Kolkata, Sep 3 (IANS): With drug resistance threatening the battle against kala azar, which afflicts 350 million in 88 countries, a group of Indian scientists has taken a giant step to develop a potential therapy by using tiny molecules present in the body.
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.
"Kulingana na ripoti ya utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti.""" "Hata hivyo, asilimia 65 ya wagonjwa nchini India wameacha kujibu dawa ya ""sodium stibogluconate,"" ambayo ni dawa inayotumiwa kwa ugonjwa wa leishmaniasis au kala azar, anasema Neelam Singh, mwanasayansi mkuu wa Taasisi ya Kati ya Utafiti wa Dawa (CDRI) huko Lucknow." "Sodium stibogluconate ni salama, yenye matokeo na ya bei nafuu. "Kala Azar ni ugonjwa wa maskini na kwa hivyo dawa hiyo ilikuwa muhimu, lakini sasa vimelea vimekuwa na sugu kwa hilo. """ Dawa nyingine ambazo zina ufanisi kama vile amphotericin na miltefosine ni ghali na zenye sumu, "Neeloo Singh aliiambia IANS. Takwimu za awali za Wizara ya Afya ya Umoja wa Mataifa zinaonyesha kuwa ugonjwa wa Khala Azar umesababisha vifo vya watu 11 na kuambukiza watu 7,776 mwaka huu hadi Julai. Utafiti wa utafiti uliofanywa na watafiti wa Taasisi ya Kemia ya India (IICB) unaonyesha kuwa kuna uwezekano mkubwa wa kupunguza kiwango cha kolesteroli katika damu, na hivyo kupunguza idadi ya wadudu hao. Inahusisha kuelekeza baadhi ya molekuli ndogo ambazo ni bidhaa za moja kwa moja za jeni. "Wakati tulitoa RNA ndogo (micro Ribonucleic Acid - molekuli ndogo) kupita kiasi iliongeza cholesterol na wakati huo huo kusababisha uondoaji wa vimelea. """ "Hiyo ni moja ya sababu za kuonekana kwa dawa hii katika majaribio ya utafiti, ""alisema Suvendra Nath Bhattacharya, mkurugenzi wa Idara ya Molecular na Genetics ya Binadamu ya IICB, katika taarifa yake kwa IANS." MicroRNA (miRNA) ni sehemu muhimu ya mfumo wa metabolic, pamoja na metabolism ya cholesterol katika ini, na inajumuisha 22 vitengo vya molekuli za kikaboni zinazoitwa nucleotides. Katika mwili, mashine hizi ndogo-ndogo husimamia usemi wa chembe za urithi na kusaidia kudhibiti utengenezaji wa bidhaa za kazi kama vile protini. Kwa ajili ya majaribio yao, wanasayansi walitumia RNA ndogo maalum kwa ini ambayo inabadilisha kimetaboliki ya mafuta katika kiungo. Kwa mfano, Leishmaniasis, aina ya vimelea vinavyopiga ini na kuzidisha katika utumbo, huathiri kiwango cha miRNA kwa kuelekeza enzyme inayoitwa dicer, ambayo ni muhimu kwa uzalishaji wa micro-regulators. "Kama vimelea vinavyopunguza kiwango cha kolesteroli, hali hiyo inasaidia kwa vimelea kukua, ""alisema Bhattacharya, ambaye pia ni mwanasayansi wa IICB, ambaye amethibitisha kuwa kolesteroli ni moja ya modulators kuu ya mchakato huu wa maambukizi." Kwa kutumia uhusiano kati ya kolesteroli na microRNA, timu hiyo ilitumia microRNA nyingi zaidi, na hivyo kuongeza kiwango cha kolesteroli na hivyo kuzuia maambukizo. "Ni jambo la maana sana kwamba wanasayansi wapate njia mpya za tiba. "Watu walioathirika ni wasio na msaada kwa sababu ya upinzani wa dawa, ""alisisitiza Singh, ambaye pia ni mmoja wa wanachama wa mwanzilishi wa Leishmaniasis Research Society (India)." "Tiba ya WHO ya ""ugonjwa uliopuuzwa"" inaweka karibu watu milioni 165.4 katika hatari ya kuambukizwa na ugonjwa huo katika Bihar, Jharkhand, Uttar Pradesh na Bengal Magharibi."