Australian army faces legal action over mefloquine
The Australian army and Roche Products Australia face a class action after allegations that army personnel had serious side effects after being prescribed mefloquine hydrochloride (Lariam) as part of a research trial for a new anti-malarial drug.
Since 1998, the Army Malaria Institute, a research organisation of the Australian Army, has been working with the Royal Thai Army and the US Army to trial an experimental drug, tafenoquine. In 1999, the institute, in collaboration with SmithKline Beecham, started a trial reportedly of about 600 Australian troops serving as part of the United Nations peacekeeping forces in Bougainville and later in East Timor. Mefloquine was used as the comparator.
Simon Harrison, a lawyer with the Brisbane based legal firm Quinn and Scattini, plans to file legal complaints in the next few weeks on behalf of numerous service personnel, complaining about serious side effects from the drug. Mr Harrison says that army personnel were not adequately informed about the potential side effects. The legal action will allege that the plaintiffs had depression, kidney damage, paranoia, and suicidal thoughts after taking the drug.
The Australian drug regulator, the Therapeutic Goods Administration, requires Roche Australia to include a four page product information sheet with prescriptions of the drug. The current information sheet, prepared in 1998, warns consumers who experience "depression, restlessness, confusion, feeling anxious or nervous" to inform their doctor immediately. "Other side effects not listed above may also occur in some patients," it states.
GenVec Expands Malaria Vaccine Program Under U.S. Naval Medical Research Center Contract
GAITHERSBURG, Md., Jan. 20 /PRNewswire-FirstCall/ -- GenVec, Inc. (Nasdaq: GNVC) has signed a $1.6 million contract with the Department of Defense to manufacture an adenovector based malaria vaccine candidate for the U.S. Naval Medical Research Center (NMRC) using GenVec's proprietary adenovector technology and 293-ORF6 cell line based manufacturing process. The vaccine is based on two antigens and is designed to attack multiple stages in the lifecycle of the P. falciparum malaria parasite. The NMRC will use some of the materials manufactured under this contract to complete preclinical testing in preparation for a planned clinical trial, which will be executed by the NMRC.
"We are pleased to see another vaccine candidate using GenVec's technology move forward into the clinic," said Joseph T. Bruder, Ph.D., GenVec's director of vector and vaccine programs. "Through our excellent collaborative relationship with the NMRC, we hope to make significant progress against malaria, a disease that causes over one million deaths each year, mostly among children, and threatens the health of our troops and travelers abroad." GenVec's vaccine program applies the Company's unique delivery technology and 293-ORF6 cell line to develop vaccines against a variety of diseases, including malaria, HIV, dengue virus and SARS. The Vaccine Research Center of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, is currently testing a vaccine developed in collaboration with GenVec against the virus that causes AIDS in a Phase 1 dose-escalation study. Enrollment in this first HIV clinical trial has been completed.
Support for the manufacturing and clinical development of this adenovector based malaria vaccine candidate is provided by the U.S. Agency for International Development Malaria Vaccine Development Program, the U.S. Department of Defense Military Infectious Disease Research Program, and the Office of the Congressionally Directed Medical Research Program.
GenVec is a publicly held biopharmaceutical company focused on the development and commercialization of novel therapies that improve patient care in the areas of cancer and cardiac disease, and to prevent vision loss. GenVec is also developing vaccines. The vaccines against malaria and HIV discussed in this release have not been approved by the Food and Drug Administration. GenVec is not responsible for the design or conduct of these clinical trials. Additional information on GenVec is available at http://www.genvec.com and in the Company's various filings with the Securities and Exchange Commission.
Statements herein relating to future financial or business performance, conditions or strategies and other financial and business matters, including expectations regarding future programs and studies, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act. GenVec cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include risks relating to the early stage of GenVec's product candidates under development; uncertainties relating to clinical trials; the timing and content of future U.S. Food and Drug Administration regulatory actions with respect to GenVec, its product candidates, or collaborators, risks relating to the commercialization, if any, of GenVec's proposed product candidates (such as marketing, regulatory, patent, product liability, supply, competition and other risks); dependence on the efforts of third parties; dependence on intellectual property; and risks that we may lack the financial resources and access to capital to fund our operations. Further information on the factors
and risks that could affect GenVec's business, financial conditions and results of operations, are contained in GenVec's filings with the U.S. Securities and Exchange Commission (SEC), which are available at http://www.sec.gov. These forward-looking statements speak only as of the date of this press release, and GenVec assumes no duty to update forward- looking statements.
SOURCE GenVec, Inc.
Web Site: http://www.genvec.com
Scientists Reveal Molecular Secrets Of The Malaria Parasite 1-20-05 http://www.sciencedaily.com/releases/2005/01/050110123355.htm In an innovative project with implications for malaria vaccine development, scientists have used genomics, proteomics and gene expression studies to trace how malaria parasites evolve on a molecular level as they move between their hosts and insect vectors.
That unprecedented focus on the parasites’ complex life cycle is helping researchers understand when different genes switch on and off as the pathogens metamorphose through seven different life stages. In turn, that molecular-level data will benefit biomedical scientists who are identifying new targets for vaccines that would impede the parasite during stages when it is particularly vulnerable to intervention.
“We hope this project will help vaccine researchers find the best targets against malaria,” says scientist Neil Hall, the first author of the paper that appears in the January 7th issue of Science. “The study’s findings will help scientists identify parasite genes that are interacting with the host as well as new gene targets for vaccines that aim to prevent parasite transmission in the mosquito.”
The study highlights the genes in four malarial species that evolve rapidly because of “selective pressures” in the stages of their life cycles in their mosquito vectors and in their mammalian hosts. Malaria parasites undergo three stages in their mosquito vectors, three stages in their vertebrate hosts and a sexual development stage during which the parasite is transmitted between vector and host.
The Science paper represents the culmination of four years of cooperative work by scientists at several research institutes, including: the Wellcome Trust Sanger Institute in the U.K., where the sequencing and genome annotation was performed on two species of rodent malaria (Plasmodium chabaudi and P. berghei); the University of Leiden in the Netherlands and Imperial College in England, where scientists carried out gene expression studies; and The Institute for Genomic Research (TIGR), in Maryland, where scientists did a comparative analysis of the two draft genomes with those of the first rodent malaria parasite to be sequenced, Plasmodium yoelii.
The first author of the paper is Hall, a TIGR Assistant Investigator who did most of his work on this project while in his previous position as a bioinformatics scientist at Sanger. He was also the first author of the 2002 study – led by scientists at TIGR, Sanger, and Stanford University – that presented the complete genome of Plasmodium falciparum, the deadliest human malarial parasite.
Hall says the Science paper is important because:
* The study takes an “evolutionary approach” to exploring how the Plasmodium genome has evolved. By comparing four sequenced genomes (the human malaria P. falciparum and the rodent malarias P. yoelii, P. chabaudi and P. berghei), the scientists found that the major differences between the malarial species are found in the virulence factors (which are at the chromosome ends) while the “housekeeping” genes are almost totally unchanged.
* Researchers showed that the parasite genes evolve most rapidly when they are expressed in the mammal hosts (human/mouse). That may represent a mechanism by the parasites to repulse the attack of the host’s immune system.
* For the first time, scientists were able to study the protein expression of the parasite in the mosquito vector. Researchers hope this will shed light on how the mosquito and parasite interact, and perhaps will lead to new ways of controlling the parasite in the vector.
* Hall and Leiden scientists identified evidence of an unusual method of gene regulation (called post transcriptional regulation) at the transition between the vertebrate host and the mosquito. That motif regulates proteins that are switched on as the parasite enters the mosquito.
Hall’s group identified the gene regulation by comparing the genes expressed in the sexual stage transcriptome with the proteomes of both the sexual stage and a developmental stage in the mosquito. Several genes were identified for which transcripts were detected in the sexual stage but with protein products specific to the mosquito stage, indicating delayed translation of transcripts from these genes.
Hall says that gene-regulation motif “is particularly interesting because these proteins, expressed early in the mosquito, are the target of transmission-blocking vaccines" – that is, vaccines which raise antibodies that attack the parasite in the vector. (Such antibodies are in the “blood meal” and still work for an hour or so after the mosquito bites).
Another TIGR scientist who played an important role in the project is Associate Investigator Jane Carlton, who had led the sequencing of P. yoelii at TIGR and who has worked on Plasmodium for most of her research career. While at the University of Florida, Carlton had led the first large-scale gene identification project in P. berghi – including information that was used by Leiden University researchers in their investigation of genes that are turned on during the parasite’s reproduction stage.
At TIGR, Carlton constructed a composite of all three rodent genome sequences (P. yoelii, P. berghei, P. chabaudi) by aligning them against the P. falciparum genome to create a whole-genome synteny map of the four species. TIGR scientist Shelby Bidwell helped in the generation of the synteny map. In collaboration with Leiden University researchers, they were then able to generate maps that compare the degrees of similarity among genes on P. falciparum chromosomes and its rodent-malaria counterparts.
“The paper is significant on many levels, including the integration of draft genome sequence data with microarray and protein expression data,” says Carlton. “This project also shows the power of collaboration between international institutes with different areas of expertise. It was remarkably productive collaboration.”
The Plasmodium study was sponsored by The Wellcome Trust, the European Union’s research directorate, and the U.S. National Institutes of Health.
The Institute for Genomic Research (TIGR) is a not-for-profit research institute based in Rockville, Maryland. TIGR, which sequenced the first complete genome of a free-living organism in 1995, has been at the forefront of the genomic revolution since the institute was founded in 1992. TIGR conducts research involving the structural, functional, and comparative analysis of genomes and gene products in viruses, bacteria, archaea, and eukaryotes.
Turmeric can combat malaria, cancer virus and HIV
T. V. Padma
11 March 2005
[NEW DELHI] Indian researchers are saying that turmeric, a yellow spice used in many national dishes, has shown potential as a weapon against malaria as well as promising effects against HIV and the virus that triggers cervical cancer. The latest findings are of significance to developing countries where malaria and HIV are serious public health concerns, and which bear 80 per cent of the global burden of cervical cancer. India alone has one-third of the world's cervical cancer cases.
Earlier studies had confirmed the anti-microbial, anti-tumour and anti-inflammatory properties of turmeric's main component, curcumin. Scientists at the Indian Institute of Science (IISc) in Bangalore and the University of Michigan Medical School, United States, showed that curcumin inhibits drug-resistant forms of Plasmodium falciparum, the parasite that causes cerebral malaria. When they fed curcumin to mice infected with Plasmodium bergheii, a related parasite that causes rodent malaria, the number of parasites in the mice's blood fell by 80 to 90 per cent.
In tests, curcumin completely protected up to 29 per cent of infected mice, say the scientists. "Curcumin may offer a novel treatment for malarial infection," says Govindrajan Padmanabhan, scientist emeritus at IISc and one of the authors of the research, which was published in Biochemical and Biophysical Research Communications in January. In a separate study, Bhupesh Prusty and Bhudev Das of the Institute of Cytology and Preventive Oncology in New Delhi reported that curcumin could help prevent cervical cancer, which is associated with the human papilloma virus (HPV) in 90 per cent of the cases.
The virus has two key genes - E6 and E7 - which bind to a protein in normal human cells to make them (the cells) cancerous. Curcumin binds with the same human protein, preventing the virus from doing so, say the researchers in the January 2005 issue of International Journal of Cancer. In laboratory studies, two hours after the scientists introduced curcumin to infected cells, the viral genes began to unbind from the human protein. Das told SciDev.Net that his institute was planning to start human trials in two or three months. A capsule containing curcumin will be inserted into the vagina of women infected with HPV daily for three to four weeks.
The capsule dissolves slowly, releasing the curcumin powder, which will eventually be expelled in the urine. In a further demonstration of turmeric's potential to help tackle killer diseases, when scientists at the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore 'fed' curcumin to HIV-infected cells in the laboratory, the virus stopped replicating. They say curcumin could be used to help formulate a combination of drugs to treat HIV infection. Tapas Kundu, associate professor at the centre, told SciDev.Net that curcumin stops an enzyme called p300 from performing its normal role of controlling the activity of human genes. Because HIV integrates itself into human genetic material, when p300 stops working, the virus can no longer multiply.
Kundu believes the same mechanism could explain curcumin's other anti-bacterial and anti-viral properties. The p300 enzyme belongs to a class called histone acetylase transferase (HAT) enzymes, which scientists hope could lead them to treatments for a variety of cancers, asthma and neurological disorders. The findings were reported in the December 2004 issue of Journal of Biological Chemistry.
Biochemical and Biophysical Research Communications 326, 472 (2005)
International Journal of Cancer 113, 951 (2005)
Journal of Biological Chemistry 279, 51163 (2004)
On March 5, 2003, the Doctor Yourself Newsletter (
http://www.doctoryourself.com/news/v3n8.txt ) suggested a novel approach for treating malaria, a disease that kills over two million people annually,mostly children: have all malaria patients take megadoses of vitamin C. I am very pleased to report that recent research has now validated this hypothesis.
"Falciparum malaria infection is associated with significant destruction of erythrocytes. This leads to the release of toxic metabolic products, including oxidant compounds. We measured the serum concentration of the antioxidant, ascorbic acid, in 129 patients presenting with acute falciparum
malaria infection and in 65 healthy individuals. . . (A)scorbic acid plays a significant role in the pathogenesis of acute falciparum malaria in adults. Infected children also need to be given supplemental doses of ascorbate in view of the weakness of their immune system." (Hassan GI, Gregory U, Maryam H. Serum ascorbic acid concentration in patients with acute Falciparum
malaria infection: possible significance. Braz J Infect Dis. 2004 Oct;8(5):378-381. Epub 2005 Mar 17. )
Though not affiliated with the above authors, we have actually been field-testing this idea for over ten years. In the early 1990's, I presented the megadose-vitamin-C concept to some of the missionary Sisters of St. Joseph based in Rochester, NY. The result was published in the Jan. 5, 2003 DY News http://www.doctoryourself.com/news/v3n4.txt :
"Vitamin C is now part of the daily lives of the Myky tribe in Brazil's Goias rainforests, thanks to the efforts of Sister Suzie Wills, SSJ and a number of other Sisters of St. Joseph. Suzie has been very effective in getting native people eating not only citrus fruits and berries, but also taking C powder and tablets on a regular basis. She reports healthier children and babies, and that infant mortality has dramatically decreased. Sister Suzie is now at Olinda, near Recife, Brazil, but is soon expected to be headed to back to Goiania."
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