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The Promise and Power of RNA

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People whose bodies make an unusually active form of a certain protein tend to have dangerously high levels of cholesterol. Those with an inactive form of the protein have low cholesterol and a low risk of heart attacks.


Needless to say, pharmaceutical companies would love to find a drug that can attach itself to the protein and block its activity. That might be difficult for this protein, which is called PCSK9. But a powerful new approach, called RNA interference, may surmount that obstacle. Instead of mopping up a protein after it has been produced, as a conventional drug would do, RNA interference turns off the faucet, halting production of a protein by silencing the gene that contains its recipe.


In monkeys, a single injection of a drug to induce RNA interference against PCSK9 lowered levels of bad cholesterol by about 60%, an effect that lasted up to three weeks. Alnylam Pharmaceuticals, the biotechnology company that developed the drug, hopes to begin testing it in people next year.

The drug is a practical application of scientific discoveries that are showing that RNA, once considered a mere messenger boy for DNA, actually helps to run the show. The classic, protein-making genes are still there on the double helix, but RNA seems to play a powerful role in how genes function.

“This is potentially the biggest change in our understanding of biology since the discovery of the double helix,” said John Mattick, a professor of molecular biology at the University of Queensland in Australia. And the practical impact may be enormous.

RNA interference, or RNAi, discovered only about 10 years ago, is attracting huge interest for its seeming ability to knock out disease-causing genes. There are already at least six RNAi drugs being tested in people, for illnesses including cancer and an eye disease. And while there are still huge challenges to surmount, that number could easily double in the coming year.

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Sources: The Times Of India

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Polypill for the Heart

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Sixty-five-year-old Virendra Mehta suffers from hypertension, diabetes and heart disease. Every day, he has to take 10 pills to keep his various ailm ents in check.

He finds it expensive and exhausting. ‘‘With so many medicines to take daily, I often forget which ones I have already taken. Besides incurring a huge expense, the sight of these medicines is also a constant psychological reminder that I’m unwell,’’ he says. For Mehta and many others, life would be much simpler if all the drugs they need to stay alive could be combined in a single pill.

This could happen soon. For the past few years, the Hyderabad-based Dr Reddy’s Laboratories has been working on a polypill that will combine four medicines used to treat heart disease – aspirin, (which acts as a blood thinner); two anti-hypertensives (to reduce blood pressure) and a statin (to lower lipid levels).

Researchers at Dr Reddy’s, one of the largest pharmaceutical companies in the country, say that the polypill will be that magic medical potion – cheaper than blockbuster drugs and more effective. For instance, the cost of a month’s medication of the polypill is likely to be less than Rs 100, almost one-third the cost of its component medicines if they’re taken individually.

Clinical trials of the pill have been completed in India and international trials have just started, using 400 patients from India, Australia, Brazil, Netherlands, New Zealand, UK and the US. Officials at Dr Reddy’s say that if all goes well, the pill should be ready for launch in India by next year.

The polypill, incidentally, is a deceptively simple concept. It is essentially a dream pill because it combines the properties of several drugs. But the problem lay in its execution. Anthony Rodgers of the University of Auckland, who is heading the ongoing clinical trials says,‘‘The biggest technical challenge was in getting all the four medicines in one pill, which needs to be a normal size and for its components to remain stable over a long period of time and produce the same effect on the body as if the medicines came from separate pills.’’

In fact,the idea of a polypill to prevent heart disease is just five years old. It was first suggested in the
authoritative British Medical Journal (BMJ) by two professors at London’s Wolfson Institute of Preventive Medicine, Nick J. Wald and Malcolm R. Law.

They claimed that such a pill could prevent 80% of all heart attacks and that anybody with cardiovascular disease could take it, as could everybody over 55. ‘‘It would be acceptably safe and with widespread use, would have a greater impact on the prevention of the disease in the Western world than any other single intervention,’’ they wrote.

Wald & Law’s claim set off intense debate within the medical fraternity about the viability of the polypill. The argument continues but most people agree that it might mean the difference between life and death for millions in developing countries, such as India, where heart disease is a bigger killer than cancer or AIDS. According to a WHO Global Burden of Disease study, there were 1.6 million deaths on account of heart disease in India in 2000. The National Commission on Macroeconomics and Health estimates that the number of Indians suffering from heart disease is set to grow to 62 million by 2015. The WHO adds that 17 million people die of heart disease and strokes every year and 80% of these deaths are in developing countries.

Clearly, a successful polypill could count on a vast market. That’s why, when the idea of the pill was suggested to Dr Reddy’s chairman, Dr Anji Reddy by Dr K Srinath Reddy, former head of cardiology, AIIMS, the company took it up with zest. G V Prasad, vice-chairman & CEO of Dr Reddy’s Labs, says ‘‘there will be significant demand for the polypill from those with heart disease or at high risk of developing it.’’ He says that heart disease is ‘‘globally the leading cause of death in developing and developed nations and will continue to remain so in the foreseeable future.’’

However, not everyone is optimistic. Dr Upendra Kaul, director of the cardiology department at Noida’s Fortis Hospital, says that a polypill does not necessarily help because it offers standard, rather than targeted medication. ‘‘How can you have a pill with fixed dosages of individual medicines to treat patients, when they might need different dosages, depending on their condition?’’ he asks. Many other critics of the polypill have also argued that this is its biggest drawback.

But Dr Reddy’s Labs says that it is working through the problem by manufacturing the polypill with different drugs of varying strength. ‘‘It should be suitable for a significant part of the patient population,’’ says Raghu Cidambi, who is anchoring the polypill project at Dr Reddy’s.

Adds Dr Ashok Seth of Max Devki Devi Heart and Vascular institute, ‘‘The polypill would be a good substitute for patients who have been on heart medication for long. Since their bodies would have adapted to these medicines, it would be easier to titrate their dosage by putting them on the polypill.’’

However, the polypill may still be many clinical trials away before it’s suitable for everyone. Initial trials have indicated that it successfully lowers BP and cholesterol in patients with established heart disease or those at high risk of developing it. But there’s still some way to go before the pill’s efficacy can be established for even those at moderate risk of heart attack.

In case the international trials are successful, says Rodgers, ‘‘it would be a landmark in cardiovascular disease prevention since we can then claim to have a product that can halve cardiovascular risk.’’ If that happens, it might just be a question of popping a pill to keep heart attack away.

Sources:The Times Of India

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New Anti-Cancer Compound Found

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A marine compound discovered off the coast of Key Largo in Florida inhibits cancer cell growth in lab tests and is likely to prompt the development of effective new drugs.

The University of Florida (UF)-patented compound, largazole, is derived from cyanobacteria that grow on coral reefs. It is being described as one of the most promising finds since the college’s marine lab was established three years ago.

The molecule’s natural chemical structure and its ability to inhibit cancer cell growth were first described in the Journal of American Chemical Society in February, and the lab synthesis and description of the molecular basis for its anti-cancer activity appeared on July 2.

“It’s exciting because we’ve found a compound in nature that may one day surpass a currently marketed drug or could become the structural template for rationally designed drugs with improved selectivity,” said Hendrik Luesch, assistant professor in UF’s Department of Medicinal Chemistry and the study’s principal investigator.

Largazole, discovered and named by Luesch for its Florida location and structural features, seeks out a family of enzymes called histone deacetylase, or HDAC. Overactivity of certain HDACs has been associated with several cancers such as prostate and colon tumours, and inhibition of HDACs can activate tumour-suppressor genes that have been silenced in these cancers.

Although scientists have been probing the depths of the ocean for marine products since the early 1960s, many pharmaceutical companies lost interest before researchers could deliver useful compounds because natural products were considered too costly and time-consuming to research and develop.

Many common medications, from pain relievers to cholesterol-reducing statins, stem from natural products that grow on the earth, but there is literally an ocean of compounds yet to be discovered in our seas.

Only 14 natural marine products developed are in clinical trials today, Luesch said, and one drug recently approved in Europe is the first-ever marine-derived anti-cancer agent.

“Marine study is in its infancy”, said William Fenical, professor of oceanography and pharmaceutical sciences at the University of California, San Diego. “The ocean is a genetically distinct environment and the single, most diverse source of new molecules to be discovered”.

HDACs are already targeted by a drug approved for cutaneous T-cell lymphoma manufactured by the global pharmaceutical company Merck & Co. Inc. However, UF’s compound does not inhibit all HDACs equally, meaning a largazole-based drug might result in improved therapies and fewer side effects, Luesch said.

Luesch said that, within the next few months, he plans to study whether largazole reduces or prevents tumour growth in mice. Luesch has several other anti-tumour natural products from Atlantic and Pacific cyanobacteria in the pipeline.

These results were presented on Thursday at an international natural products scientific meeting in Athens.

Sources: The Times Of Imdia

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