New hope for leishmaniasis
doi:10.1038/nindia.2008.105 Published online 22 January 2008
Conventional treatment for leishmaniasis or kala-azar, as of now, is chemotherapy with a host of drugs that could cause toxicity, are unaffordable or induce drug resistance. Vaccines for the disease have been tested unsuccessfully thus far.
Three different groups of researchers have now given hope for alternate routes to combat the causative parasite Leishmania.
The first study1 by scientists at the Central Drug Research Institute proposes ethanolic extract of the medicinal plant Tinospora sinensis Linn as a probable drug candidate for visceral leishmaniasis. The team tested the extract in infected hamsters to conclude that it may provide new lead molecules for the development of alternative drugs against the fatal disease.
The second promising lead2 came from researchers at the Indian Institute of Chemical Biology (IICB) who used human placenta extract as intramuscular injections in mice and subsequently in five human subjects to find that it improved the treatment of antimony-resistant cases of visceral leishmaniasis.
Based on the results of this pilot study for a phase one clinical trial, the researchers will further evaluate the efficacy of this therapy.
In the third study3 that could find an application in development of peptidomimetics (peptide inhibitors), another group of researchers at IICB worked on Topoisomerase IB, an enzyme important for the vital cellular processes of Leishmania.
The team gradually deleted head and tail sequences of the two subunits of the enzyme and identified the minimal functionally interacting fragments. These fragments generated the interacting regions from which specific interacting amino acids were delineated. “The fragments could complement the respective antisense knocked out wild type subunits inside the parasites,” says one of the researchers Somdeb Bose Dasgupta.
The same group had recently identified4 a protein with a role in drug resistance in the cell membrane of Leishmania.
More than 165 million people, mostly rural poor, are estimated to be at risk of kala-azar in India, the worst being the Bihar-Jharkhand-Uttar Pradesh-West Bengal belt.
- Singh, N. et al. Evaluation of antileishmanial potential of Tinospora sinensis against experimental visceral leishmaniasis. Parasitol. Res. doi: 10.1007/s00436-007-0822-2 (2007)
- Chakraborty, D. et al. Human placental extract offers protection against experimental visceral leishmaniasis: a pilot study for a phase-I clinical trial. Ann. Trop. Med. Parasit. 102, 21-38 (2008) | Article | PubMed |
- Bose Dasgupta, S. et al. Amino acids 39–456 of the large subunit and 210–262 of the small subunit constitute the minimal functionally interacting fragments of the unusual heterodimeric topoisomerase IB of Leishmania. Biochem. J. 409, 481-489 (2008) | Article | PubMed |
- Bose Dasgupta, S. et al. A novel ATP-binding cassette transporter, ABCG6 is involved in chemoresistance of Leishmania. Mol. Biochem. Parasit. doi: 10.1016/j.molbiopara.2007.12.007 (2007)