Cholesterol Drug Vytorin Linked to Reduced Heart Attack Risk

We know that, Ezetimibe/simvastatin  is a drug combination used for the treatment of dyslipidemia. It is a combination of ezetimibe (known as Zetia in the United States and Ezetrol elsewhere) and the statin drug simvastatin (known as Zocor in the U.S.). The combination preparation is marketed by Merck & Co. under the trade names Vytorin and Inegy. Ezetimibe reduces blood cholesterol by acting at the brush border of the small intestine and inhibiting the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver.

Simvastatin is an HMG-CoA reductase inhibitor or statin. It works by blocking an enzyme that is necessary for the body to make cholesterol.

New Cholesterol-Lowering Drug, ALN-PCS Shows Early Promise

An experimental drug that lowers LDL "bad" cholesterol by helping sweep it from the bloodstream appears to be both safe and effective in its first human trial.

The drug known as ALN-PCS reduced cholesterol an average of 40 percent in the small, early study, and, if proven to work in large trials, potentially could replace or complement statins, the researchers said.

Currently, statin drugs such as Lipitor, Crestor and Zocor are widely used to control cholesterol. One heart doctor not involved with the new study said another class of drugs might be useful.

"Cardiovascular disease remains the leading cause of death of men and women globally and reduction of LDL cholesterol with statin medications has been demonstrated to substantially reduce the risk of first or recurrent cardiovascular events," said Dr. Gregg Fonarow, a professor of cardiology at the University of California, Los Angeles.

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61914-5/abstract

New Cholesterol-Lowering Drug Shows Early Promise - Drugs.com MedNews

FDA Approves Merck’s Liptruzet (ezetimibe and atorvastatin), a New Product That Can Help Lower LDL Cholesterol

In continuation of my update on ezetimibe and atorvastatin
FDA Approves Merck’s Liptruzet (ezetimibe and atorvastatin), a New Product That Can Help Lower LDL Cholesterol

FDA Approves Juxtapid - New Orphan Drug for Rare Cholesterol Disorder

In continuation of my update on Juxtapid (lomitapide) 

We know that, Lomitapide (INN) is an investigational drug for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals.  It has been tested in several Phase II clinical trials as single treatment and in combinations with atorvastatin, ezetimibe and fenofibrate. 

The US Food and Drug Administration approved lomitapide on December 21, 2012 as anorphan drug to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in patients with homozygous familial hypercholesterolemia (HoFH).

FDA Approves Juxtapid - New Orphan Drug for Rare Cholesterol Disorder

First combination drug to treat type 2 diabetes and high cholesterol receives FDA approval

In continuation of my update on Simvastin

The U.S. Food and Drug Administration recently approved Juvisync (sitagliptin and simvastatin), a fixed-dose combination (FDC) prescription medication that contains two previously approved medicines in one tablet for use in adults who need both sitagliptin and simvastatin.....

More....

Bear bile chemical could help keep hearts in rhythm

We know that, the compound, ursodeoxycholic acid (UDCA, see structure), is already used to lower cholesterol and help dissolve gallstones, and it's a key ingredient in many traditional Chinese medicines, which use bear bile. According to the latest research from Imperial College London it might also be able to treat abnormal heart rhythm, or arrhythmia, in fetuses and heart attack victims.

“These findings are exciting because the treatments we have now are largely ineffective at preventing arrhythmia in patients who develop an abnormal heart rhythm after a heart attack,” said Dr. Julia Gorelik...........

Ref : http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_2-8-2011-10-25-30

Experimental drug raises 'good' cholesterol, may help control diabetes

Experimental drug raises 'good' cholesterol, may help control diabetes

Cholesterol's Other Way out ....

Researchers lead by Mark Brown of Wake Forest University School of Medicine, have come up with an interesting finding that is "there is more than one way to get rid of that cholesterol, which can otherwise lead to atherosclerosis and heart disease".

A model of cholesterol loss first proposed way back in the 1920s suggested the existence of a route that didn't rely on bile. And indeed, studies in dogs unable to get cholesterol into bile showed that the animals actually experienced an increase in cholesterol loss. More recent studies in mice showed a similar thing.  Even so, the researchers said that an alternative pathway has largely been ignored. As a result, scientists have made very little progress in defining the molecular pathways and players involved.

Now, Brown and his colleagues offer new evidence that helps support and clarify this alternate path for cholesterol. Researchers report that mice made unable to secrete cholesterol into bile through genetic manipulation or surgery still lose cholesterol through the feces at a normal rate. Macrophages in those animals also continued to take up cholesterol from blood vessels. The researchers believe that alternate path delivers cholesterol from the liver to the intestine directly through the bloodstream.

     "The classic view of reverse cholesterol transport involved the delivery of peripheral cholesterol via HDL to the liver for secretion into bile," the researchers wrote. "In parallel, we believe that the liver also plays a gatekeeper role for nonbiliary fecal sterol loss by repackaging peripheral cholesterol into nascent plasma lipoproteins that are destined for subsequent intestinal delivery."

For the purposes of cholesterol-lowering drug discovery, it may prove fruitful to consider those two pathways as "separate and compel", claims the lead researcher.

Researchers claims that the drugs aimed to increase cholesterol loss without relying on bile will have fewer side effects (an excess of cholesterol in bile can lead to gallstones). Let us be optimistic and hope for the best, in the near future...

Ref : http://www.cell.com/cell-metabolism/abstract/S1550-4131%2810%2900186-5

Flaxseed lowers high cholesterol in men.....

Flax (also known as common flax or linseed) (Linum  usitatissimum) is a member of the genus Linum in the family Linaceae. It is native to the region extending from the eastern Mediterranean to India.  This is called as Agasi/Akshi in Kannada, Jawas/Javas (जवस) or Alashi (अळशी) in Marathi.  

Flax seeds come in two basic varieties brown yellow or golden. Most types have similar nutritional characteristics and equal amounts of short-chain omega-3 fatty acids. The exception is a type of yellow flax called Linola or solin, which has a completely different oil profile and is very low in omega-3. Although brown flax can be consumed as readily as yellow, and has been for thousands of years, it is better known as an ingredient in paints, fiber and cattle feed. Flax seeds produce a vegetable oil known as flaxseed or linseed oil, which is one of the oldest commercial oils and solvent-processed flax seed oil has been used for centuries as a drying oil in painting and varnishing. 

Flaxseeds are rich in alpha linolenic acid (ALA), an omega-3 fat that is a precursor to the form of omega-3 found in fish oils called eicosapentaenoic acid or EPA. Many benefits like 1. anti-iflammatory benefits, 2. omega-3-rich flaxseeds protect bone health, 3.protection against heart disease, cancer and diabetes, 4. flaxseeds help prevent and control high blood pressure. And even it helps to control some types of cancers.

Earlier report says,  Flaxseed provides comparable cholesterol-lowering benefits to statin drugs. Now this has been further substantiated by researchers from Iowa State University's (ISU) Nutrition and Wellness Research Center (NWRC).

Suzanne Hendrich, an ISU professor in food science and human nutrition, led a study that examined the effects of flaxseed lignan in 90 people diagnosed with high cholesterol. The results showed that consuming at least 150 milligrams of flaxseed lignans per day (about three tablespoons) decreased cholesterol in men, but not women, by just under 10 percent over the three months that they were given the flaxseed.  Suzanne concludes that though the result is  considerably less than the expected outcome from cholesterol-lowering drugs -- approximately 10 to20 percent for three months, depending on the individual -- it's still enough to make flaxseed a more natural option for some men. While the study found that the flaxseed lignans lowered cholesterol in men, it did not produce a significant change in women. More.... 

Ref : http://www.news.iastate.edu/news/2010/mar/flaxseed

(Those interested in knowing the other benefits of flax seed can read the article..)

Eprotirome a promising addition to statin therapy ?

People with bad cholesterol have  risk of  future heart disease,  despite  cholesterol-lowering statin therapy. Now researchers from  Johns Hopkins have come up with interesting finding i.e.,  a drug that mimics the action of thyroid hormone [Eprotirome (new generic name for KB2115) structure source : chemBlink)  lowered cholesterol up to 32 percent in those already on statins, an effect equal to that expected from doubling the statin drug doses, without harmful side effects. 

Interestingly, the researchers caution that the results don't suggest that eprotirome will or should replace statins, which are the current gold standard for treating high LDL cholesterol.

However, the results of their small trial on 168 patients do suggest that eprotirome may eventually be a promising addition to statin therapy, a substitute for statins in people who can't tolerate their side effects, or a novel treatment for mixed dyslipidemia, a condition in which people have high levels of lipids other than cholesterol such as triglycerides or apolipoprotein B (apo B).

The researchers found that among the patients taking the 25, 50 or 100 mg doses of eprotirome reduced their LDL cholesterol levels by 22 percent, 28 percent, and 32 percent respectively, compared to only 6.5 percent in those taking placebo. Remarkably, they also found similar dose-related reductions in triglycerides, apo B, and Lp(a). They also found modest reductions in HDL cholesterol of approximately 3 percent.

As per the claim by the lead researcher Dr. Paul W. Ladenson,   'this drug represents a new class of medications that might offer hope to those at risk of future cardiovascular disease whose lipid profiles are not effectively altered with statin therapy, and perhaps for about a quarter of those who have tried statins but cannot tolerate their side effects'. Dr. Ladenson is a consultant to Karo Bio, maker of eprotirome.......

Ref : http://content.nejm.org/cgi/content/short/362/10/906

Simvastatin prevents progression of Parkinson's Disease ?

About Simvastin :
Simvastatin, (marketed under the names Zocor, Simlup, Simcard, Simvacor) is a hypolipidemic drug belonging to the class of pharmaceuticals called "statins". It is used to control hypercholesterolemia and to prevent cardiovascular disease. Simvastatin is a synthetic derivate of a fermentation product of Aspergillus terreus. When I was working with Bangalore based company, the sister company was working on it and now its marketing too.

Recently researchers from the Rush University, have found an interesting fact that Simvastin, may prevent Parkinson's disease from progressing further. The authors have shown that the activity of one protein called p21Ras is increased very early in the midbrain of mice with Parkinson's pathology. Simvastatin enters into the brain and blocks the activity of the p21Ras protein and other associated toxic molecules, and goes on to protect the neurons, normalize neurotransmitter levels, and improves the motor functions in the mice with Parkinson's.

If the researchers are able to replicate these results in Parkinson's patients in the clinical setting, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease. Hope some relief to the sufferers of Parkinson disease....

Ref : http://www.rush.edu/webapps/MEDREL/servlet/NewsRelease?id=1304

Lovastatin-synthesizing enzyme successfully reconstituted...

Lovastatin is a member of the drug class of statins, used for lowering cholesterol (hypolipidemic agent) in those with hypercholesterolemia and so preventing cardiovascular disease. Lovastatin is a naturally occurring drug found in food such as oyster mushrooms and red yeast rice. When I was working with a Banglore based company (Biocon), they did try this compound and I think the company is marketing this drug now. As for as my knowledge goes there were two ways to synthesise 'biosynthesis using Dield-Alder catalyzed cyclization' & 'biosyntheis using broadly specific acyltransferase'

Dield-Alder catalysed cyclisation : In vitro formation of a triketide lactone using a genetically-modified protein derived from 6-deoxyerythronolide B synthase has been demonstrated. The stereochemistry of the molecule supports the intriguing idea that an enzyme-catalyzed Diels-Alder reaction may occur during assembly of the polyketide chain. It thus appears that biological Diels-Alder reactions may be triggered by generation of reactive triene systems on an enzyme surface.

Biosynthesis using broadly specific acyltransferase : It has been found that a dedicated acyltransferase, LovD, is encoded in the lovastatin biosynthetic pathway. LovD has a broad substrate specificity towards the acyl carrier, the acyl substrate and the decalin acyl acceptor. It efficiently catalyzes the acyl transfer from coenzyme A thoesters or N-acetylcysteamine (SNAC) thioesters to monacolin J. The biosynthesis of lovastatin is coordinated by two iterative type I polyketide syntheses and numerous accessory enzymes. Nonketide, the intermediate biosynthetic precursor of lovastatin, is assembled by the upstream megasynthase LovB (also known as lovastatin nonaketide synthase), enoylreductase LovC, and CYP450 oxygenases.

Recently more interesting out come from a group of UCLA researchers is that, for the first time thy have successfully reconstituted in the laboratory the enzyme responsible for producing the blockbuster cholesterol-lowering drug lovastatin. As per the claim by the researchers, the lovastatin-synthesizing enzyme is one of the most interesting but least understood of the polyketide synthases, which are found in filamentous fungi and which play a crucial role in the synthesis of "small molecule natural products" — pharmacologically or biologically potent compounds produced by living organisms, many of which are the active ingredients in pharmaceuticals.

This finding is of great significance because commonly used antibiotics, such as tetracycline, are produced by polyketide synthases. Polyketides represent a class of 7,000 known structures, of which more than 20 are commercial drugs, including the immunosuppressant rapamycin, the antibiotic erythromycin and the anticancer drug doxorubicin. In their study studied the enzyme that makes a small-molecule precursor to lovastatin. The real difference about this enzyme, is its extraoridnarily large size in comparison to all other enzymes so for studied. As per the claim by the lead researcher Dr. Yi Tang, "It's one of the largest enzymes ever to be reconstituted in a test tube. It is 10 times the size of most enzymes people study & the enzyme has seven active sites and catalyzes more than 40 different reactions that eventually result in an important precursor to lovastatin. Hope with this remarkable achievement, one can prepare many natural products in the lab in the days to come.

Ref : http://www.newsroom.ucla.edu/portal/ucla/ucla-engineering-researchers-have-111812.aspx