetes and advanced systolic heart failure. This patient cohort was followed for 14 years in a comprehensive heart failure management program.

The study results suggest that, in patients with both advanced heart failure and diabetes, use of metformin is safe, and may be associated with better heart failure survival.

Interestingly, the diabetes drug metformin previously carried a "black box warning" from the FDA against its use in treating diabetes in heart failure patients and that is why most many physicians have been reluctant to use metformin and other similar medications to treat this patient group. However, analysis by the researchars, shows that using metformin to treat diabetes in patients with advanced, systolic heart failure is not only safe, but may also play a role in improving outcomes compared to conventional diabetes care. As per the claim by Dr Gregg Fonarow, coresearcher,  metformin improves myocardial function via activation of a signaling mechanism (AMP-activated protein kinase) independent of antihyperglycemic effects. Together, these studies suggest that metformin may be cardioprotective by augmenting heart function at the molecular level, and should be further investigated as a treatment for heart failure, irrespective of diabetes....

Ref : http://www.newsroom.ucla.edu/portal/ucla/ucla-study-demonstrates-that-metformin-150497.aspx

DBZ an Alzheimer drug in clinical trails - a new hope for oesophageal cancer ?

Though there are some drugs for other cancers, but there is no good treatment, and sufferers for the cancer of  oesophagus  or gullet  and the patients  frequently face a short, painful battle which ends all too quickly in death. Many of the cancers diagnosed are in people with a long history of heartburn.

About Oesophagus cancer :

Chronic heartburn leads to the lower parts of the gullet being bathed in a toxic acid solution, and the lining of the gullet defends itself against this by changing itself into something which looks a lot like the lining of the lower intestines. Although the damaged tissue, called Barrett's oesophagus, is not cancerous in itself, its presence warns doctors that the patient has taken the first step towards cancer, and triggers a rigorous programme of monitoring, coupled with therapy to prevent further damage.

Patients with Barrett's oesophagus can be stabilised, and most do not go on to develop cancer, but once it is there, the mutated tissue is almost impossible to eradicate, so the risk always remains. Researchers have long been searching for new drugs able to revert Barrett's oesophagus to the healthy, normal lining of the gullet, and now, a team led by Hans Clevers of the Hubrecht Institute, Utrecht, have come up with a drug DBZ (see structure : source : Paul J. Ciaccio)  a drug already in clinical trails for the Alzheimer's disease.

The interesting part of this research is the basis for testing the drug. Clevers' team, whose research into colon cancer is world-renowned, reasoned that as Barrett's oesophagus cells are very similar to the cells which line the colon, they might share vital control pathways.

Clevers and his team then put this together with the fact that  the anti-Alzheimer's drug DBZ, currently in clinical trials, is known to have side effects on the lower gut lining. Researchers used a rat model of oesophageal cancer to observe the effects of DBZ on Barrett's oesophagus tissue, and found that DBZ could halt the growth of Barrett's oesophagus, and in some cases completely destroyed the mutant tissue. Whilst the treatment is still a long way from being trialled in humans, it is an exciting step forward in the fight for a cure for oesophageal cancer.

New hope for therapy in heartburn-related cancer is presented in the Research Article entitled 'Conversion of metaplastic Barrett's epithelium into post-mitotic goblet cells by gamma-secretase inhibition',

Hans Clevers et. al., Disease Models & Mechanisms (DMM), Vol3, Issue 1/2,

I found an interesting article in the similar lines, those interested can read at the link...

Pomegranates May Prevent Growth of Breast cancer cells.....

We know that Pomegranate aril juice provides about 16% of an adult's daily vitamin C requirement per 100 ml serving, and is a good source of vitamin B₅ (pantothenic acid), potassium and antioxidant polyphenols.  The most abundant polyphenols in pomegranate juice are the hydrolyzable tannins called punicalagins which have free-radical scavenging properties in laboratory experiments. Punicalagins are absorbed into the human body and may have dietary value as antioxidants. Other phytochemicals include polyphenols catechins, gallocatechins, and anthocyanins such as prodelphinidins, delphinidin, cyanidin, and pelargonidin.   Many food and dietary supplement makers have found advantages of using pomegranate phenolic extracts as ingredients in their products instead of the juice. One of these extracts is ellagic acid which may become bioavailable only after parent molecule punicalagins are metabolized. However, ingested ellagic acid from pomegranate juice does not accumulate in the blood in significant quantities and is rapidly excreted. Accordingly, ellagic acid from pomegranate juice does not appear to be biologically important in vivo.

Now researchers lead by Dr Shiuan Chen, director of the Division of Tumour Cell Biology, and Dr Lynn Adams, a research fellow at the centre's Beckman Research Institute have found that Pomegranates contain a group of compounds called ellagitannins ( glucosidesof elligacic acid) may prevent the growth of breast cancer cells. Researchers tried to determine whether chemicals in pomegranates could block the action of an enzyme called aromatase. Aromatase plays a key role in driving the growth of some forms of breast cancer by helping the body produce the female sex hormone oestrogen. Breast cancer drugs like anastrozole are designed to block its action.

The researchers screened ten ellagitannin-like compounds and found that one in particular, Urolithin B, (see above structure) significantly inhibited breast cancer cell growth in the laboratory. Its interesting to note that phytochemicals in pomegranates to exhibit this property (earlier the same authors have reported the inhibition of aromatase by grapes (phytochemicals).

Though further studies like in vivo are essential to further substantiate the in vitro studies (relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells) are essential (because of the fact that  the ellagitannins are not well absorbed into blood when provided in the diet), still in my opinion its a good finding......

^{Ref : http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/3/1/108}

Benefits of calcium and vitamin D in preventing fractures confirmed

Benefits of calcium and vitamin D in preventing fractures confirmed

Phentermine & Topiramate combination (Qnexa®) for obstructive sleep apnea (OSA)....

In continuation of my update on Qnexa® (combination of Phentermine & Topiramate), a drug by VIVUS, Inc., I found this info really interesting  to share with.

VIVUS, Inc on 7. January 201, announced positive results from a phase 2 study evaluating the safety and efficacy of Qnexa®, an investigational drug, for the treatment of obstructive sleep apnea (OSA). VIVUS recently completed phase 3 development of Qnexa for the treatment of obesity and submitted a New Drug Application (NDA) to the FDA for that indication. The OSA- study announced  demonstrated statistically significant improvement in the apnea/hypopnea index ("AHI" - a measure of the severity of sleep apnea) in patients with OSA treated with Qnexa for 28 weeks.

OSA is a sleep-related breathing disorder that involves a decrease or complete halt in airflow despite an ongoing effort to breathe. OSA is associated with an increased risk of hypertension, diabetes, stroke, sudden cardiac death and all-cause mortality. Currently, there are no approved pharmacologic treatments for OSA and current treatment approaches are limited to devices or surgery, so if approved by the FDA, Qnexa®  not only reduce the weight  but also significantly improve sleep apnea.

Ref : http://ir.vivus.com/releasedetail.cfm?ReleaseID=434708

NDA of Lurasidone for Schizophrenia...

In continuation of my update on  Lurasidone, ........

Dainippon Sumitomo Pharma America, Inc. (DSPA), a U.S. subsidiary of Dainippon Sumitomo Pharma Co., Ltd. (DSP), submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for lurasidone, an investigational atypical antipsychotic agent for the treatment of schizophrenia. The application, submitted on December 30, 2009, includes data from more than 40 clinical studies involving more than 2,500 lurasidone-treated patients.The efficacy of once-daily lurasidone was demonstrated in four six-week, placebo-controlled studies, involving hospitalized patients with schizophrenia. These studies included the global PEARL 1 and PEARL 2 clinical trials....

Ref : http://dsp-america.com/pdf/news/Lurasidone_NDA_Submission_PR_Jan_2010.pdf