Indian Scientists Overcoming Drug Resistance in the Battle Against Kala Azar

by Kathy Jones on Sep 5 2013 8:09 PM

 Indian Scientists Overcoming Drug Resistance in the Battle Against Kala Azar
A group of Indian scientists has taken a giant step to develop a potential therapy for kala azar by using tiny molecules present in the body. It is estimated that kala azar affects 350 million in 88 countries and drug resistance is a major challenge in treating it.
Around 65 percent patients in India have stopped responding to sodium stibogluconate - the drug of choice for the life-threatening visceral leishmaniasis or kala azar, says Neeloo Singh, senior principal scientist, Central Drug Research Institute (CDRI), Lucknow.

"Sodium stibogluconate is safe, effective and inexpensive. Kala azar is a poor man's disease and therefore the drug was essential, but now the parasite has become resistant to it. Other drugs which are effective like amphotericin and miltefosine are expensive and toxic," Neeloo Singh told IANS.

Provisional figures by the union health ministry show that kala azar claimed 11 lives and afflicted 7,776 people this year till July.

Upping the ante against drug resistance, researchers at the Indian Institute of Chemical Biology (IICB) here have pioneered a new strategy to increase the cholesterol level in blood, that in turn significantly slashes the parasite's numbers. It involves channelising some small molecules that are the direct products of genes.

"When we administered the micro RNA (micro Ribonucleic Acid - the small molecules) in excess it increased the cholesterol and at the same time induced clearance of the parasite. It emerged as the potential molecule in combination with other drugs," Suvendra Nath Bhattacharyya of the Molecular and Human Genetics Division of the IICB here, told IANS.

These micro RNAs (or miRNA) are important for regulating key metabolic processes, including cholesterol metabolism in the liver, and are composed of 22 units of organic molecules called nucleotides.

In the body, these mini machines regulate expression of genes and help control production of functional products like proteins.

For their experiments, the scientists used the micro RNA specific to the liver that modulates fat metabolism in the organ.

What was of interest to scientists was that the Leishmania parasite (that infects the liver and multiplies in the spleen) brings down the miRNA levels by "targeting an enzyme called dicer that is responsible for the production of these micro regulators".

When the parasite brings down the microRNA, this in turn lowers cholesterol - a condition that is favourable for the parasite to thrive

"It will reduce the microRNA and it will reduce the cholesterol in the blood and this is important for the parasite because previously it has been shown by IICB scientists that cholesterol is one of the main modulators of this infection process," Bhattacharyya said.

Using the cholesterol-microRNA correlation to their advantage, the team administered microRNAs in excess that resulted in increased cholesterol and the subsequent resistance to the infection.

"It is of paramount importance that scientists find out new therapy methods. The afflicted are helpless due to drug resistance," stressed Singh, who also doubles as one of the founding members of the Leishmaniasis Research Society (India).

Termed by the World Health Organisation as a neglected disease, the disease puts an estimated 165.4 million people at risk in Bihar, Jharkhand, Uttar Pradesh and West Bengal.