Infectious disease

Plasmodium falciparum phospholipase C hydrolysing sphingomyelin and lysocholinephospholipids is a possible target for malaria chemotherapy Hanada, K. et al. J. Exp. Med. 195, 23–34 (2002)

The emergence of resistance in Plasmodium falciparum to drugs such as chloroquine highlights the need to develop new approaches to treating malaria. During the development of malaria parasites within erythrocytes, lipid metabolism rises dramatically, providing a possible therapeutic target. Hanada et al. have identified, cloned and characterized the parasite sphingomyelinase (SMase), an important enzyme in lipid metabolism. An inhibitor of SMase caused severe impairment of intra-erythrocytic parasite development.

Pharmacogenetics

Population distribution of human flavin-containing monooxygenase form 3: gene polymorphisms Cashman, J., Zhang, J., Leushner, J. & Braun, A. Drug Metab. Dispos. 29, 1629–1637 (2001)

Flavin-containing monooxygenase 3 (FMO3) is involved in the biotransformation of many drugs and chemicals. Cashman et al. report a statistically significant heterogeneity among ethnic subdivisions at three variable DNA sites in the FMO3 gene, which accounts for much of its variability of action. This indicates that individuals could be genetically screened to determine the FMO alleles that they express, in order to optimize the therapeutic dosages of drugs that are metabolized by FMOs.

Neurodegenerative disease

Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease Pavan, K. et al. Science 2001 Dec 20; [epub ahead of print]

Overexpression of α-synuclein, a protein that has been implicated in the onset of Parkinson's disease, in Drosophila melanogaster causes dopamine neuron loss, and thus provides a model of the human disease. Pavan et al. show that directed expression of the molecular chaperone HSP70 can prevent α-synuclein-induced neuron loss in Drosophila, and that neurotoxicity is accelerated by the loss of endogeneous chaperone activity. So, chaperone activation might be an effective therapeutic approach in humans.

Rational drug design

Protection against anthrax: identification of a site for rational drug design Glick, M., Grant, G. H. & Richards, W. G. Nature Biotechnol. (in the press)

Many will be familiar with the project started by Graham Richards' group, which uses 'spare' time on computers spread worldwide to screen virtual libraries for potential anti-cancer drugs. An analogous project screening for molecules that could bind to a ligand-binding site identified on a component of anthrax toxin and thus inhibit assembly of the toxin complex is now being initiated.