DRDO’s Dengue-killer headed abroad while country suffers

A potent Dengue-busting formulation developed by the Defence Research & Development Organisation (DRDO) almost a decade ago is headed to Brazil and Mexico without its benefits being felt anywhere in India.
The Central Insecticides Board & Registration Committee (CIBRC) has disallowed the use of this formulation – known as ‘mosquitocidal trap – within India for want of reams of data by the DRDO pertaining to its efficacy, although trials conducted with help of Delhi Municipal Corporation limits between 2008 and 2010 proved to be not just effective but also environment-friendly and cost effective. The device, said to resemble a paint spray gun, is estimated to cost just Rs 100 a piece with the formulation.
However, the same CIBRC has allowed the formulation to be exported through a Mumbai-based company named Alkyl Amines, which is looking at – and is most likely to – finding buyers in Brazil and Mexico.
Sources in DRDO told Bangalore Mirror that delivering the data as asked by CIBRC would run up costs to “crores of rupees” as the studies, researches and field trials would have to be conducted over many more years to prove the efficacy of this formulation. “There problems of funding as far as this is concerned,” said a senior DRL scientist.
Instead, and unfortunately, he said the Mumbai-based private company is in a position to do that abroad in collaboration with companies there.
This is the sad state of affairs in a country which has been found by an international study, to be grossly under-reporting Dengue cases with the actual number of cases at a shocking 282 times that of the official figures.
Two agencies under the DRDO umbrella – Tejpur-based Defence Research Laboratory (DRL) and Gwalior-based Defence Research & Development Establishment (DRDE) –developed the lure-and-kill formulation in 2005-06 that attracted female Aedes aegypti and Aedes albopictus mosquitoes (the ones spreading Dengue through their bites) to lay eggs in predetermined stagnant waters. These eggs hatch into larvae but do not transform into adults as the insecticide component of the formulation destroy the larvae.
The advantage of this technology is that one can actually choose where the female mosquitoes can lay eggs (as long as still water exists) and then ensure the destruction of the larvae.
To achieve this, the DRL and DRDE scientists replicated the natural pheromones emitted by the female mosquitoes which send signals to subsequent egg-laying females to settle in those waters to lay their eggs. Pheromones are chemical substances naturally produced and released into the environment by mammals or insects to allow other of its species to do the same things as earlier done by them.
In this case, the scientists replicated the pheromones using cuticular hydrocarbons found on the mosquito’s body surface, which acted as the natural pheromones. These acted as beacons to ‘invite’ the female mosquitoes to lay eggs in particular water-based locations – only for the subsequent larvae to be destroyed.
DRDO scientists fittingly call it a kill-at-source solution to the dreaded disease, which can also develop into the Dengue Haemorrhagic Fever (DHF), a fatal condition.
Dr Vijay Veer, director, DRL, confirmed to Bangalore Mirror: “Alkyl Amines in Mumbai has this technology (through transfer of technology from DRDO) and got CIBRC permission to export. (But) CIB permission for use in India is not available.”
Dr Veer said DMC had discussions with DRDO about procuring the mosquitocidal trap six years ago so it could out the spray to good use to completely eradicate the disease. But the CIBRC prohibition has put paid those efforts.
Some hope has come through the office of the Director General of Life Sciences, DRDO, in Delhi. Officials, who did not want to be named, said the mosquitocidal trap would continue to be improved in the DRDE and DRL labs over the next few years. The scientists have not given up. They are trying their best to meet the CIBRC requirements so this will be available to people in this country to eliminate Dengue.
The urgency surrounding this is mainly because an international study has sounded an alarm over the way Dengue is being managed in India by the government bodies. The study Economic and disease burden of Dengue in India published in American Journal of Tropical Medicine and Hygiene in October 2014 has proved with evidence that between 2006 and 2012 the annual average number of Dengue cases in the country was 57,78,406 as against the mere 20,474 cases given out by the National Vector Borne Disease Control Programme – 282 times the official figure.
The study has fixed India’s Dengue burden as US$ 1.1 billion per year from the medical costs as well as the income per man lost due to the disease.

"Imaginary meal" tricks the body into losing weight

Salk scientists made a more effective diet pill

Salk researchers have developed an entirely new type of pill that tricks the body into thinking it has consumed calories, causing it to burn fat. The compound effectively stopped weight gain, lowered cholesterol, controlled blood sugar and minimized inflammation in mice, making it an excellent candidate for a rapid transition into human clinical trials.
Unlike most diet pills on the market, this new pill, called fexaramine, doesn’t dissolve into the blood like appetite suppressants or caffeine-based diet drugs, but remains in the intestines, causing fewer side effects.
"This pill is like an imaginary meal," says Ronald Evans, director of Salk’s Gene Expression Laboratory and senior author of the new paper, published January 5, 2014 in Nature Medicine. "It sends out the same signals that normally happen when you eat a lot of food, so the body starts clearing out space to store it. But there are no calories and no change in appetite."


Ronald Evans, director of Salk’s Gene Expression Laboratory, has developed a compound called fexaramine that acts like an imaginary meal. Fexaramine, which tricks the body into reacting as if it has consumed calories, could lead to an effective obesity and diabetes treatment in humans. Image: Courtesy of the Salk Institute for Biological Studies


In the United States, more than a third of adults are obese and 29.1 million people have diabetes, according to the Centers for Disease Control and Prevention. Both obesity and diabetes lead to an increase in health spending, a greater risk of health complications and a shorter lifespan.
Evans’ laboratory has spent nearly two decades studying the farensoid X receptor (FXR), a protein that plays a role in how the body releases bile acids from the liver, digests food and stores fats and sugars. The human body turns on FXR at the beginning of a meal, Evans and others have shown, to prepare for an influx of food. FXR not only triggers the release of bile acids for digestion, but also changes blood sugar levels and causes the body to burn some fats in preparation for the incoming meal.
Pharmaceutical companies aiming to treat obesity, diabetes, liver disease and other metabolic conditions have developed systemic drugs that activate FXR, turning on many pathways that FXR controls. But these drugs affect several organs and come with side effects. Evans wondered whether switching on FXR only in the intestines–rather than the intestines, liver, kidneys and adrenal glands all at once–might have a different outcome.
"When you eat, you have to quickly activate a series of responses all throughout the body," says Evans. "And the reality is that the very first responder for all this is the intestine."
Evans and his colleagues developed the fexaramine compound by departing from the drug scaffold that most pharmaceutical companies typically pursue when targeting FXR. "It turns out that when we administer this orally, it only acts in the gut," explains Michael Downes, a senior staff scientist at Salk and co-corresponding author of the new work. Giving one such drug in a daily pill form that only reaches the intestines–without transporting into the bloodstream that would carry the drug throughout the body–not only curtails side effects but also made the compound better at stopping weight gain.
When the group gave obese mice a daily pill of fexaramine for five weeks, the mice stopped gaining weight, lost fat and had lower blood sugar and cholesterol levels than untreated mice. In addition, the mice had a rise in body temperature–which signals metabolism ramping up–and some deposits of white fat in their bodies converted into a healthier, energy-burning beige form of the tissue. Even the collection of bacteria in the guts of mice shifted when they received the drug, although what those changes mean isn’t clear yet.

Salk researchers demonstrated that fexaramine stops weight gain and burns fat in animal models. Fexaramine is only absorbed in the gut and does not go into the bloodstream, so it does not cause side effects common for typical diet pills. After additional testing, researchers believe this will lead to an effective weight loss diabetes treatment for humans. (Image: Courtesy of the Salk Institute for Biological Studies)

So, why does fexaramine in the intestines work even better than drugs that simultaneously activate FXR throughout the body? Evans thinks it has to do with the natural order in which the body’s molecular pathways normally responds to a meal.
"The body’s response to a meal is like a relay race, and if you tell all the runners to go at the same time, you’ll never pass the baton," says Evans. "We’ve learned how to trigger the first runner so that the rest of the events happen in a natural order."
Since fexaramine doesn’t reach the bloodstream, it is also likely safer in humans than other FXR-targeting drugs, the researchers hypothesize. They’re already working to set up human clinical trials to test the effectiveness of fexaramine to treat obesity and metabolic disease. Ideally the drug, administered under a doctor’s guidance, would work in conjunction with diet and lifestyle changes, similar to weight-loss surgeries or other obesity or diabetes drugs.

From left: Salk researchers Ruth Yu, Sungsoon Fang, Annette Atkins, Ronald Evans, Michael Downes and Sandra Jacinto (Image: Courtesy of the Salk Institute for Biological Studies)

Other researchers on the study were Sungsoon Fang, Jae Myoung Suh, Elizabeth Yu, Eiji Yoshihara, Sandra Jacinto, Yelizaveta Lukasheva, Annette Atkins and Ruth Yu of the Salk Institute; Shannon Reilly and Alan Saltiel of the University of Michigan; Olivia Osborn, Denise Lackey, Bernd Schnabl, David Brenner and Jerrold Olefsky of the University of California, San Diego; Alessia Perino and Kristina Schoonjans of the École Polytechnique Fédérale de Lausanne; Alexander Khvat of ChemDiv; and Sally Coulter and Christopher Liddle of the University of Sydney.
http://www.salk.edu/news