Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Instituto de Medicina Molecular, Cenix BioScience, and Alnylam Pharmaceuticals Discover New Pathway for Malaria Infection

12.09.2008
Cenix BioScience GmbH, a leading specialist in advanced RNA interference (RNAi)-based research services, Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and the Lisbon-based biomedical research centre Instituto de Medicina Molecular (IMM), today announced the publication of their collaborative study in Cell Host & Microbe, describing the discovery and in vivo validation of scavenger receptor BI (SR-BI), a major regulator of cholesterol uptake by the liver, as a critical host factor for malaria infection.

The new research findings are the first to describe a molecular link between cholesterol metabolism and malaria infection, and the new data could lead to new approaches for the treatment of malaria including use of RNAi therapeutics.

“Malaria represents a major global health concern accounting for approximately two million deaths per year. Nevertheless, the molecular mechanisms for the parasite’s pathophysiology have remained poorly understood,” said Maria Mota, Ph.D., Director of the Malaria research Unit at the IMM. “Our current studies advance the potential for new therapies as we have discovered an important molecular link between the earliest stages of infection and a critical host gene.”

The published report by Rodrigues, Hannus and Prudêncio et al. (Cell Host & Microbe 4, 271-282; 2008) describes the results of studies to investigate a decade-old hypothesis that lipoprotein clearance pathways in the human host may somehow impact the infection of liver cells by malaria-causing Plasmodium parasites. In the study, the liver-expressed gene, SR-BI, was identified as a critical host factor for the liver infection stage of malaria using a systematic RNAi screen of known lipoprotein pathway components in a cultured human cell-based infection assay.

These finding were then confirmed in animal models of malaria infection using small interfering RNAs (siRNAs), the molecules that mediate RNAi, specific for SR-BI silencing. SR-BI is well-known as the major liver receptor for high density lipoproteins (HDL), where it plays a key role in the transfer of cholesterol from the bloodstream to hepatocytes. In addition to studies using RNAi-mediated gene silencing, the pathophysiological relevance of SR-BI’s requirement for malaria infection was confirmed by a comprehensive series of experiments using synthetic small molecule inhibitor compounds, blocking monoclonal antibodies, SR-BI over-expression with transgenic mice, and SR-BI loss of function with knock-out mice. As such, this study establishes the first clear molecular link between malaria infection and cholesterol uptake pathways, thus describing a new therapeutic strategy in the fight against this devastating parasitic disease.

“All of these studies not only demonstrate the power of our RNAi-based discovery platform, but most importantly, they open brand new interventional routes for developing novel treatments for malaria and other major parasitic diseases now devastating some of the world’s most vulnerable populations,” said Dr. Christophe Echeverri, CEO/CSO of Cenix. “The various SR-BI-inhibitor molecules demonstrated in this study as having anti-malarial activity, including siRNAs, small synthetic molecules, and antibodies, all represent interesting candidates for the development of novel prophylactic options. Importantly, their equally novel host factor-based mechanism of action promises an inherently more powerful interventional strategy against the emergence of resistant strains of malarial parasites, as compared to existing parasite-targeted therapies.”

“We’re very pleased to participate in the research efforts initiated at the IMM with Cenix,” said Victor Kotelianski, Senior Vice-President and Distinguished Alnylam Fellow. “We feel particularly gratified that our core technology for systemic therapeutic gene silencing with RNAi therapeutics has played an important role in advancing the characterization of novel targets to confront this killer disease, and we look forward to further supporting ongoing efforts to tackle malaria and other major threats to global health.”

The current work results from an ongoing malaria research program started by the IMM group and their longstanding collaboration with Cenix, announced in 2005 to apply high-throughput RNAi technologies for discovery of host factor genes involved in malaria infection. This work was extended to include Alnylam’s technologies for in vivo delivery of siRNAs. Together, the collaborators have established a major new platform to drive the systematic, genomics-driven discovery and validation of novel human host genes offering clear therapeutic or prophylactic potential for halting malaria infection at its earliest liver stage, before onset of the disease’s symptomatic blood stage.

Driven by Dr. Mota’s ongoing malaria research and the efforts at Cenix and Alnylam, the partners are also seeking opportunities to further scale-up the use of this platform to extend the present screen over the rest of the human genome, and to broaden the reach of these capabilities beyond malaria, tackling other parasitic diseases of major relevance to global health, including so-called neglected diseases of the developing world.

Marta Agostinho | alfa
Further information:
http://www.fm.ul.pt

More articles from Interdisciplinary Research:

nachricht New approach: Researchers succeed in directly labelling and detecting an important RNA modification
30.04.2018 | Westfälische Wilhelms-Universität Münster

nachricht Start of work for the world's largest electric truck
20.04.2018 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Interdisciplinary Research >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

When corals eat plastics

24.05.2018 | Ecology, The Environment and Conservation

Surgery involving ultrasound energy found to treat high blood pressure

24.05.2018 | Medical Engineering

First chip-scale broadband optical system that can sense molecules in the mid-IR

24.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>