Washington, Nov 11 : Scientists from the Imperial College of London have found a promising drug for the treatment of an aggressive form of lung cancer.

The drug eliminated small cell lung cancer tumours in 50 percent of mice, and blocked the cells” ability to resist standard chemotherapy treatment.

The researchers are now planning to take the drug into clinical trials, to establish whether it could offer hope to patients with an inoperable form of lung cancer.

One in five people with lung cancer have small cell lung cancer and only three per cent of these people are expected to survive for five years.

In the new study, researchers identified drug that, in some mice, was able to completely shrink tumours away.

In the mouse models, the drug could stop tumours from growing and it helped other forms of chemotherapy to work more effectively.

If the drug proves successful in humans, researchers hope that it could help patients with this kind of lung cancer to live longer.

In small cell lung cancer, tumours spread quickly because the tumour cells grow and divide faster than normal cells.

In earlier research, the researchers showed that these tumour cells proliferate faster because they are fuelled by a growth hormone called FGF-2.

This growth hormone also triggers a survival mechanism in the tumour cells that makes them become resistant to chemotherapy.

In the current study, researchers looked at the effect of a drug called PD173074, which blocks the receptor that FGF-2 uses to attach to the tumour cells.

They found that the drug stopped cancer cells from proliferating and from becoming resistant to treatment in ”test-tube” laboratory models.

In one animal model of small cell lung cancer, the drug eliminated tumours in 50 percent of mice and in a second, similar mouse model, the drug enhanced the effect of standard chemotherapy.

“Our new research in mice suggests that it may be possible to develop the drug PD173074 into a new targeted therapy for small cell lung cancer. We hope to take this drug, or a similar drug that also stops FGF-2 from working, into clinical trials next year to see if it is a successful treatment for lung cancer in humans. An added bonus of this drug is that it could be taken orally, which would make it less invasive than some other forms of cancer therapy,” said Professor Michael Seckl, corresponding author of the study.

The study has been published in the journal Cancer Research.

Washington, Nov 5  : Scientists have identified a chemical cousin of the common antibiotic tetracycline that might be useful in treating spinal muscular atrophy (SMA), a currently incurable disease that is the leading genetic cause of death in infants.

The finding is based on a study conducted by Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory (CSHL) and scientists from Paratek Pharmaceuticals and Rosalind Franklin University of Medicine and Science.

SMA is caused by mutations in a gene called Survival of Motor Neuron 1 (SMN1), resulting in a decrease in the levels of SMN protein in the motor neurons of the spinal cord – the cells that control muscle activity.

Without the protein, these neurons degenerate, and infants born with the mutations progressively lose the ability to move, swallow, and breathe.

There are no approved therapies for the treatment of SMA.

The new molecule boosts the levels of SMN protein in cells by fixing a mistake in a cellular processing mechanism called RNA splicing.

In the study, the scientists report this fix in both mouse models of SMA, as well as in cells isolated from SMA patients.

Unlike previously identified molecules that stimulate SMN production, the tetracycline-like compound is a unique therapeutic candidate in that it is a small molecule that specifically alters RNA splicing by directly targeting the splicing reaction.

The research appears in the journal Science Translational Medicine.

London, Nov 4 (ANI): A new study of zebrafish has put scientists in the U.S. a step closer to unravelling the mechanism behind body part regeneration, a power possessed by some animals but not humans

The search for the holy grail of regenerative medicine—the ability to “grow back” a perfect body part when one is lost to injury or disease—has been under way for years, yet the steps involved in this seemingly magic process are still poorly understood.

Some animals like earthworms, crayfish and tadpoles perform this miraculous feat effortlessly, reports The Telegraph.

Scientists know the process involves mechanisms normally found in developing embryos, but are still not clear about what they are.

Now, the new study on zebrafish has helped scientists identify a key cellular pathway that appears to trigger regeneration by switching on certain genes.

“This is the first real molecular insight into what is happening during limb regeneration,” said lead author Dr Scott Stewart, from the Salk Institute in La Jolla, California.

“Until now, how amputation is translated into gene activation has been like magic. Finally, we have a handle on a process we can actually follow,” he added.

The researchers focused on a biological “priming” system that keeps embryonic cells ready to become whatever kind of tissue they are destined to be.

They found a particular enzyme, or biological catalyst protein, seemed to be crucial to the process.

The researchers now plan to take a closer look at the enzyme and find out how it operates.

They also intend to determine how the genes are switched off again once regeneration is complete.

London, Nov 2  : A novel computer program has identified thousands of new targets for existing drugs by comparing the molecular structures of drug compounds and chemicals that occur naturally in the body.

The technique could be used to uncover new applications or reveal potential side effects for drugs already on the market.

“It”s a new approach, and it”s a totally different from what everyone else has done. That”s why it actually works,” Nature quoted study author Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill as saying.

The most common methods for predicting whether a small molecule binds to various drug targets involves either high-throughput laboratory screening or virtually simulating whether a particular compound fits together with proteins like a key in a lock.

However, the experimental approach is tedious and time consuming, while the computational method relies on the existence of high-resolution protein structures, which are hard to come by for many drug-sensitive proteins.

Last year, German scientists developed a new approach for finding novel drug targets for existing medications by showing that drugs with similar adverse side effects often share a common target protein, even when those drugs are chemically quite different1.

In the new study, Roth and Brian Shoichet, a computational chemist at the University of California, San Francisco, have successfully identified new uses for marketed drugs by comparing existing drug compounds with different ligands – biologically active molecules that naturally bind proteins.

They thought that if a drug and ligand have similar three-dimensional structures, then there”s a good chance that the drug will bind to the same protein as the ligand.

The researchers” suspicions were proved correct.

They produced chemical ”fingerprints” of more than 3,600 drugs that were either approved or in late-stage clinical trials and some 65,000 ligands that together bind to around 250 protein targets.

They then developed a statistical technique to compare the two types of molecules and singled out nearly 7,000 pairs of predicted drug-target interactions, thousands of which had never been shown before.

The technique provides “a way of giving you decent molecular-based hypotheses for side effects of drugs and a way of looking for new targets for these very special molecules”, said Shoichet.

The study has been published in Nature

London, Oct 23 (ANI): Researchers at the University of Southampton have found that a dramatic rise in antidepressant prescriptions issued by GPs has been caused by a year on year increase in the number of people taking antidepressant drugs on a long-term basis.

They study showed that despite a drop in the number of new patients diagnosed with depression over 11 years, the number of prescriptions doubled.

“We estimate that more than 2 million people are now taking antidepressants long-term over several years, in particular women aged between 18 and 30,” said study’s lead author Tony Kendrick, a professor in Primary Medical Care of the University”s School of Medicine.

The number of prescriptions issued per patient rose from 2.8 in 1993 to 5.6 in 2004.

Prescription Pricing Authority data shows that more than 30 million prescriptions for SSRIs (selective serotonin reuptake inhibitors) such as Prozac and Seroxat, are now issued per year, twice as many as the early 1990s.

University of Southampton researchers found that 90 per cent of people diagnosed with depression are now taking SSRIs either continuously or as repeated courses over several years.

“Our previous research found that although these drugs are said not to be addictive, many patients found it difficult to come off them, due to withdrawal symptoms including anxiety. Many wanted more help from their GP to come off the drugs. We don”t know how many really need them and whether long-term use is harmful. This has similarities to the situation with Valium in the past,” Kendrick said.

For the study, the researchers analysed all new cases of depression between 1993 and 2005 from anonymous computerised general practice records covering 170 GP surgeries and 1.7 million registered patients.

The study has been published in the printed edition of British Medical Journal (BMJ).

Smarter inhaler design will enable more effective drug delivery to the lungs by minimising waste.
Current designs deliver only 10 to 20 percent of asthma medications to the lungs. As the lungs provide direct entry into the bloodstream, an optimised design will reduce drug waste.
“We were able to optimise a prototype mouthpiece that allowed for more medication to pass through the mouthpiece and be available to reach the lungs,” said Michael Hindle, research associate professor at Virginia Commonwealth University (VCU).
Hindle adds that this rational computational inhaler analysis and design approach, which was developed with Worth Longest from the School of Engineering at VCU, may be applicable for other inhalers and medications that require reproducible delivery.
“Insulin is an example of a drug that requires a reproducible delivery strategy that can be administered painlessly and as effectively through aerosol inhalers,” said Hindle, according to a VCU release.
The research will be presented in November at the American Association of Pharmaceutical Scientists Annual Meeting and Exposition.

UCLA scientists seem to have identified two chemicals which supposedly convince our cells to ignore premature signals in order to stop producing significant proteins.

Supposedly, the genetic disorders are caused by nonsense mutations. For instance, these nonsense mutations could perhaps affect nearly one in five patients with most genetic diseases.

Also, it may affect hundreds of thousands of people suffering from incurable diseases. Since, nonsense mutations could lead to cancer, such drugs may also prove beneficial in cancer treatment.

For the purpose of the study, the UCLA Molecular Shared Screening Resource center of the campus’s California NanoSystems Institute from the past four years seems to have screened approximately 35,000 chemicals in order to look for those which ignore premature stop signals.
“When DNA changes, such as nonsense mutations, occur in the middle rather than the end of a protein-producing signal, they act like a stop sign that tells the cell to prematurely interrupt protein synthesis. These nonsense mutations cause the loss of vital proteins, which can lead to deadly genetic disorders,” says Dr. Richard Gatti, professor of pathology and laboratory medicine and of human genetics at the David Geffen School of Medicine at UCLA.

Gatti’s lab is known to be specializing in studying ataxia-telangiectasia (A-T). A-T is a progressive neurological disease which appears to attack young children, often killing them by their late teens or early 20s.

Lead author of the study, Liutao Du, a postgraduate fellow in the UCLA Department of Pathology and Laboratory Medicine is believed to have developed the screening technology in Gatti’s laboratory.

Du further stated that, “Of the dozens of active chemicals we discovered, only two were linked to the appearance and function of ATM, the protein missing from the cells of children with A-T. These two chemicals also induced the production of dystrophin, a protein that is missing in the cells of mice with a nonsense mutation in the muscular dystrophy gene.”

The findings of the study may perhaps lead to novel medications for genetic diseases, such as cancer and muscular dystrophy. Apparently, they are sparked by missing proteins.

The UCLA team anticipates that their discovery may possibly assist pharmaceutical companies in creating drugs which correct genetic disorders.

The findings of the study have been published in the Journal of Experimental Medicine.

It is claimed that for the first time, researchers have illustrated that by apparently restraining the action of an enzyme known as TAK – 1, it may be likely to make pancreatic cancer cells sensitive to chemotherapy, thus creating an opportunity for the development of a new drug to treat the disease.

It was mentioned by Dr Davide Melisi that the resistance to chemotherapy was supposedly the biggest challenge to treat pancreatic cancer.

Dr Melisi, who until the start of September was a Fellow at the M.D. Anderson Center in Houston (Texas, USA); he has now moved to a staff position at the National Cancer Institute in Naples (Italy), commented, “Pancreatic cancer is an incurable malignancy, resistant to every anti-cancer treatment. Targeting TAK-1 could be a strategy to revert this resistance, increasing the efficacy of chemotherapy. During the past few years we have been studying the role played by a cytokine or regulatory protein called Transforming Growth Factor beta (TGFbeta) in the development of pancreatic cancer. Recently we focused our attention on a unique enzyme activated by TGFbeta, TAK-1, as a mediator for this extreme drug resistance.”

The expression of TAK-1 was apparently examined by Dr Melisi and his colleagues in pancreatic cell lines and apparently formed a drug that was supposedly able to slow down TAK-1. They claimed to test the activity of the TAK-1 inhibitor on its own and in alliance with the anti-cancer drugs gemcitabine, oxaliplatin and SN-38 which is claimed to be a metabolite of the anti-cancer drug irinotecan in cell lines, and the movement of the TAK-1 inhibitor apparently joined with gemcitabine against pancreatic cancer in mice.

Dr Melisi, mentioned, “The use of this TAK-1 inhibitor increased the sensitivity of pancreatic cells to all three chemotherapeutic drugs. By combining it with classic anti-cancer drugs, we were able to use doses of drugs up to 70 times lower in comparison with the control to kill the same number of cancer cells. In mice, we were able to reduce significantly the tumour volume, to prolong the mice survival, and to reduce the toxicity by combining the TAK-1 inhibitor with very low doses of a classic chemotherapeutic drug, gemcitabine, that would have been ineffective otherwise.”

The use of gemcitabine on its own against the cancer in mice was believed to be unsuccessful because of the drug resistant nature of the disease. Nevertheless, once it was joined with the TAK-1 inhibitor, an approximate 78% drop in tumor volumes was observed by Dr. Melisi and colleagues.

Dr. Melisi remarked, “The median average survival for the control, TAK-1 inhibitor, gemcitabine on its own, or TAK-1 inhibitor combined with gemcitabine was 68, 87, 82 and 122 days respectively.”

Dr. Melisi further quoted, “This is the first time that TAK-1 has been indicated as a relevant target for the treatment of a solid tumour and that it is a valid approach to reverting the intrinsic drug resistance of pancreatic cancer. The TAK-1 inhibitor used in this study is an exciting drug that warrants further development for the treatment of pancreatic cancer. In the near future, we will study whether it is also able to make other chemotherapeutic agents, such as oxaliplatin, 5-FU or irinotecan, work against pancreatic cancer in mice.”

Dr. Melisi mentioned that their main goal is to translate this combination approach from the bench to the bedside, conducting a clinical trial that could demonstrate the safety of this TAK-1 inhibitor in combination with gemcitabine, and its efficacy, in pancreatic cancer patients.

This was put forth by Melisi in Europe’s Cancer Congress, ECCO 15 – ESMO, Berlin.

Women who take certain antidepressants during the first three months of pregnancy may have a slightly increased risk of giving birth to babies with heart defects.

Septal heart defects — malformations in the wall separating the right side of the heart from the left — were more common among women taking antidepressants in the first trimester, Danish researchers found. Some of these heart defects resolve on their own, while others require surgery.

The risks were seen in sertraline (trade names Zoloft and Lustral) and in citalopram (Celexa), both of which belong to the class of medications known as selective serotonin reuptake inhibitors (SSRIs).

Women who took more than one SSRI early in their pregnancy had a fourfold higher risk of having babies with this problem, said the authors of a study appearing online Sept. 24 in BMJ.

Still, the authors said the absolute risk is relatively low: 246 women would have to take such medication in order to see one septal heart defect. And 62 mothers would have to take more than one SSRI to see a problem in one child.

“A potential association with malformations must be considered in the choice of treatment of depression during pregnancy,” said Dr. Lars Henning Pedersen, lead author and a research assistant in the department of epidemiology at Aarhus University in Denmark. However, “if our data is correct, the absolute risk is low, which must be balanced against the potential substantial risk of under- or untreated depression during pregnancy.”

Other experts agree. “Early exposure can slightly increase the risk of heart defects, but the overall risk is still very, very small,” added Dr. Jennifer Wu, an obstetrician and gynecologist at Lenox Hill Hospital in New York City.

And discontinuing antidepressants also carries risks.

“The concern with pregnant women with depression, if you take them off their medication, they can have a relapse into severe depression and this could lead to self-destructive behaviors,” Wu said.

Previous studies have found that pregnant women who stopped taking their antidepressant medications were five times more likely to relapse than women who continued with the medication.

In the United States, 13 percent of women have taken an antidepressant while pregnant, according to an accompanying editorial.

Recent research has indicated a higher risk of various defects, including heart defects, among pregnant women taking antidepressants, and the U.S. Food and Drug Administration and the American College of Obstetricians and Gynecologists (ACOG) have issued warnings about possible birth defects associated with the use of the SSRI Paxil (paroxetine) by moms-to-be.

But existing studies have yielded conflicting results about dangers associated with specific drugs.

These researchers looked at almost 500,000 children born in Denmark between 1996 and 2003, a time when the number of pregnant women taking antidepressants quadrupled.

Although no overall association was found in this study between mothers taking SSRIs during the first trimester and birth defects in general, there was a doubling in the risk for septal heart defects for women using Zoloft and Celexa, but not Prozac (fluoxetine) or Paxil.

Pedersen recommended more and larger studies to explore the matter.

In August, the American Psychiatric Association in collaboration with ACOG recommended that women with major depression who are pregnant or planning to get pregnant can start or continue with antidepressant drugs, while women who choose to stop taking the drugs should consider psychotherapy.

“Ideally, you’d want to work closely with a psychiatrist and ob/gyn when planning a pregnancy,” Wu said. “When you are suddenly pregnant, there’s a lot of anxiety involved and other hormones, so it’s probably not a good time at that point to try to go off medications, and it certainly should be supervised.”

Patients who are relatively stable, on the other hand, could consider going off their medications for the first trimester, knowing that it will take four-to-six weeks for the drug effect to wear off and also knowing that the medications would be resumed at the first sign of a relapse, Wu said.

Source: http://womenshealth.gov/faq/depression.cfm

A new drug for people whose high blood pressure cannot be controlled by existing medications has done well in a pivotal trial, researchers report.

Substantial reductions in blood pressure were achieved with various doses of the drug, darusentan, for people who were still hypertensive despite trying three or more medications, said a report released online Sept. 13 in The Lancet.

An effective new drug against resistant high blood pressure could be “potentially enormously beneficial,” said one expert, Dr. Kirk Garratt, clinical director of interventional cardiovascular research at Lenox Hill Hospital in New York City.

The blood pressure drops seen in the study are highly encouraging, Garratt said. “It only takes small changes in blood pressure readings to confer benefits on patients,” he noted. “This drug potentially takes people from a very dangerous place to a very safe place.”

The study results will be submitted to the U.S. Food and Drug Administration as part of an application for marketing approval, said Nathan Kaiser, a spokesman for Gilead Sciences, the company that is developing the drug.

“A larger trial completed enrollment earlier this year,” Kaiser said. “We expect data from that trial by the end of the year. Pending results of that second study, the earliest time we can apply for approval appears to be the fourth quarter of 2010.”

Some studies have said that as many as 30 percent of people with high blood pressure, a major risk factor for cardiovascular problems such as heart attack and stroke, have the resistant form, in which blood pressure cannot be brought down to desired levels despite use of three or more drugs.

Darusentan acts to block the activity of endothelin, an artery-narrowing molecule. Its action involves a different molecular pathway than those targeted by conventional blood pressure medications, such as calcium channel blockers and diuretics.

The study, done at 117 sites across the globe, enrolled 379 people with systolic blood pressure (the higher number in a reading) that remained at 140 or higher (130 for those with diabetes or chronic kidney disease). The recommended blood pressure reading is 120/80. All patients received 14 weeks of treatment with daily doses of 50, 100 or 300 milligrams of darusentan, or a placebo, an inactive substance.

On average, the participants’ systolic blood pressure dropped 17 points with the 50-milligram dose of darusentan and 18 points with both the 100-milligram and the 300-milligram dose. A 9-point drop was recorded in the placebo group.

“That was a very meaningful reduction in blood pressure,” said study lead author Dr. Michael A. Weber, professor of medicine in the cardiology division of State University of New York, Downstate College of Medicine. “Even if you subtract what happened in the placebo group, you still get about a 10-point drop, which is a clinically important finding. It translates into a meaningful reduction in the likelihood of strokes and other cardiovascular outcomes.”

The major side effect was edema, excess fluid accumulation, which occurred in 27 percent of people taking the active drug and 14 percent of those taking placebo.

Because of edema, “to be really effective, darusentan probably should be used along with effective diuretic therapy,” Weber said. Diuretics, which increase the flow of fluid from the body, are already widely used against high blood pressure.

If darusentan works as hoped, it will be especially useful for older people with resistant high blood pressure, Weber said. “They tend to be middle-aged or older, often with some impairment of kidney function,” he said. “It is harder and harder to treat them and even more necessary to get their blood pressure treated, so new and more effective tools will be even more valuable.”

More information
There’s more on resistant high blood pressure at the American Heart Association.