**BIOTECH AND PHARMA NEWS** - Page 77 - iHUB Organization

Preciouslife1 · 11-20-2007, 10:48

Quark Pharmaceuticals Inc. (QURK) Announces First Systemic siRNA Dosing in Humans Commences Phase I Clinical Trial of Proprietary siRNA Molecule in Acute Renal Failure

http://www.clinicaspace.com/news_story.aspx?NewsEntityId=77923

FREMONT, Calif., Nov. 19 /PRNewswire/
Quark Pharmaceuticals, Inc., a development-stage pharmaceutical company focused on discovering and developing novel RNA interference-based therapeutics, announced today that it has commenced systemic dosing in humans of its proprietary product candidate, AKIi-5, a siRNA compound discovered and developed by Quark for the treatment of Acute Renal Failure (ARF), also called Acute Kidney Injury (AKI). Based on publicly available information, Quark believes that this is the first human clinical trial involving the systemic delivery of siRNA.

The Phase I clinical trial is a multi-center, double-blind, placebo controlled, dose-escalation trial assessing the safety and pharmacokinetics of AKIi-5 administered intravenously as a single dose to patients undergoing major cardiac surgery. Patients will be enrolled in the trial in a number of centers in the United States, Europe and Israel. Quark expects to complete the trial in early 2008. Depending on the results of this trial, Quark expects to initiate a dose-ranging Phase II clinical trial measuring AKIi-5 clinical activity.

Daniel Zurr, Chief Executive Officer, commented, "The initiation of human dosing in our Phase I trial in ARF signifies a very important step in Quark's clinical program and marks an important milestone in the RNAi industry. For Quark, the trial serves to further validate the strength of our pipeline and our overall expertise in the RNAi arena. With AKIi-5 now in the clinic, RTP801i-14, which we licensed to Pfizer, in a Phase I/IIa clinical trial for the treatment of wet age-related macular degeneration, AHLi-11 in IND-enabling studies and additional RNAi-based candidate drugs in pre-clinical testing, we believe Quark has one of the most robust RNAi product portfolios in the industry.

"For the RNAi industry, the trial may be even more noteworthy as it represents the first documented systemic dosing of siRNA in humans. While the science of RNAi has been well-established, a key step in the acceptance of the technology as a promising therapeutic is the ability to deliver RNAi-based compounds systemically. We look forward to leading this important advance for the industry and, at the same time, continuing the development of this and other siRNA products in our pipeline."

Quark was granted an IND by the Food and Drug Administration (FDA) for AKIi-5 for the prevention of Acute Renal Failure in high-risk patients undergoing major cardiovascular surgery. AKIi-5 is a synthetic, chemically modified siRNA molecule discovered and patented by Quark that has an AtuRNAi technology-based structure licensed from Silence Therapeutics. Quark has also licensed certain intellectual property from Alnylam.

Quark has conducted pre-clinical studies of AKIi-5 for the prevention of acute renal failure in rats and monkeys. Rats treated with a single bolus injection of AKIi-5 were significantly protected from ischemia/reperfusion- induced acute kidney injury. In the rat studies, AKIi-5 effectively prevented the development of acute renal failure. Quark's pharmacokinetic, distribution, and toxicity studies in rats and monkeys indicate that AKIi-5 appears to have a favorable safety profile and has a relatively short residence time in the kidney.

About AKIi-5

AKIi-5 is a synthetic, chemically modified siRNA molecule designed to temporarily inhibit the expression of p53, a gene which plays a significant role in ARF by inducing tubular cell death (apoptosis) in response to injury. AKIi-5 is based on Quark's proprietary, patented concept of temporary and reversible inhibition, for therapeutic purposes, of the expression of the transcription factor human p53, which is associated with DNA repair and apoptosis.
The concept was first published by Quark with the University of Illinois in a breakthrough paper in Science magazine (Science. 1999 Sep 10;285). Using RNA interference technology to temporarily inhibit p53 in acute settings such as acute kidney injury, apoptosis is delayed thereby allowing natural repair mechanisms to restore normal DNA and cellular integrity.

About Acute Renal Failure (ARF) / Acute Kidney Injury (AKI)

ARF is a syndrome characterized by a rapid decline of kidney function leading to death in a high percentage of cases. Major cardiac surgery is one of the many causes of ARF. During cardiac bypass surgery, lack of oxygen caused by reduced local blood flow to the kidneys, followed by rapid reintroduction of oxygen, or reperfusion, to the kidneys upon removal of the patient from cardiopulmonary bypass, initiates a chain of events that can lead to ARF. Currently, there are no approved drug therapies that effectively prevent or treat ARF.

About Quark Pharmaceuticals, Inc.

Quark Pharmaceuticals, Inc. is a development-stage pharmaceutical company focused on discovering and developing novel therapeutics based on its proprietary gene discovery science and technology, with an initial focus on drug candidates that work through the natural mechanism in the cell known as RNA interference, or RNAi, for the treatment of diseases associated with oxidative stress. Quark believes that its proprietary target gene discovery platform, BiFARTM, combined with its ability to design and successfully deliver synthetic molecules of the new class of RNAi therapeutics known as small-interfering RNA, or siRNA, to specific organs in the body, enables the Company to rapidly develop drug candidates. Quark has two internally discovered and developed clinical stage lead product candidates: RTP801i-14 in phase I/IIa clinical trial for the treatment of wet age-related macular degeneration, and AKIi-5 in phase I for the prevention of acute renal failure both of which have an AtuRNAi technology-based structure licensed from Silence Therapeutics, as well as a license from Alnylam. The Company has licensed RTP801i-14 to Pfizer on an exclusive worldwide basis. Quark has, in addition, a product candidate portfolio of RNAi therapeutics based on novel targets and therapeutic concepts discovered using BiFAR(TM) and designed for the treatment of oxidative stress associated diseases of the inner ear, lungs and additional organs of the body.

Quark is headquartered in Fremont, California and operates research and development facilities in Boulder, Colorado and Ness-Ziona, Israel. Additional information is available at www.quarkpharma.com

Preciouslife1 · 11-20-2007, 10:49

Review Publication Confirms the Benefits of Highly Effective Oral Cancer Drug Xeloda(R) (capecitabine) Over Intravenous Chemotherapy in Advanced Breast Cancer

PR Newswire Europe (inc. UK Disclose) - Nov. 20, 2007

Annals of Oncology Paper Suggests That Oral Agents Such as Xeloda, Which are Proven to be Equally Effective and Have a Tolerable Side Effect Profile, Should Replace Traditional Intravenous Chemotherapy.

A review paper in Annals of Oncology now published on-line concludes that the oral cancer drug Xeloda (capecitabine) offers an effective and more cost- effective treatment option than current intravenous (iv) cytotoxic chemotherapy treatments for patients with advanced breast cancer. This treatment also results in fewer days spent in hospital to manage adverse events when compared to iv therapy.

The paper in the Annals of Oncology includes a recent study comparing first-line capecitabine versus the well-known chemotherapy combination of cyclophosphamide, methotrexate and 5-FU (CMF). Women receiving capecitabine lived significantly longer than those receiving this traditional iv chemotherapy regimen. Further information on this trial presented recently showed that as well as extending the life expectancy of these women, their quality of life was better with capecitabine than with traditional iv CMF (1).

However, there is growing consensus that oral therapies should only replace iv alternatives when they have demonstrated at least equ.ivalent efficacy and that tolerability is not compromised. 82% of US Oncologists interviewed in a survey stated that their key consideration in selecting an oral chemotherapy agent was efficacy at least eq.uivalent to iv alternatives (2).

According to the review, chemotherapy treatment for cancer has traditionally been dominated by intravenous drug therapies, despite their considerable impact on patients' lives. The time and money spent travelling to, waiting for, and receiving treatment at a clinic can place a major burden on patients, preventing them from spending precious time with their family and friends. In rural or remote areas, intravenous chemotherapy is particularly difficult because patients may live hours away from their nearest clinic.

"Traditionally, oncologists have favoured intravenous chemotherapy as they have had more confidence in efficacy with its minimal bioavailability and patient compliance problems and because intravenous chemotherapy had an established reimbursement framework." said Professor Michael Findlay, University of Auckland, New Zealand, and lead author of the article. "However, with the progressive evidence indicating particular oral chemotherapy drugs have eq.uivalent or superior efficacy oncologists are increasingly integrating these drugs into their practice. Capecitabine particularly has established a place as an oral chemotherapy of choice in breast cancer both as a single agent and as a component of a drug combination."

Unlike traditional chemotherapies, capecitabine targets the cancer cells directly, with less impact on healthy cells. Capecitabine has an unusual safety profile, characterised by gastrointestinal toxicities and hand-foot syndrome, but has a particularly low incidence of hair loss or decreased production of blood cells and platelets.

Pharmacoeconomic studies (3),(4) also suggest that in pretreated patients with me.tastatic breast cancer, capecitabine as a monotherapy is more cost-effective than intravenous comparator therapies (e.g. infused 5-FU, gemcitabine, or vinorelbine). NICE approved capecitabine as a cost effective option for me.tastatic breast cancer in March 2003.

The authors conclude that the most important characteristic of a chemotherapeutic agent is efficacy. Once efficacy is uneq.quivocally established, the development and refinement of oral chemotherapy treatments like capecitabine are likely to offer numerous benefits to patients, oncologists, oncology nurses, pharmacists and healthcare providers.

About Xeloda

Xeloda is licensed in more than 100 countries worldwide including the EU, USA, Japan, Australia and Canada and has been shown to be an effective, safe, and convenient oral chemotherapy in treating over 1.4 million patients to date.

Roche received marketing authorisation for Xeloda as a first-line monotherapy (by itself) in the treatment of me.tastatic colorectal cancer (colorectal cancer that has spread to other parts of the body) in most countries (including the EU and USA) in 2001. Xeloda has also been approved by the European Medicines Agency (EMEA) and U.S. Food and Drug Administration (FDA) for adjuvant (post-surgery) treatment of colon cancer in March and June 2005, respectively.

Xeloda is licensed in combination with Taxotere (docetaxel) in women with me.tastatic breast cancer (breast cancer that has spread to other parts of the body) and whose disease has progressed following i.v. chemotherapy with anthracyclines. Xeloda monotherapy is also indicated for treatment of patients with me.tastatic breast cancer that is resistant to other chemotherapy drugs such as paclitaxel and anthracyclines. Xeloda recently received approval in South Korea for the first-line treatment of patients with locally advanced (me.tastatic) pancreatic cancer, in combination with gemcitabine. Xeloda is licensed in South Korea for the first-line treatment of stomach cancer, and has recently received EU approval for the first-line treatment of advanced stomach cancer in combination with a platinum agent.

The most commonly reported adverse events with Xeloda include diarrhoea, abdominal pain, nausea, stomatitis and hand-foot syndrome (palmar-plantar erythrodysesthaesia).

Preciouslife1 · 11-20-2007, 10:53

Viral Vertigo/HCV

Forbes - Nov. 26, 2007
http://www.therapeuticsdaily.com/news/article.cfm?***********************************typ e=sentryarticle&********************************** *value=1611184&channelID=31

A drug for stealth killer hepatitis C has been years in the making. Hopes for a blockbuster are feverish.
If you want to know why drug research remains a slow and frustrating business even in this golden age of molecular biology, look at the troubles Vertex Pharmaceuticals has gone through to devise a new drug to combat hepatitis C.

Hep C chronically infects 3.2 million Americans. The liver disease is spread through direct contact with tainted blood. Most people don't know they have it because the disease can lie dormant for decades. It now kills 10,000 each year, but the death toll could soar.

Vertex has a drug in the pipeline called telaprevir that it hopes will be the first in a new, more powerful generation of hep C treatments.Really, tell us more, haha!!
Telaprevir is a protease inhibitor that attacks the virus directly and blocks its replication, much the way antiretrovirals revolutionized the treatment of AIDS over a decade ago.
Existing hep C treatments, based on bioengineered versions of the natural immune system protein alpha interferon, attack the virus indirectly and work half the time, at best, for the most common strain. The side effects--fever, fatigue and anemia--are so bad that many patients forgo treatment, rolling the dice that their livers won't fail.

Vertex, an 18-year-old firm in Cambridge, Massachusetts, has always been on the cusp of having a big-selling drug yet has never quite scored with one. A lot of hopes are riding on telaprevir. Midstage trial data revealed this month showed that telaprevir, when combined with existing drugs, cleared the virus in 61% of patients in the U.S. and 65% of patients in Europe; it did this in 24 weeks, versus 48 weeks needed for existing therapies.

The drug is clearly effective, but there were a lot of buts the day the data came out. Wall Street knocked the stock down 9%. The results were at the low end of investor expectations, says Cowen & Co. And a company called Romark Laboratories has come out of nowhere with data on an unheralded anti-parasite drug that seems effective on one hep C strain.

At least two years of trials remain before any of the new drugs hit the market. Sanford C. Bernstein projects annual sales of hep C drugs will surge from $2.5 billion today to $11 billion in 2012. Vertex could snag a chunk of that--if its drug is safe and effective. Four other hep C drugs suffered setbacks this year. Vertex's stock sank 13% on Oct. 18 when Schering-Plough touted promising results for its rival protease inhibitor.

Vertex has already surmounted an array of problems since it started working on hep C in 1993. It took two years to get a stable crystalline form of the hepatitis C protease enzyme for study. Once this was done, "it became clear what a remarkable challenge" designing a protease inhibitor would be, says Vertex executive John Thomson. Most enzymes have grooves that druglike chemicals can snuggle into, blocking their function. The surface of the hepatitis C protease turned out to be flat. Finding a drug that would stick was akin to climbing a sheer cliff with no cracks. The company had to engineer a chemical by mimicking the enzyme's target. It took another three years to figure out a way to grow the virus in a test tube, a requirement for testing an antiviral.

Doctors hope, ultimately, to boost cure rates by combining protease inhibitors with a second drug class called polymerase inhibitors. Roche, one of several firms in the polymerase hunt, just unveiled data showing its drug helped eliminate signs of the virus in the blood in 81% of patients after an initial four weeks of treatment; dosing is continuing to see if the drug can keep the virus away.

One or more of the new compounds are likely to work. "We are going to have much higher response rates in the very near future. It is going to blow the market wide open," predicts Mount Sinai School of Medicine's Douglas Dieterich, who is testing the Roche compound.

Preciouslife1 · 11-20-2007, 10:53

Health Canada Licenses QIAGEN's New Molecular Test for Hepatitis B

Hugin - Nov. 20, 2007

The Company's artus HBV LC PCR Kit improves treatment of HBV infections by monitoring patients' viral load

VENLO, The Netherlands / GERMANTOWN, Md., November 20, 2007 - QIAGEN today announced that its newly released hepatitis B virus (HBV) assay kit is in compliance with Health Canada's medical device requirements. The artus HBV LC PCR Kit, which monitors the viral load of HBV infected patients, is now available to doctors in Canada to help them determine the success of a treatment.

The ready-to-use molecular diagnostic detection kit for the quantitation of hepatitis B viral DNA from plasma helps to monitor on-going drug therapy treatments for those people chronically infected with hepatitis B. The kit utlilizes the polymerase chain reaction (PCR) amplification technology and is configured for the widely available LightCycler Instrument. The kit provides all necessary reagents optimized for reliable HBV DNA detection and quantitation - including of the HBV genotypes A-G. This spectrum of genotypes is representative of strains of the virus which can be found globally, ensuring highest sensitivity in monitoring of treatments.

"QIAGEN is pleased to have gained compliance from Health Canada. We look forward to making our new HBV assay kit available to our customers and thereby to patients chronically infected with hepatitis B in Canada," said Doug White, Senior Vice President Sales and Marketing for the Americas. "The artus HBV kit will play an important role in assisting healthcare workers in monitoring hepatitis B patients' viral load. This is extremely important for the implementation and administration of successful therapy."

The hepatitis B virus affects millions of people worldwide.

Hepatitis B is a serious disease caused by a virus that, among others, attacks the liver. The virus can cause cirrhosis of the liver, liver cancer, liver failure, and even death. The virus is mostly transmitted through blood transfusions, unprotected sexual contact, needle-stick injuries, shared or re-used needles and from infected mothers to newborn babies during birth. Most infected adults are able to fight off the hepatitis B virus. However, some adults and most infected babies and children are unable to rid their bodies of the virus, and develop chronic infections.

QIAGEN has the broadest offering of molecular diagnostic tests in the world. The Company is currently seeking further pre-market approvals and clearances in the United States and medical device licenses in Canada to offer its customers in North America more solutions for use in clinical applications. QIAGEN today sells a number of products approved or cleared for in-vitro diagnostic use in the United States, including the only FDA approved test for the human Papillomavirus, which plays a key role in cervical cancer screening and prevention.

The QIAamp DSP Virus Kit DNA isolation method has been validated for use with the artus HBV LC PCR Kit.

The artus HBV LC PCR Kit is not intended for use as a screening test for blood or blood products for the presence of HBV or as a diagnostic test to confirm the presence of HBV infection.

Trademarks: QIAGEN, artus (QIAGEN Group); LightCycler (Roche Group).

About QIAGEN QIAGEN N.V., a Netherlands holding company is the leading provider of innovative sample and assay technologies and products. QIAGEN's products are considered standards in areas such pre-analytical sample preparation and assay solutions in research for life sciences, applied testing and molecular diagnostics. QIAGEN has developed a comprehensive portfolio of more than 500 proprietary, consumable products and automated solutions for sample collection, nucleic acid and protein handling, separation, and purification and open and target specific assays. The company's products are sold to academic research markets, to leading pharmaceutical and biotechnology companies, to applied testing customers (such as in forensics, veterinary, biodefense and industrial applications) as well as to molecular diagnostics laboratories. QIAGEN employs more than 2,600 people worldwide. QIAGEN products are sold through a dedicated sales force and a global network of distributors in more than 40 countries.

Further information about QIAGEN can be found at www.qiagen.com.

Preciouslife1 · 11-20-2007, 10:55

BIOWORLD Today - Nov. 20, 2007

http://www.therapeuticsdaily.com/news/article.cfm?***********************************typ e=sentryarticle&********************************** *value=1611111&channelID=31

Abbott, of Abbott Park, Ill., said the European Committee for Medicinal Products for Human Use has issued a positive opinion recommending approval of Humira (adalimumab) for the treatment of moderate to severe plaque psoriasis. Psoriasis will be the fifth disease indication for HUMIRA. Humira was developed by the former Cambridge Antibody Technology, of Cambridge, UK, now part of MedImmune Inc.

Alios BioPharma Inc., of South San Francisco, and the Cleveland Clinic today announced that they have entered into an exclusive worldwide license agreement focused on development of small-molecule RNase L activators for the treatment of a broad range of viral diseases such as chronic hepatitis B and hepatitis C, HIV, influenza and others. The technology also is applicable to the treatment of cancer for both solid tumors and hematological malignancies such as leukemia. The agreement grants Alios exclusive worldwide rights to Cleveland Clinic patents, technology and preclinical small molecules relating to RNase L activation. Under the terms of the agreement, Alios will provide the Cleveland Clinic an up-front license fee, various development, regulatory and commercial milestones, and royalties on net sales. In addition, Alios will sponsor ongoing research at the Cleveland Clinic for a period of two years. Alios will continue the research and development of those compounds with the goal of advancing molecules toward clinical development for both chronic and acute viral diseases and for cancer. The agreement covers the use of RNase L activators for all human, veterinary and agricultural applications. Financial terms were not disclosed.

Argos Therapeutics Inc., of Durham, N.C., said it has granted exclusive research and development rights based on its regulatory T-cell technology to Johnson & Johnson subsidiary Therakos Inc., of Exton, Pa. Terms of the agreement were not disclosed.

DeCODE genetics, of Reykjavik, Iceland, launched deCODEme, a service that enables individuals to get a detailed look at their own genome. Subscribers who send a cheek swab can learn what their DNA reveals about ancestry, body traits and genetic variants associated with higher or lower average risk of disease. The information will be continually updated as new discoveries are made.

Discovery Laboratories Inc., of Warrington, Pa., said the FDA has accepted the firm's Nov. 1 submission as a complete response to the April 2006 approvable letter for Surfaxin (lucinactant), natural human lung surfactant with KL-4 peptide, for the prevention of respiratory distress syndrome in premature infants. The FDA set May 1, 2008 as its target date to complete its review of the new drug application for the product.

DSM Pharmaceutical Products, of Parsippany, N.J., and Crucell NV, of Leiden, the Netherlands, have granted licensing rights for their PER.C6 cell line to Daiichi Sankyo, of Tokyo. Financial terms of the agreement were not disclosed.

Endo Pharmaceuticals Inc., of Chadds Ford, Pa., and Penwest Pharmaceuticals Co., of Danbury, Conn., said they have filed a lawsuit against Impax Laboratories Inc., of Hayward, Calif., in the U.S. District Court for the District of Delaware related to Impax's abbreviated new drug application for Opana ER (oxymorphone HCl) extended-release tablets CII. The lawsuit alleges infringement of certain Orange Book-listed U.S. patents that cover the Opana ER formulation. It also seeks a declaratory judgment stating that Impax has no legitimate basis to trigger the Hatch-Waxman ANDA patent litigation process because the FDA has rescinded its acceptance of the application.

GeoPharma Inc., of Largo, Fla., disclosed second-quarter results for its reporting period ending September 30, listing total revenues of $6 million compared to $6.8 million in the first quarter. The firm, which has won approval of its first generic drug, the veterinary product carprofen, said it is making progress on 12 ANDAs and other drugs in the pipeline.

Helix BioPharma Corp., of Aurora, Ontario, said that the firm's CEO position will no longer be jointly held by Donald Segal and John Docherty. Segal will assume the role of CEO, and Docherty will take the position of president. Segal is a founding partner, and Docherty joined the company in 1999.

Humanetics Corp., of Minneapolis, said Congress has awarded the company an additional $3.8 million from the fiscal year 2008 Defense Appropriations Act, signed by President Bush. This award to Humanetics brings the total funding received by the company from the Department of Defense to slightly less than $7 million. The 2008 funding will be used by Humanetics to continue development, clinical testing, regulatory approval, manufacturing and commercialization of a number of medical radiation countermeasures. The firm's lead candidate, BIO 300, is undergoing large animal efficacy and human safety trials. The company also is working with several preclinical lead candidates which are showing promising early results.

Inflazyme Pharmaceuticals Ltd., of Vancouver, British Columbia, said its shareholders approved the sale of the majority of its research and development assets to Biolipox AB, of Stockholm, Sweden. Of the votes cast, 98 percent voted for the sale. In return for the sale, which includes the PDE inhibitors, the LSAIDs and the Protein Therapeutics technology, Inflazyme receives $4 million in cash and up to $7 million in potential milestones plus royalty payments, which include $1.5 million upon a decision to enter a Phase IIb clinical study with a PDE inhibitor; $2.5 million upon a decision to initiate a Phase III study with a PDE inhibitor; $3 million upon a decision to begin a Phase III clinical study with an LSAID; and a royalty of 1.25 percent on net sales of the first PDE inhibitor commercialized. Inflazyme also may receive up to 35 percent of the proceeds from the subsequent sale or licensing of the Protein Therapeutics technology if that happens within 12 months of the asset sale.

Schering-Plough Corp., of Kenilworth, N.J, said it has received antitrust clearance from the U.S. Federal Trade Commission for its planned acquisition of Organon BioSciences NV, of Oss, the Netherlands, from Akzo Nobel NV, of Amsterdam, the Netherlands. The $14.4 billion acquisition was announced in March. Schering-Plough still needs to secure certain regulatory approvals, including clearance from the U.S. Federal Trade Commission but expects the transaction to be completed by year-end. Separately, Schering-Plough said that the European Commission approved the 48-week standard dose of Pegintron (peginterferon alfa - 2b, 1.5 mcg/kg once weekly) and Rebetol (ribavirin, 800 - 1,400 mg daily) combination therapy for retreating adult patients with chronic hepatitis C whose prior treatment with interferon alpha (pegylated or nonpegylated) and ribavirin combination therapy or interferon alpha monotherapy did not result in a sustained response.

Singulex Inc., of Hayward, Calif., signed a collaboration with researchers at Washington University School of Medicine in St. Louis to increase the clinical utility of validated and recently discovered biomarkers in human disease. Singulex also said the firm will get a $900,000 Phase I/II Fast Track Small Business Innovation Research contract from the National Cancer Institute to create biomarker assays to help predict patient response and therapeutic efficacy of cancer therapies in development. Scientists at Washington University will be part of Singulex's Erenna Technology Access Program (ETAP) to develop biomarker assays for both validated and putative biomarkers in important disease areas, including breast cancer, Alzheimer's disease, diabetes and stroke. ETAP allows early access for institutions and companies to Erenna, the company's biomarker detection platform system, which incorporates biomarker detection and optimized immunoassays.

ThromboGenics NV, of Leuven, Belgium, said it has begun preclinical development of an anti-VPAC antibody for thrombocytopenia. Thrombocytopenia, which is the reduced number of platelets in blood, is a common severe side effect of chemotherapy and increases the risk of bleeding and severity of hemorrhage. Researchers at the University of Leuven and ThromboGenics have developed a novel therapeutic approach, showing that the inhibition of VPAC could stimulate the production of platelets. VPAC is a receptor present at the surface of bone marrow cells called megakaryocytes, which, when mature, produce platelets.

UCB SA, of Brussels, Belgium, said it has been informed by the European Medicines Agency that the Committee for Medicinal Products for Human Use adopted a negative opinion on the market authorization application in the European Union for Cimzia (certolizumab pegol) in the treatment of patients with Crohn's disease. UCB plans to appeal, and a decision is expected during the first half of 2008. Cimzia is a pegylated anti-TNF, for which UCB filed a biologics license application in early 2006. The drug was approved in Switzerland for Crohn's disease in September of this year, and UCB said preparation for a U.S. regulatory submission for Cimzia in treating rheumatoid arthritis is ongoing.

Preciouslife1 · 11-20-2007, 10:56

Concealment Of Tumours From Immune System The Focus Of New Research

http://www.medicalnewstoday.com/articles/89334.php

Scientists studying how immune cells are regulated in healthy individuals, have made a key discovery in understanding why tumours may go undetected by the immune system and remain untreated by the body's own natural defences. The findings, published online this week (between 19 - 23 November) by the Proceedings of the National Academy of Sciences, could lead to new treatments for tumours.

Under normal circumstances, the immune system creates sustained inflammation around a dangerous pathogen or injury which tells the body that there is a problem. However, in the case of tumours, certain cellular mechanisms counteract inflammation which can cause the tumour to go undetected, making it even harder for the body to expel.

The researchers at King's College London, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), discovered that regulatory T cells can reverse the role of a key immune cell called a macrophage which is normally involved in causing inflammation. Regulatory T cells are cells that regulate the immune system to stop it over-responding to every external stimulus and only deal with genuinely harmful pathogens or injuries. The research shows that they can achieve this by encouraging macrophages to instead dampen down the inflammatory response that is automatically induced by all possible threats to the body, even those that turn out to be harmless.

Dr Leonie Taams, research leader explains: "A relatively harmless stimulus, such as a small cut, will automatically be treated by the body as something dangerous and will cause macrophages to promote inflammation. We discovered that it is then the regulatory T cells' responsibility to make the macrophages promote anti-inflammation to counteract the initial response, as it is not a real danger. This helps keep the immune system stable and prevents the body over-reacting to everything in its environment.

"However problems can occur with tumours, where many regulatory T cells promoting a strong anti-inflammatory response are present. Neutralising an inflammatory response in this scenario can cause the tumour to fall under the radar of the body's immune system and 'trick' it into believing that there is no problem.

"We hope to be able to use this new knowledge about the relationship between regulatory T cells and macrophages to find more effective treatments for tumours. Interestingly, we also hope to use the same knowledge to achieve the opposite result and block chronic inflammation such as that which occurs in rheumatoid arthritis."

Preciouslife1 · 11-20-2007, 10:56

Concealment Of Tumours From Immune System The Focus Of New Research

http://www.medicalnewstoday.com/articles/89334.php

Scientists studying how immune cells are regulated in healthy individuals, have made a key discovery in understanding why tumours may go undetected by the immune system and remain untreated by the body's own natural defences. The findings, published online this week (between 19 - 23 November) by the Proceedings of the National Academy of Sciences, could lead to new treatments for tumours.

Under normal circumstances, the immune system creates sustained inflammation around a dangerous pathogen or injury which tells the body that there is a problem. However, in the case of tumours, certain cellular mechanisms counteract inflammation which can cause the tumour to go undetected, making it even harder for the body to expel.

The researchers at King's College London, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), discovered that regulatory T cells can reverse the role of a key immune cell called a macrophage which is normally involved in causing inflammation. Regulatory T cells are cells that regulate the immune system to stop it over-responding to every external stimulus and only deal with genuinely harmful pathogens or injuries. The research shows that they can achieve this by encouraging macrophages to instead dampen down the inflammatory response that is automatically induced by all possible threats to the body, even those that turn out to be harmless.

Dr Leonie Taams, research leader explains: "A relatively harmless stimulus, such as a small cut, will automatically be treated by the body as something dangerous and will cause macrophages to promote inflammation. We discovered that it is then the regulatory T cells' responsibility to make the macrophages promote anti-inflammation to counteract the initial response, as it is not a real danger. This helps keep the immune system stable and prevents the body over-reacting to everything in its environment.

"However problems can occur with tumours, where many regulatory T cells promoting a strong anti-inflammatory response are present. Neutralising an inflammatory response in this scenario can cause the tumour to fall under the radar of the body's immune system and 'trick' it into believing that there is no problem.

"We hope to be able to use this new knowledge about the relationship between regulatory T cells and macrophages to find more effective treatments for tumours. Interestingly, we also hope to use the same knowledge to achieve the opposite result and block chronic inflammation such as that which occurs in rheumatoid arthritis."

Preciouslife1 · 11-21-2007, 00:47

A Protein Coordinates The Daily Cycles Of Oxygen-Carrying Heme Molecules To Maintain The Body's Correct me.tabolism, Researchers Find

It's well known that the body's energy levels cycle on a 24-hour, or circadian, schedule, and that this me.tabolic process is fueled by oxygen. Now, researchers at the University of Pennsylvania School of Medicine have found that a protein called Rev-erb coordinates the daily cycles of oxygen-carrying heme molecules to maintain the body's correct me.tabolism.

The research appears online this week in Science Express in advance of print publication in Science.

Many studies, including this one, point to a link between the human internal clock and such me.tabolic disorders as obesity and diabetes. Proteins such as Rev-erb are the gears of the clock and understanding their role is important for fighting these diseases.

"This is the next chapter on Rev-erb, a member of a family of cell-nucleus proteins that includes receptors for anti-diabetic drugs," explains senior author Mitchell A. Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and me.tabolism at Penn. About two years ago Lazar's group discovered that Rev-erb was a critical component of the circadian clock. In this paper, they found that the activity of Rev-erb is controlled by heme.

Heme represents the body's most important way of transporting and using oxygen, which would simply bubble away in the body without being bound to heme. "In a molecular baton hand-off, oxygen is transferred from heme in the bloodstream to the heme molecules found inside a cell," says Lazar, of how oxygen reaches cells to run their me.tabolic needs. One of the most important roles of heme inside cells is to facilitate the use of oxygen to generate energy in the process known as cellular respiration.

The findings further tie together the 24-hour cycle of the body with me.tabolic function. "Circadian rhythms are our sleep-wake cycle and me.tabolism is how we process food, so it makes sense that there would be biological cross-talk between the body's 24-hour rhythm and me.tabolic function," says Lazar. Indeed, scientists already recognize that getting too much or too little sleep increases the risk of diabetes. The newly discovered circadian/me.tabolic link could be the focus of a new generation of diabetes treatments.

The Penn group worked with scientists at GlaxoSmithKline, who demonstrated that the Rev-erb protein can physically bind to heme in the test tube. The Penn scientists then found that heme, by regulating the activity of Rev-erb, reduces the amount of glucose produced by liver cells.

"What's exciting about this is that it puts heme in a central role in the me.tabolic regulation of the cell," says Lazar. "Not only is it a key component in making energy, but also in the pathway for turning off glucose production." Excessive glucose production by the liver is a major cause of high blood sugar in diabetes.

This work was funded by the National Institute of Diabetes and Digestive and Kidney Disease. Co-authors are first author Lei Yin, Joshua C. Curtin, Mohammed Qatananai, and Nava R. Szwergold, all from Penn and Robert A. Reid, Gregory M. Waitt, Derek J. Parks, Kenneth H. Pearce, and G. Bruce Wisely, from GlaxoSmithKline, Research Triangle Park, NC.

This release is available at http://www.pennhealth.com/news

PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #3 in the nation in U.S. News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals -- its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center -- a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

Preciouslife1 · 11-21-2007, 00:51

Stress Hormone May Hasten The Progression Of Certain Blood Cancers
Main Category: Endocrinology News

Researchers here have shown that in cell cultures, the stress hormone norepinephrine appears to promote the biochemical signals that stimulate certain tumor cells to grow and spread.

The finding, if verified, may suggest a way of slowing the progression and spread of some cancers enough so that conventional chemotherapeutic treatments would have a better chance to work.

The study also showed that stress hormones may play a completely different role in cancer development than researchers had once thought.

The results appear in the current issue of the journal Brain, Behavior and Immunity.

"We would not be surprised if we see similar effects of norepinephrine on tumor progression in several different forms of cancer," explained Eric Yang, first author of the paper and a research scientist with the Institute for Behavioral Medicine Research (IBMR) at Ohio State University.

Yang and colleague Ron Glaser, a professor of molecular virology, immunology and medical genetics, last year showed that the stress hormone norepinephrine was able to increase the production of proteins in cultures of nasopharyngeal carcinoma tumor cells that can foster the aggressive spread of the disease, a process known as me.tastasis. Glaser is director of the IBMR and a member of the Comprehensive Cancer Center at Ohio State.

In this latest study, the researchers looked at a different type of cancer multiple myeloma. One of several types of cancers of the blood, multiple myeloma strikes nearly 20,000 Americans each year, killing at least half that many annually. Patients diagnosed with this disease normally survive only three to four years with conventional treatments.

Yang and Glaser focused on three multiple myeloma tumor cell lines, each representing a different stage in the life of the disease, for their experiments. While all three tumor cell lines reacted to the presence of norepinephrine, only one, a cell line known as FLAM-76, responded strongly to the hormone.

The norepinephrine binds to receptors on the surface of the cells, sending a signal to the nucleus to produce a compound known as VEGF -- vascular endothelial growth factor that is key to the formation of new blood vessels, which the tumor must have to grow.

The FLAM-76 cell line was prepared from multiple myeloma tumor cells taken from a patient whose disease had not yet progressed too far from its original site in the bone marrow where blood cells are formed.

"It turns out that FLAM-76 tumor cells more closely represent the earlier stages of the disease when blood vessel formation, a process called angiogenesis, is needed for disease progression," Yang said.

"The fact that this one cell line, of the three multiple myeloma cell lines studied, closely represents the early stages of the tumor, and that this is where we see the biggest effect, is what makes this work more clinically relevant," Glaser said.

The researchers believe that blocking these receptors would slow the process of the growth of more blood vessel to the tumor, delaying disease progression and perhaps allowing treatments to be more effective. Widely used "beta-blocker" drugs now prescribed for high blood pressure work by blocking these same particular cell surface receptors, Yang said.

"This approach wouldn't kill the tumor cells but it would diminish the blood supply to the tumor cells and slow them down, and that could translate into a longer and better quality of life for the patient," Glaser said.

The researchers and their colleagues are now working with other forms of cancer to test the effects of stress hormones like norepinephrine on their growth.

Glaser added that these kinds of results may change the way scientists are looking at a link between stress and the development and spread of cancer. In the past, he said, the focus was on how stress hormones weakened the immune system, allowing certain tumors to evade the body's defenses.

"Now we have these stress hormones, not only affecting the immune response, but also acting directly on the tumor cells and inducing changes in the molecules made by those same tumor cells," Glaser said.

"This has important implications for the spread of the tumor and me.tastasis."

Elise Donovan, a researcher with the IBMR, and Don Benson, a researcher with Ohio State's Comprehensive Cancer Center, also worked on the project. The research was funded in part by the National Cancer Institute.

Ohio State University
1125 Kinnear Rd.
Columbus, OH 43212-1153
United States
http://www.osu.edu

Preciouslife1 · 11-21-2007, 06:14

New Way To Prevent Protein Plaques Implicated In Alzheimer's Found

http://www.medicalnewstoday.com/articles/89159.php

For reasons unknown, amyloid beta, a protein, aggregates into toxic plaques in the brain, destroying neurons. These plaques are one of the hallmarks of Alzheimer's disease. Now two new animal studies show for the first time that the deadly transformation of amyloid beta into plaques can be prevented through an interaction between amyloid beta and another protein called cystatin C.

Although much work needs to be done, these new findings may open the door to new treatments for Alzheimer's disease that mimic the effects of cystatin C, says Efrat Levy, Ph.D., Associate Professor in the Departments of Psychiatry and Pharmacology at New York University School of Medicine, and the lead author of the study. "We are really excited by these findings because recent studies show that cystatin C is protective against a variety of insults that cause cell death in the brain. Our potential therapeutic approach focuses on keeping amyloid beta in a water soluble form, preventing its accumulation in the brain, and thus slowing, halting, or reversing disease progression," says Dr. Levy, who is also Director of the Laboratory of Molecular Pathology of Cerebral Amyloidosis at the Nathan S. Kline Institute for Psychiatric Research in Orangeburg, New York.

With support from the Alzheimer's Association, Dr. Levy's laboratory has already begun studies to develop a drug that will mimic the ability of cystatin C to bind to a non-pathological form of amyloid beta and thereby prevent its accumulation into plaques in the brain.

Alzheimer's is estimated to affect 5 million Americans and there are no medicines that can delay or prevent the disease. Many laboratories worldwide are pursuing ways to prevent the clumping of amyloid beta as possible therapies for the disease.
It isn't known whether the protein actually causes Alzheimer's, but amyloid beta is one of the proteins implicated in the disease process.

The two studies appear in the on-line November 18, 2007, edition of the journal Nature Genetics and will be published in its December 2007 issue.

The first study was performed by Dr. Levy in collaboration with other investigators at the Nathan S. Kline Institute for Psychiatric Research and New York University School of Medicine. The second study was performed by Dr. Levy and colleagues in the laboratory of Dr. Mathias Jucker at the Hertie-Institute for Clinical Brain Research in Tubingen, Germany.

Both studies used mice that were genetically engineered to produce human cystatin C as well as abundant amounts of amyloid beta plaques in their brains. The cystatin C bound to the soluble, non-pathological form of amyloid beta in these mice and inhibited the aggregation and deposition of amyloid beta plaques in the brain.

The research shows that cystatin C binds soluble amyloid beta also in the human brain, and suggests that this binding inhibits its aggregation into insoluble plaques in humans, says Dr. Levy. Cystatin C production and body fluid levels vary among healthy individuals and can be influenced by certain hormones, aging, and certain pathological conditions, she says. Furthermore, it was recently demonstrated that a genetic variation in the cystatin C gene in human populations is linked to a greater risk of developing Alzheimer's disease during aging.

These findings suggest, says Dr. Levy, that even subtle modifications of cystatin C protein levels could affect amyloid beta accumulation and deposition in the brain, thereby modifying disease progression.

Cystatin C is found in all body fluids and tissues of mammals. It is a jack-of-all-trades, playing a broad role in many functions, including cell proliferation and growth, modulation of the inflammatory response, and bone resorption. The protein also has been implicated in neuronal degeneration and repair of the nervous system.

"The work of Dr. Levy and colleagues offers important insights into how cystatin C may lower the risk for Alzheimer's disease, setting the stage for a new approach to therapy," said Ralph A. Nixon, M.D., Ph.D., Professor of Psychiatry and Cell Biology at NYU School of Medicine and Director of the Center for Dementia Research at the Nathan S. Kline Institute. Dr. Nixon also directs the Silberstein Institute at NYU School of Medicine.

"Given the increasing prevalence of this disease, its staggering social and economic costs for patients and their families, and the limitations of existing therapies, we are very hopeful that this research will lead to improved medications to prevent the disease and forestall its devastating symptoms," said Dr. Harold S. Koplewicz, Director of the Nathan S. Kline Institute, and the Chair of the Department of Child and Adolescent Psychiatry and a Vice-Dean at NYU School of Medicine.

New York University Medical Center and School of Medicine
__________________

Preciouslife1 · 11-21-2007, 06:27

Students' Genomics Tool Will Lead To Better Medicine
Main Category: Genetics News

http://www.medicalnewstoday.com/articles/89262.php

While consumers and pharmacists are well aware that prescription drug interactions can be dangerous, the fact that each person's genetic makeup can render certain drugs dangerous or even deadly is not widely recognized.

Students in Purdue University's Department of Computer and Information Technology are working to develop an information-management tool that could give pharmacists instant access to patients' genetic profile, making it possible to quickly determine the proper medicine dosage or if the drug cannot be tolerated by the patient.

"Toxicity due to a person's genetic tolerance for certain drugs is the primary reason that prescription drugs are pulled off the market," said Michael D. Kane, an assistant professor in the department and lead genomic scientist at Bindley Bioscience Center in Purdue's Discovery Park. "Even though drugs are tested extensively, some people don't me.tabolize drugs in the same way, leading to underdosing, or worse, overdosing and toxicity.

"There currently is no way for doctors and pharmacists to access and make sense of this information, so what we are doing could drastically improve patient safety and care in coming years."

A patient's genetic profile would be one factor in determining drug type and dosage, along with commonly used factors such as weight, gender, general health and interactions with other drugs the patient may be taking.

If a patient is prescribed a drug where an adverse response has been associated with a specific genetic makeup, the patient's electronic health record would indicate that the patient is at risk for an adverse reaction. Kane said that in some cases certain patients may not be prescribed a drug at all or the dosage may need to be adjusted.

"Right now, the only way a person's reaction to a drug can be determined is by starting them on a low dose, then adjusting and testing as needed," he said. "If we can use genetics to make this known immediately, we can save a lot of time and money."

Kane said students are using real clinical data to create a mock patient population that harbors genetic predispositions for altered drug me.tabolism. Using common database and software development tools, student-designed systems will be evaluated by practicing pharmacists, ultimately to provide training for fifth-year pharmacy students, practicing pharmacists and health-care professionals.

Although the practice of genetic screening across the population is not common now, technological developments and the medical benefits derived from having genetic information on file will likely make the process cheaper and more common, Kane said.

"Genetic testing relevant to pharmacogenetics is available now, but it costs hundreds of dollars per patient.
And if you take that information to your doctor or pharmacist, they would have no idea what it means in terms of disease or drug me.tabolism," he said. "That is why we are using real data to develop a system that is quick and easy to use and can translate this information for health-care professionals."

Kane said the data that will be kept in such a database would be secure and would initially contain genetic information only as it relates to drug me.tabolism, not risk of disease, which is the basis of pharmacogenetics.

"Some people may be concerned about their having genetic information in a database, but what health-care professionals will have access to is not information on how likely a patient is to develop specific health disorders," he said.
"Having this genetic-drug interaction information available will actually benefit the patient, employer and insurance provider since overall health-care costs would be minimized by avoiding adverse drug reactions."

Kane said taking genetic information into account when developing new drugs also would lead to a more efficient and specialized drug-development process.

"For instance, if a company makes a drug for a condition like schizophrenia, it may work on only a third of the population. If we have data based on genetic information, however, that company may be able to make three slightly different drugs, and nearly all of the population would be able to take one of them," Kane said. "That would mean more profits for the company and more safety and less frustration for the patient."

Kane said information about who can genetically tolerate certain medications is already included in the drug information literature available to doctors and pharmacists on some drugs, and he predicts it will be a widespread practice within a decade.

"Using genetic information in this way is a novel and exciting idea," he said. "This really is the future of medicine. Our next step will be to focus on how to train health-care professionals."

Kane is collaborating on this project with John A. Springer, an assistant professor of computer and information technology at Purdue, and Jon E. Sprague, dean of the College of Pharmacy and a professor at Ohio Northern University.

http://www.purdue.edu

Preciouslife1 · 11-21-2007, 06:32

Monkeys Able To Fend Off AIDS Like Symptoms With Enhanced HIV Vaccine
Main Category: HIV / AIDS News
Article Date: 21 Nov 2007 - 0:00 PST

http://www.medicalnewstoday.com/articles/89419.php

Researchers at the University of Pennsylvania School of Medicine have discovered that using an immune system gene to enhance a vaccine used to study HIV in macaque monkeys provides the animals with greater protection against simian HIV (SHIV) than an unmodified vaccine. This multi-year study found that the addition of a molecule called Interleukin-15 effectively boosts the effects of a vaccine derived from the DNA of simian HIV. The study illustrates that DNA vaccine effectiveness can be improved by the inclusion of specific immune adjuvants, or helpers.

The findings are published in last week's online edition of the Proceedings of the National Academy of Sciences.

"DNA vaccine technology has great promise for the development of vaccines and immune therapeutics for a variety of infectious diseases and cancers," says senior author David B. Weiner, PhD, Professor of Pathology and Laboratory Medicine at Penn. While previous studies have established that the technology can induce immune responses safely, "improving the immune potency of this platform is critical for further development in humans."

The research builds on previous work aimed at engineering a more potent immune response to SHIV DNA vaccine technology. Mouse model studies previously showed that the cytokine IL-15 -- a substance that can improve the body's natural response to infection and disease -- helps better immune responses and protection, while this study mirrors those findings in a larger, non-human primate species.

In this study, the group of macaques that was injected with the vaccine containing a loop of DNA enabling them to make IL-15 developed no signs of AIDS-like symptoms when exposed to live SHIV, compared to four animals in the control group that received only the DNA vaccine. The modified vaccine appeared to help suppress viral replication among the IL-15 group.

Next, Weiner's team will study the protected macaques to determine the actual mechanism of their protection, and seek out any pockets of the virus that may be hiding in specific immune compartments. The approach will also be tested for safety and immunogenicity in humans through the HIV Vaccine Trials Network.

The lead author of the study is Dr. Jean Boyer, of the University of Pennsylvania. Co-authors include researchers from the National Cancer Institute, the Southern Research Institute in Frederick, MD, the National Institute of Allergy and Infectious Diseases in Bethesda, MD, Genomix (San Diego, CA) and Wyeth (Pearl River, N.Y.). The research was supported by the National Institutes of Health and the Intramural Research Program of the NIH.

PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
http://www.med.upenn.edu

Preciouslife1 · 11-21-2007, 07:10

How Tumors Go Undetected By The Body

http://www.sciencedaily.com/releases/2007/11/071119213955.htm

Scientists studying how immune cells are regulated in healthy individuals, have made a key discovery in understanding why tumours may go undetected by the immune system and remain untreated by the body's own natural defences. The findings could lead to new treatments for tumours.

Under normal circumstances, the immune system creates sustained inflammation around a dangerous pathogen or injury which tells the body that there is a problem. However, in the case of tumours, certain cellular mechanisms counteract inflammation which can cause the tumour to go undetected, making it even harder for the body to expel.

The researchers at King's College London, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), discovered that regulatory T cells can reverse the role of a key immune cell called a macrophage which is normally involved in causing inflammation. Regulatory T cells are cells that regulate the immune system to stop it over-responding to every external stimulus and only deal with genuinely harmful pathogens or injuries.

The research shows that they can achieve this by encouraging macrophages to instead dampen down the inflammatory response that is automatically induced by all possible threats to the body, even those that turn out to be harmless.

Dr Leonie Taams, research leader explains: "A relatively harmless stimulus, such as a small cut, will automatically be treated by the body as something dangerous and will cause macrophages to promote inflammation. We discovered that it is then the regulatory T cells' responsibility to make the macrophages promote anti-inflammation to counteract the initial response, as it is not a real danger. This helps keep the immune system stable and prevents the body over-reacting to everything in its environment.

"However problems can occur with tumours, where many regulatory T cells promoting a strong anti-inflammatory response are present. Neutralising an inflammatory response in this scenario can cause the tumour to fall under the radar of the body's immune system and 'trick' it into believing that there is no problem.

"We hope to be able to use this new knowledge about the relationship between regulatory T cells and macrophages to find more effective treatments for tumours. Interestingly, we also hope to use the same knowledge to achieve the opposite result and block chronic inflammation such as that which occurs in rheumatoid arthritis."

This research was published online the week of 19 - 23 November by the Proceedings of the National Academy of Sciences

Preciouslife1 · 11-21-2007, 07:18

Breakthrough opens door to organ transplants grown in lab

Agence France-Presse English Wire - Nov. 21, 2007
by Mira Oberman

CHICAGO, Nov 20, 2007 (AFP) - Transplantable hearts grown in petri dishes and the regeneration of amputated limbs were once the things of science fiction.

But a major breakthrough brought those dreams closer to reality Tuesday after researchers announced they were able to turn the clock back on skin cells and transform them into stem cells, the mutable building blocks of organs and tissues.

"This is truly the Holy Grail: To be able to take a few cells from a patient -- say a cheek swab or few skin cells -- and turn them into stem cells in the laboratory," Robert Lanza of Advanced Cell Technology told AFP.

"It's bit like learning how to turn lead into gold."

While the research is still in its infancy, the potential benefits are "tremendous" said Lanza, who has already found ways to cut the death rate following heart attacks in half, restore blood to limbs which would otherwise have to be amputated and construct a functioning kidney using stem cells.

The use of skin cells will eventually allow doctors to create stem cells with a specific patient's genetic code, eliminating the risk that the body would reject transplanted tissues or organs.

It also will lead to a virtual explosion in the availability of research materials used to test new drugs and understand how diseases like cancer, diabetes and Alzheimer's function.

That's because stem cells are able to infinitely replicate themselves and can be turned into any of 220 different types of cells in the human body.

But access to stem cells has been restricted because of the complications, both and technical, of harvesting human embryos.

The new technique, while far from perfected, is so promising that the man who managed to clone the world's first sheep, Dolly, is giving up his work cloning embryos to focus on stem cells derived from skin cells.

"The fact that (the) introduction of a small number of proteins into adult human cells could produce cells that are equ.ivalent to embryo stem cells takes us into an entirely new era of stem cell biology," said Ian Wilmut, the Scottish researcher who first created a viable clone by transferring a cell nucleus into a new embryo.

"We can now envisage a time when a simple approach can be used to produce stem cells that are able to form any tissue from a small sample taken from any of us."

One of the greatest advantages of the new technique is its simplicity: it takes just four genes to turn the skin cell back into a stem cell.

This, unlike the complex and expensive process developed by Wilmut, can be done in a standard biological lab. And skin cells are much easier to harvest than embryos.

The main hurdle to overcome is finding a safe way to transform the skin cells.

The current method, developed by two teams of researchers in the United States and Japan, raises the risk of cellular mutation because a retrovirus was used deliver four genes to the cell.

While this will delay the use of these stem cells in treatment, it won't stop researchers from using the cells to study diseases and develop drug treatments.

Prior to this discovery, researchers who wanted to look at how diseases developed would usually have to study animals or organs harvested from cadavers because embryonic stem cells were so hard to use and access.

"It's an explosion of resources," said Konrad Hochedlinger, of the Harvard Stem Cell Institute.

"You can take skin cells from a diabetic, turn them into pancreatic cells and figure out what happens," he said in a telephone interview.

These stems cells could allow researchers to map the genetic structure of diseased cells, a process which could unlock a cure.

They could also allow researchers to do chemical screens to identify drugs which may cure or treat the disease, a process which could significantly speed up the process of bringing life-saving drugs to the market.

US-Japan-health-science-stemcell

Preciouslife1 · 11-23-2007, 08:36

Positive Outcome of Drug-Drug Interaction Trial With Intravenous Iclaprim

PR Newswire Europe (inc. UK Disclose) - Nov. 21, 2007

REINACH, Switzerland, November 21 /PRNewswire-FirstCall/
Arpida Ltd announced today the results of a Phase I trial investigating the possible interaction between intravenous iclaprim and warfarin. Warfarin is widely used for the prophylaxis of thrombosis and embolism and its dosing needs to be well-controlled.The drug-drug interaction study comprised 24 healthy volunteers and was performed in Germany.
Dosing of warfarin with and without pre- and co-administration of iclaprim (1.6 mg/kg infused over 60 minutes) was investigated.

Administration of intravenous iclaprim at this supra-therapeutic dose was assessed to be safe for clinical applications. It had no significant effect on the pharmakonetics and pharmacodynamics of warfarin.
Moreover, the trial results again confirm the good safety and tolerability profile of iclaprim.

Dr Paul Hadvary, Head of Development of Arpida Ltd., commented: "The results of this Phase I study are very positive, showing that iclaprim has no significant effect on the pharmacokinetics of warfarin, which is widely used in the targeted patient population. The results expand the experience gathered in an earlier Phase I study in which the interaction between ketaconazole and iclaprim was investigated. In summary, iclaprim's drug-drug interaction profile looks favourable.
This is of great importance as iclaprim is expected to be administered to patients with significant co-morbidities and receiving several other medications. These Phase I data add substantial weight to the NDA package that we intend to file shortly with the U.S. Food and Drug Administration for intravenous iclaprim in its first indication: complicated Skin and Skins Structure Infections (cSSSI)."

About Arpida Ltd.

Arpida is a biopharmaceutical company with research facilities near Basel, Switzerland and in the USA. It focuses on the discovery and development of novel drugs that seek to overcome the growing problem of microbial resistance. The most advanced compounds include an antibacterial close to NDA-filing and an antifungal in Phase III.

Arpida's leading product candidate is intravenous iclaprim, a potent, pathogen-focused, late-stage antibiotic that targets severe infections requiring hospital treatment, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). The US Food and Drug Administration has granted fast track status to intravenous iclaprim. In March 2007, Arpida completed patient enrolment in the second pivotal Phase III trial in complicated skin and skin structure infections. The top-line data of the second trial were reported in July 2007. An NDA filing is expected to take place in the second half of 2007.

In June 2007, Arpida announced that it has received approval from the US FDA to initiate Phase II trials with intravenous iclaprim in the treatment of patients with hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) or healthcare associated pneumonia (HCAP).

An oral formulation of iclaprim has successfully completed three Phase I trials: an ADME study (absorption, distribution, ********************bolism and excretion) with radiolabelled compound, a Phase I bioavailability trial with a solution and one with a capsule formulation. Iclaprim could be offered not only as an intravenous therapy for hospital use in acute situations, but also as an oral formulation, allowing early patient discharge followed by outpatient treatment. This switch should be a valuable instrument in reducing healthcare costs and enhancing patient comfort.

Arpida's fourth most advanced antibiotic programme, AR-709, targets upper and lower respiratory tract infections acquired in the community setting. AR-709 exhibited potent activity against a large panel of pneumococcal clinical isolates including those resistant to currently used drugs. Promising results of "first-in-man" studies with AR-709 were published in March 2007.

An additional compound, AR-2474, has achieved in vivo proof of concept. AR-2474 has been shown to be highly effective in eradicating pathogens in preclinical models of skin infection and nasal carriage.

Apart from the antibiotic programmes, Arpida has an innovative antifungal therapy (TLT) which is about to enter Phase III clinical trials in Europe, targeting onychomycosis.

Moreover, the company has several other leads in optimisation and additional discovery programmes derived from its own discovery platform at various research stages.