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Discovery of an HIV inhibitor in human blood points to new drug class

A new study has pinpointed a natural ingredient of human blood that effectively blocks HIV-1, the virus predominantly responsible for human AIDS, from infecting immune cells and multiplying. The virus blocker might play a role in the progression of HIV to full-blown AIDS and -- because it works in a different way than existing antiretroviral inhibitors -- could lead to the development of another class of drugs in the fight against the pandemic disease.

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Keywords: discovery, hiv, inhibitor, human, blood, points, drug, class, point

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1. Advance in understanding of blood pressure gene could lead to new treatments
   02-04-2007 · EurekAlert!
   Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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2. Effectiveness of first renin inhibitor drug for treating hypertension is limited
   05-09-2007 · EurekAlert!
   Hypertension is a serious condition affecting millions. There are seven classes of drugs used to reduce blood pressure. Aliskiren is the first of a new class of antihypertensive drugs that works by inhibiting renin. A review of six large clinical trials of aliskiren is being published in the May issue of the American Journal of Hypertension. The authors report that, because of reactive renin secretion, this drug has not been any more effective than those already widely available.
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3. Discovery in plant virus may help prevent HIV and similar viruses
   07-31-2007 · EurekAlert!
   In a study that could lead to new ways to prevent infection by human immunodeficiency virus and similar organisms, Purdue University researchers have been able to genetically modify a plant to halt reproduction of a related virus.
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4. Research finds that Earth's climate is approaching 'dangerous' point
   05-31-2007 · EurekAlert!
   NASA and Columbia University Earth Institute research finds that human-made greenhouse gases have brought the Earth's climate close to critical tipping points, with potentially dangerous consequences for the planet.
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5. MERLIN TIMI-36 study provides new safety and efficacy data for unique anti-anginal therapy
   03-27-2007 · EurekAlert!
   Chest pain due to a shortage of blood in the heart, known as angina, is a condition that affects millions of Americans. The most recently approved new pharmaceutical approach to treat chronic angina is a novel drug called ranolazine, which was approved in 2006 for use as second line therapy in patients who continue to experience angina despite treatment with another class of anti-anginal medication.
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6. New approaches to endometriosis treatment -- mouse experiments point the way
   07-02-2007 · EurekAlert!
   Possible new directions for the treatment of endometriosis, a painful condition associated with infertility that affects up to 15 percent of women of reproductive age, will be outlined in the presentation of two experimental studies at the 23rd annual conference of the European Society of Human Reproduction and Embryology (Tuesday July 3). Both concern targeting angiogenesis -- the formation of new blood vessels -- which is encourages endometriosis by providing a rich blood supply.
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7. Gene Signatures Match Cancer And Other Diseases With Potentially Effective Drugs
   09-29-2006 · ScienceDaily
   In one of the most ambitious spinoffs of the human genome project, researchers at Dana-Farber Cancer Institute, Children's Hospital Boston, the Broad Institute of Harvard and MIT, and other collaborating centers have unveiled a new, systematic approach to drug discovery that matches diseases with potential treatments using a universal language based on cells' distinctive gene activity profiles, or "signatures."
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8. Quantum effects writ large
   02-15-2007 · EurekAlert!
   A team of physicists from Rice University, Rutgers University, and the Max Planck Institute for Chemical Physics of Solids in Dresden, Germany, reports this week in the journal Science the discovery of surprising quantum effects in a member of a broad class of materials that include high-temperature superconductors and quantum magnets. The effects were observed at a "quantum critical point," a tipping point at which the quantum properties of the material undergo a radical change.
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9. UC Santa Barbara scientists clarify molecular basis of interferon action
   07-19-2007 · EurekAlert!
   Scientists at the University of California, Santa Barbara have made a significant discovery relating to viral infections in humans. They studied how a certain enzyme called PKR behaves in human cells, and showed that this enzyme is important for the antiviral effect of interferon against some viruses, but not others. Interferon is a naturally occurring substance that is also used as a drug to treat certain viruses such as Hepatitis C.
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10. UF researchers track genetic journey of HIV from birth to death
    10-16-2007 · EurekAlert!
    University of Florida researchers tracked four children born with HIV, studying blood samples taken at birth, throughout life and just after death. Using a high-resolution computational technique, they monitored protein mutations. Previous studies relied on cell culture or animal models to follow the virus' mutations over time. The UF researchers are among the first groups to study the progression of HIV in human patients.
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