Using Disease Proteomics to Control Malaria

Every year, malaria affects 300-500 million people worldwide and causes over one million deaths, many of which are children.¹ Despite periodic successes with drug treatment at the end of the twentieth century, the more recent use of disease proteomics has been essential to better understanding the biochemical changes associated with malaria, thus providing researchers with better paths toward combating the disease.

Drug resistance poses a significant problem across a range of diseases, making it impossible to have one-size-fits-all treatment plans. In many cases, the cause of resistance remains unknown. For example, chloroquine was once one of the most reliable drugs used to treat malaria; however, in 1990, its use was withdrawn because it had become almost ineffective in many parts of the world. The parasite that causes malaria developed resistance to the treatment. However, just nine years after its withdrawal, Chloroquine became effective again.

Disease proteomics have been largely responsible for identifying potential new therapeutic targets for Plasmodium falciparum, the malaria-causing parasite, and improving our understanding of the disease.^2,3 Antimalarial drugs rely on being able to target a particular pathway, and similarly, vaccines confer immunity by causing the body to develop a long-term memory of the organism’s surface proteins. However, differential protein expression in Plasmodium falciparum makes it difficult to create vaccines and antimalarial drugs because of the changing metabolic pathways and surface coatings over the organism’s life cycle.⁴

Gitau et al.⁵ employed a global disease proteomics strategy to identify proteins, which are differentially expressed in mouse models of malaria. They identified a number of expressed proteins, including proteins affected during the acute phase of infection. This study validates the use of proteomics to characterize proteins that are differentially expressed.

Gitau’s results also suggest that apoptosis and inflammation may play a major role in the progression of malarial disease. A proteomics analysis of the markers of activated macrophages associated with inflammation could help in understanding their role in controlling malaria and confirm thier relevance in developing immunity to infection.

Disease proteomics has had a major impact on drug development, as identification of differentially expressed proteins adds to the list of potential antimalarial drug targets. Ultimately, these can be tested against commercially available libraries of chemical compounds to find lead compounds for further optimization. Additionally, studies such as Gitau’s offer a new opportunity to understand disease by looking at proteins associated with the changes that take place in the presence of disease. Hopefully, the knowledge gained through the study of proteins will result in better treatments to control malaria and its global spread in the near future.

References

1. WHO Division of Child Health and Development (1997) ‘WHO: Integrated management of childhood illness: conclusions’, Bull World Health Organ, 75 (Suppl 1), (pp. 119-128)

2. Mwai, L., et al. (2009) ‘Chloroquine resistance before and after its withdrawal in Kenya‘, Malaria Journal, 8, (p. 106).

3. Kavallaris, M. and Marshall, G.M. (2005) ‘Proteomics and disease: opportunities and challenges‘, Medical Journal of Australia, 182 (11), (pp. 575-579)

4. Florens, L., et al. (2002) ‘A proteomic view of the Plasmodiumfalciparumlife cycle‘, Nature, 419 (6906), (pp. 520-526)

5. Gitau, E.N., et al. (2011) ‘Global proteomic analysis of plasma from mice infected with Plasmodium berghei ANKA using two dimensional gel electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry‘, Malaria Journal, 10, (p. 205)

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