Developing the next generation of anti-mitotic drugs

Developing the next generation of anti-mitotic drugs as new anti-parasitic drugs by studying the role of microtubules in apicomplexan parasite biology (P. falciparum and B. bovis)

Imagine a world where the only drugs available for your diseases are now defunct because they no more work against those diseases! Sounds apocalyptic, doesn't it?

In the realm of parasite biology, IITB-Monash Research Academy research scholar Rimi Chakrabarti hopes to avoid exactly such a situation by facilitating the development of anti-mitotics (most commonly used for cancer) as novel, next-generation anti-parasitic drugs. Her research aims to do this by studying the effects of anti-mitotics on the micro-tubular structure of apicomplexan parasites, paritculary, Plasmodium falciparum (causes malaria in humans) and Babesia bovis (infects cattle and occasionally, humans).

Microtubules are fibrous, empty rod-like structures that function primarily in supporting and shaping a cell. Research in P. falciparum has demonstrated that some of the well known cancer drugs have anti-parasitic effects, probably because of their anti-microtubule action. However, unlike mammalian cells, the cells of apicomplexan parasites inside host RBCs, are only 6 microns across, making it difficult to study their microtubules accurately. Additionally, there are technical issues in the area of in vitro binding studies of purified parasite tubulin (microtubule protein) with drugs, since large scale production of this microtubule protein is still not feasible. This poses a problem because data from these studies would have been very useful to determine the role played by microtubules in parasite biology.

Rimi Chakrabarti believes that rewards and benefits of this research are manifold. Firstly, understanding the functional role of microtubules will paint a clearer picture of the anti-proliferative ability of anti-tubulin compounds in parasites. Second, some of these compounds that have already been tested and validated as anti-tubulin have combated parasitic tubulin better than mammalian. This presents an unparalleled chance to use a validated cancer drug as an anti-malarial or anti-babesial at a much lower dosage without the concern of its being poisonous to the host. And finally, since drug resistance is fast becoming the nemesis of modern medical science, alternative forms of drugs are the need of the hour. For example, different strains of P. falciparum are now reported to be resistant to most available drugs, except quinine. A deeper understanding of the functional role of microtubules will lead to faster development of next generation drugs, such as the alternative use of anti-mitotics seen so far.

Malaria and bovine babesiosis have been cause for grave concern across the world because of their high mortality rates, reiterating the need for studies such as this one undertaken by Rimi Chakrabarti:

The development of anti-malarial drugs has been on the backburner since about 400 years, with no effective vaccine yet and only 12 currently available drugs including quinine which has led and ruled the roost from 1623, as opposed to hundreds of anti-bacterials developed each year.

Artemisinin, the 'latest' anti-malarial drug was added to the existing lot nearly 40 years ago in 1971. Often called a "poor man's disease ", thriving mostly in developing countries and the tropics, malaria seems to have been relegated to the abyss in drug development efforts. A mosquito bite, seemingly insignificant in the larger scheme of things, becomes the harbinger of death for 1 million people each year; a majority is children below the age of 5.

Bovine babesiosis:
With its only functional drug, Imidocarb, along with a marginally effective babesia vaccine, Bovine babesiosis joins malaria on the backburner of drug development efforts. The cattle industry could be characterized by a booming economy if new babesia drugs are developed, thereby shrinking costs attributed to mortality, slow growth, and lower milk/meat production.

This research by Rimi Chakrabarti will not only prove to be a vibrant new breakthrough in the field of therapeutics and pharmacology, but also demonstrates that the only way forward is the assimilating of progressive new media in the realm of parasite biology if the future is to be robust, effectual and sustained.

Rimi Chakrabarti says about her work, "Any new drug developed against malaria/babesiosis would not only be a valuable addition to an already depleting arsenal of first line of therapeutics, it would also buy us some time to develop effective vaccines against these diseases." She also attributes her sustained interest in the subject to the pro-growth and learning environment at IITB-Monash Research Academy, saying "Working on this project has been rewarding, particularly because of the opportunity to be trained in some of the very advanced techniques in the field of parasitology."

Established in 2008, IITB-Monash Research Academy is an important collaboration between Australia and India. It offers graduate research scholars the opportunity to study for a dually-badged PhD from both IIT Bombay in India and Monash University in Australia, spending time in both countries over the course of their research.

Research scholar: Rimi Chakrabarti, IITB-Monash Research Academy

Project title: Functional properties and arrangement of apicomplexan tubulin and the action of anti-tubulin compounds as chemotherapeutic agents.

Supervisors: Ross Leon Coppel, Brian Mark Cooke, Swati Patankar

Contact details:rimi.chakrabarti@monash.edu , rimichakrabarti@iitb.ac.in

For more information and details on this technology, email research@iitbmonash.org The above story was written by Ms. Sheba Sanjay based on inputs from the research student and IITB-Monash Research Academy.