September 21 : An international team of researchers has discovered several genetic secrets about Brugia malayi (B. malayi), one of the world’s most debilitating human parasites, which is responsible for the disfiguring disease elephantiasis.

Published in the journal Science, the study highlights dozens of potential new targets for drugs and vaccines to treat and prevent elephantiasis, besides providing new opportunities to understand the disease.

The female B. malayi worms can live up to eight years in the human body and cause elephantiasis. The longevity of B. Malayi complicates treatment because existing drugs target the larvae, and thus do not completely kill the worms.

Furthermore, the worm can cause a massive immune reaction when it dies besides releasing foreign molecules, say the study’s authors.

Dr. Elodie Ghedin, assistant professor of infectious diseases, University of Pittsburgh School of Medicine, believes that having a complete genetic blueprint of the organism will undoubtedly lead to the development of much better therapies.

“The genomic information gives us a better understanding of what genes are important for different processes in the parasite’s life cycle. So, it will now be possible to target these genes more specifically and interrupt its life cycle,” said Dr. Ghedin, who led the sequencing project while at The Institute for Genome Research, which is now part of the J. Craig Venter Institute, a not-for-profit research organization in Bethesda, Md.

As part of the study, published in the journal the 90 million base pair genome of B. malayi across the globe were analysed. The sequence analysis predicted approximately 14,500 to 17,800 protein coding regions (genes) in B. malayi genome, which was in agreement with previous estimates.

Upon comparing the analysis of B. malayi genome with that of another nematode called Caenorhabditis elegans, the researchers found that more than 20 per cent of the predicted proteins in B. malayi were specific to the parasite.

Dr. Ghedin suggests that the B. malayi-specific genes, almost 2,000 in all, constitute an “interesting list” of initial candidates for functional studies of the gene products.

Her team has also identified several metabolic pathways containing dozens of gene products that may be helpful for the discovery of more targeted and effective drug therapies. These include pathways involved in molting, nuclear receptor responses, collagen processing, neuronal signaling, protein phosphorylation (i.e., protein kinases) and host and endosymbiont metabolism.

“Insights into the gene activation pathways of B. malayi will undoubtedly speed the pace of discovery of new treatments. And any new interventions to reduce the burden of disfiguring elephantiasis around the world will indeed be welcome,” said Dr. Donald Burke, dean of the University of Pittsburgh Graduate School of Public Health.

A comparative analysis of the B. malayi genome with that of interleukins, chemokines and other immune signalling molecules from humans showed a number of candidates, which the researchers believe are responsible for allowing the nematode to evade immune detection.

The researchers say that these proteins may be immune modulators that promote the survival of the parasite or allow its development.

Dr. Alan L. Scott of the Bloomberg School of Public Health at Johns Hopkins University, a collaborator on the study, said that understanding how this particular parasite has adapted to humans might yield medical benefits far beyond treating elephantiasis.

“Parasitic worms are a lot like foreign tissue that has been transplanted into the human body. But unlike baboon hearts or pig kidneys, which the immune system quickly recognizes as foreign and rejects, worms can survive for years in the body. Discovering how they do so may someday benefit transplant surgery,” explained Dr. Scott. (ANI)