Prizes and Parasites

One subject attracting a great deal of attention this week at the IGWG meeting in Geneva is that of prizes as an alternative incentive approach for neglected disease R&D, with multiple different examples of prize proposals on the table. In following the negotiations, it has been have noted that there have been questions about the relative difficulty of various research programs discussed in the prize proposals that have been put forward. Specifically, the proposal on Chagas disease has been questioned on the grounds that it is too difficult of a problem, citing the lack of success to date. While it is indeed true that we currently lack effective treatments and vaccines for Chagas - and, in fact, for the majority of parasitic diseases - there is no a reason to think that these diseases are insoluble. We are aggressively pursuing treatment for extremely complex diseases such as Alzheimer’s, and, despite the enormous amounts of money being thrown at this disease, many doubt that a cure or even an effective treatment will ever be found. Parasitic diseases, while not simple to address, should in no way be thought of in the same category of complexity as diseases such as Alzheimer’s - a disease to which we devote many times the amount of resources. In fact, given the relatively tiny amount of funding put towards parasitic diseases thus far, it is somewhat amazing that we have made as much progress as we have.

Lack of progress?
There are, undoubtedly, a number of hurdles to overcome in the development of medicines and vaccines for parasitic diseases. However given the funding situation to date, there has been no reason to expect rapid progress, and in many ways the field of parasitology is still in its infancy in comparison to other, better funded, areas. Part of the difficulty in addressing parasitic disease is that parasites have a very complex relationship with the human immune response. With the enormous increase in our understanding of immunology that has occurred over the last decade, we now have a much better foundation of knowledge to understand many of the intricacies involved in manipulating the host response to fight parasitic infections. Furthermore, what we do know thus far about parasitic diseases indicates that the hurdles to the development of effective medicines and vaccines are by no means insurmountable.

Progress on Vaccines
With regard to vaccines, the large majority of studied cases demonstrate that parasitic infection has the ability to confer protective immunity (1) - thereby meeting a crucial criteria for the ability to develop an effective vaccine. Specifically regarding Chagas, several labs have demonstrated complete protection of vaccinated mice against challenge with a lethal dose of T. cruzi (the parasite that causes Chagas) (2, 3, 4). Already, multiple antigens and vaccine types have been show to confer complete protective immunity in mice, providing multiple possible options to explore for a potential vaccine in humans. With further funding on basic research for Chagas disease, there will undoubtedly be more protective antigens uncovered.

Progress on Anti-parasitic drugs
With regard to the development of anti-parasitic drugs, there is the potential for a single drug or drug class to be effective against multiple parasitic infections, just as the penicillin family of antibiotics are effective for diseases ranging from strep throat to syphilis. By taking advantage of how parasites are similar to each other but different from humans, there is the potential to develop targeted treatments with good side effect profiles that are effective against multiple parasites. The most well-researched such drug target to date is an enzyme called PNP which is involved in the only possible pathway for most parasites to obtain the building blocks to replicate their genetic material (5). Again, with more funding on basic science research into parasitology, several more potential drug targets are likely to be uncovered.

Potential for Innovative Incentive Approaches for R&D for Parasitic Disease
Because parasitic diseases almost exclusively effect developing countries, it is not surprising that there has been such a small amount of funding for R&D related to parasitic disease. In terms of setting up effective incentive structures for the medicines and vaccines for parasitic diseases, one possibility to keep in mind is a dual-market licensing approach whereby a drug is developed for use in the developing world while simultaneously being developed to meet a different need in the developed world. Anti-parasitic drugs account for over 40% of veterinary medicines used today (6, 7). Parasitic disease in animals result in significant economic loss in the livestock and associated industries, and there is a need for more effective treatments (8, 9). Thus a dual-market licensing approach might be particularly useful to incentivize research into medications and vaccines for parasitic disease. As an example of successful uses of this strategy, in 2003 Yale University pursued a dual-market approach by licensing a series of azole compounds simultaneously for parasitic disease in the developing world and fungal infections in the developed world. There has been a similar proposal discussed, also at Yale, to license a hookworm vaccine for pediatric use in the developing world and for use in the livestock industry in the developed world.

Prizes and Chagas
Chagas is a disease that almost exclusive effects poor populations in the developing world. Especially given that there is no travelers market, it is not particularly surprising that there has been such little funding directed toward this disease. This lack of adequate market incentives is one of the reasons that Chagas would in fact make an excellent candidate for a prize proposal. In addition, research on Chagas could help further our understanding of parasites in general, thereby advancing work on treatment for other parasitic diseases. Finally, Chagas causes significant morbidity and mortality and current treatment options are completely insufficient to alleviate the suffering caused by this disease; we have an obligation to find a way to develop these much needed treatments.

Sara Crager
MD/PhD Candidate ‘12, Yale University
Universities Allied for Essential Medicine

References
1. Infection, Genetics and Evolution 7 (2007) 664–673
2. Vaccine. 2008 May 2;26(19):2322-34.
3. Vaccine. 2008;26(16):1999-2009.
4. Infect Immun. 2008 Jan;76(1):324-33.
5. Curr Drug Targets. 2007 Mar;8(3):413-22
6. Exp. Parasitol. 112, 274–279
7. Parasite Immunol. 2006 28, 61–67.
8. Vercruysse, J., et al. Trends Parasitol. 20, 488–492.
9. Parasitology Today Volume 2000 16, Issue 12 (1) Pages 504-506