Microbially Derived Artemisinin Highlighted In American Journal Of Tropical Medicine And Hygiene’s Special Malaria Supplement

The Institute for OneWorld Health (iOWH), the US-based non-profit pharmaceutical company that develops drugs for people with infectious diseases in the developing world, announced that an article describing groundbreaking research in semisynthetic artemisinin has been published in the American Journal of Tropical Medicine and Hygiene’s (AJTMH) special malaria burden supplement Defining and Defeating the Intolerable Burden of Malaria III: Progress and Perspectives.

The article, Microbially Derived Artemisinin: a Biotechnology Solution to the Global Problem of Access to Affordable Antimalarial Drugs, was co-authored by OneWorld Health Founder and Board Chair Victoria Hale, Ph.D., and Artemisinin Project partners Jay D. Keasling, Ph.D., of the University of California Berkeley, Neil Renninger, Ph.D., of Amyris Biotechnologies and Thierry T. Diagana, formerly of OneWorld Health and now with the Novartis Institute for Tropical Diseases. The article can be found online here.

“OneWorld Health, Amyris, and U.C. Berkeley are pleased to contribute to this important body of work that is shedding a light on efforts to combat malaria,” said Dr. Hale. “It is critical for the global health community to share research, findings and innovations as we work together to eradicate this devastating disease.”

The article describes efforts to develop semisynthetic artemisinin through a partnership among OneWorld Health, Amyris Biotechnologies and U.C. Berkeley. The Bill & Melinda Gates Foundation awarded OneWorld Health a five-year grant of $42.6 million in December 2004 to manage the research and development collaboration, which is using synthetic biology to develop a new, low-cost technology platform for producing artemisinin and its derivatives. The goal of the collaboration is to create a consistent, high-quality and affordable new source of artemisinin, a key ingredient for making life-saving anti-malarial drugs know as artemisinin-based combined therapies (ACTs). Participation in the collaboration reflects OneWorld Health’s participation in the global effort to eradicate malaria.

The World Health Organization recommends using ACTs as first line treatment for malaria in regions where the usual first-line treatments for malaria are no longer effective because of increasing drug resistance. The commercial-scale productivity of semisynthetic artemisinin technology has the potential to supplement existing plant-derived materials with a new low-cost, high-quality source of artemisinin and thus to help meet the projected world-wide demand for ACTs. Lowering artemisinin production costs with new technologies should also improve the artemisinin supply so that ACT prices fall significantly. Diversifying the sources of artemisinin will help stabilize supplies, preventing cyclical fluctuations in artemisinin prices. To make more affordable ACTs, other supply chain problems such as stability, leakage to unregulated markets, counterfeiting, distribution, and private sector regulation must also be addressed.

More than 40 percent of the world’s population live in areas where malaria is endemic. The disease is responsible for more than one million deaths annually and between 350 and 500 million people fall ill to malaria each year. One in five childhood deaths in Africa are due to malaria and the majority of the disease burden is carried by children under five and pregnant women in rural and impoverished regions.

Defining and Defeating the Intolerable Burden of Malaria III: Progress and Perspectives is intended to create awareness of the continued need for funding and research to combat malaria and strengthen the capacity of scientists and institutions to address the burden of the disease through the research and development of science-based policies and interventions in the endemic countries. The AJTMH supplement is available at no charge in paper, on CD-Rom, and online here.

About the Institute for OneWorld Health

The Institute for OneWorld Health, the first US nonprofit pharmaceutical company, develops safe, effective and affordable new medicines for people with infectious diseases in the developing world. The Institute for OneWorld Health, headquartered in San Francisco, California, USA, is a tax-exempt 501 (c) (3) US corporation.

Institute for OneWorld Health

Autologous Induced Pluripotent Stem Cells And Gene Repair Therapy For Treatment Of Familial Hypercholesterolemia

Study shows, for the first time, the successful reprogramming of diseased human hepatocytes into induced pluripotent stem cells (iPSC).1

Results also found differentiation into mature hepatocytes was more efficient than that with fibroblast-derived iPSCs.

The generation of diseased hepatocyte-derived human iPSC lines provides a good basis for the study of liver disease pathogenesis.

Such technology could give a potentially unlimited reservoir of cells for the treatment of human liver diseases: generating genetically corrected liver cells via auto-transplantation of genetically modified hepatocytes, thus avoiding liver transplant and lifelong immunosuppression.

References:

1 Bosman, A. et al. Progress toward the clinical application of autologus induced pluripotent stem cells and gene repair therapy for treatment of familial hypercholesterolemia. Abstract presented at The International Liver CongressTM 2011.

Source:
Travis Taylor

European Association for the Study of the Liver

Genes Causing Antimalarial Drug Resistance Identified By Researchers

Using a pair of powerful genome-search techniques, researchers from the Harvard School of Public Health (HSPH), Harvard University, and the Broad Institute have identified several genes that may be implicated in the malaria parasite’s notorious ability to rapidly evade drug treatments. Further testing revealed that one of the genes, when inserted into drug-sensitive parasites, rendered them less vulnerable to three antimalarial drugs.

The successful experiments suggest that the genomic methods are useful tools for probing the genetic mechanisms underlying drug resistance in the Plasmodium falciparum malaria parasite and potentially other types of disease-causing parasites as well.

The study appears online April 21, 2011, in PLoS Genetics, and is timed to coincide with World Malaria Day on April 25.

“Identification of mutations associated with drug resistance helps us understand how the parasite evades the effects of the drug,” said Sarah Volkman, senior research scientist at HSPH and a co-senior author of the paper. “Once we understand the processes used by the parasite to avoid the effects of the antimalarial treatment, scientists can develop new drugs that circumvent the strategies employed by the drug-resistant malaria parasite.”

In addition, said Volkman, knowing the mutations that signal that a parasite has become resistant to an antimalarial compound allows researchers to develop tools that can be used for monitoring and surveillance of drug-resistant parasites.

Reducing the toll of malaria, which kills nearly a million people a year – mainly young children in sub-Sahara Africa – is a major challenge because of the parasite’s talent for swiftly developing resistance to multiple drugs. To counter the shape-shifting parasite’s defenses, scientists say they must improve on their meager understanding of the molecular and genetic mechanisms of resistance.

Genetically diverse populations of the blood-borne malaria parasite are endemic in Africa, Asia, and South America. When exposed to antimalarial drugs and the human immune system, Plasmodium falciparum has a remarkable ability to quickly generate resistant clones of parasites, a major obstacle to successful treatment.

For the study, the scientists, including Volkman, Dyann Wirth, and co-first author Daria Van Tyne of HSPH and the Broad, co-first author Danny Park and Pardis Sabeti of the Broad and Harvard University, and Daniel Neafsey and Stephen Schaffner of the Broad, analyzed the DNA of 57 parasites from the three continents, using a high-density genome-wide array that examines more than 17,000 mutations. They also measured the parasites’ responses to 13 antimalarial drugs.

The scientists examined diversity of the parasite to identify 20 rapidly evolving loci in the genome, and then carried out a genome-wide association study (GWAS) to identify genetic variants that correlated with or are associated with the drug-resistance trait. These genetic variants are necessarily enriched in the drug-resistant, but not drug-sensitive parasites, allowing the researchers to home in on the candidate genes that are involved in modulating drug responses. That search netted 11 genes implicated in drug resistance – one previously known and others discovered for the first time.

Van Tyne pursued one of the novel genes, PF10_0355, for follow-up functional testing. She used an experimental technique that introduced extra copies of the gene from a resistant parasite into a drug-sensitive one, and found that the formerly sensitive parasite was now rendered more resistant to three standard antimalarial agents.

“This demonstration suggests that the gene is involved in modifying parasite drug response,” said Van Tyne, a graduate student in the laboratory of Wirth, chair of the Department of Immunology and Infectious Diseases at HSPH and a co-director of the Infectious Disease Initiative at the Broad. “We feel that this is one gene of potentially many that affect drug-resistance mechanisms. We’re now working to follow up and understand how these and the other genes identified work.”

Drug resistance is a major concern that threatens to undermine global efforts to control or eradicate malaria. Understanding how the parasite is changing before clinical drug resistance is apparent offers some hope that we might be able to extend the useful life of available drugs and identify new effective antimalarials, said Volkman.

Notes:

The study was funded by the Bill and Melinda Gates Foundation, the Ellison Medical Foundation, the ExxonMobil Foundation, the Fogarty International Center at the NIH and the National Institute of Allergy and Infectious Diseases.

“Identification and Functional Validation of the Novel Antimalarial Resistance Locus PF10_0355 in Plasmodium Falciparum,” Daria Van Tyne, Daniel J. Park, Stephen F. Schaffner, Daniel E. Neafsey, Elaine Angelino, Joseph F. Cortese, Kayla G. Barnes, David M. Rosen, Amanda K. Lukens, Rachel F. Daniels, Danny A. Milner, Jr., Charles A. Johnson, Ilya Shlyakhter, Sharon R. Grossman, Justin S. Becker, Daniel Yamins, Elinor K. Karlsson, Daouda Ndiaye, Ousmane Sarr, Souleymane Mboup, Christian Happi, Nicholas A. Furlotte, Eleazar Eskin, Hyun Min Kang, Daniel L. Hartl, Bruce W. Birren, Roger C. Wiegand, Eric S. Lander, Dyann F. Wirth, Sarah K. Volkman, Pardis C. Sabeti, PLoS Genetics, online April 21, 2011

Source:
Todd Datz
Harvard School of Public Health

п»їп»їRethink Lodges Complaint Over Frankie Boyle Sketch

Mental health charity Rethink has lodged a complaint with Ofcom over a sketch by comedian which parodied attempts to tackle stigma around mental illness.

Boyle, who is also under fire from AIDS and cancer charities over his television show, mocked an advert produced by the Time to Change anti-stigma project, which is run by Rethink and Mind.

The project, which is funded by Comic Relief and the Big Lottery Fund, has succeeded in changing attitudes around mental health and in reducing discrimination.

In part it seeks to tackle the stereotype which associates violence with mental illness and challenges the image of the ‘violent schizophrenic’ in movies, by producing a trailer for a fake horror film called ‘Schizo’ which leads the viewer into expecting a stereotyped view of schizophrenia. Ultimately the film shows someone with schizophrenia talking about their experiences while making tea in his kitchen.

In the Frankie Boyle sketch, shown on the Channel 4 show ‘Tramadol Nights’, a man says he has mental health problems and comments on the stigma surrounding mental illness. The camera then pans down to show four children dead and covered in blood.

Stuart Baker-Brown, 46, the actor in the original TTC video ‘Schizo’, was diagnosed with schizophrenia in 1996 and has since recovered.

Stuart said: “Stigma and discrimination can be just as harmful as the destructive symptoms of mental illness itself and this sketch can do nothing but cause further harm. It is a shame Frankie Boyle has to act in such an insensitive and unintelligent manner towards those who suffer deeply and towards those who are far less fortunate than himself.”

In a letter to Ofcom, Mark Davies, Rethink’s director of communications said: “There is no causal link between mental illness and violence. In fact, people with mental illness are more likely to be the victims than the perpetrators of violence.

“Clearly, given that someone like Mr Boyle feels the need to mock the Time to Change project, we must be succeeding in at least raising the issue to a wider audience.

“But we cannot ignore the fact that this sort of thoughtless, insensitive stereotyping of difficult human experiences in the name of comedy blights the lives of those seeking to overcome mental illness.

“Rethink fully supports freedom of expression, but we do believe the line must be drawn somewhere. Prejudice and discrimination around mental illness is one of the last taboos in our society and we are determined to do everything we can to tackle it.

“By inferring that people with mental illness are violent, the Frankie Boyle sketch was misleading. One in four people have a mental health problem at some point in their lives. This sketch caused offence to many people in this group.”

Violence and particularly homicide by people with mental illness is a very tiny proportion of violent crime and is exceptionally rare.

A recent study estimated that, across the world, approximately one case occurred per every 14 million people per year.[1] To put this in context, only 4.3% of homicides of strangers between 1996 and 1999 were carried out by people with a diagnosis of schizophrenia.[2]

Rethink is a national mental health charity and the largest voluntary sector provider of mental heath services in England, representing people with schizophrenia, bipolar disorder and other mental illnesses.

Notes:

[1] Criminal offending in schizophrenia over a 25-year period marked by deinstitutionalization and
increasing prevalence of co morbid substance use disorders. (2004) Wallace C et al, Am J Psychiatry
161 (4):716-727

[2] Mental illness in people who kill strangers: longitudinal study and national clinical survey. Shaw J,
Amos T, Hunt I, et al. BMJ. 2004;328:734-737.

Source:
Rethink

Massive Smoke Clouds Emanating From Fires Around Moscow

Space scientists at the University of Leicester have released satellite images of vast plumes of smoke emanating from the peat bog fires which are currently sweeping across central and western Russia.

Using equipment on the European satellite MetOp-A researchers from the University’s Earth Observation Science group have analysed and released still images taken on 4, 8 and 9 August.

Each satellite image is available as both a true colour image and as a false colour version in which the smoke shows up as yellow. Using this technique, the extent of the smoke plumes and their encirclement of Moscow becomes obvious.

As well as demonstrating the massive extent of the smoke clouds across Western Russia, the satellite images indicate another interesting phenomenon: pyrocumulonimbus clouds. These are water clouds, caused by hot air rising directly from a fire, which can trap airborne pollution and transport it for thousands of kilometres. The image from 8 August clearly shows these clouds moving towards Finland in the extreme top left of the picture.

Dr David Moore from the Earth Observation Science Group said,: “Using measurements from spaceborne instruments, we have been able to observe the vast extent of the smoke released from numerous wildfires in Western Russia. The pollutants contained within these smoke plumes can have a profound effect on both the local and regional air quality and atmospheric chemistry. A key aspect of our ongoing investigations will be to quantify the impact the fires have had on indirect greenhouse gases in the atmosphere, such as carbon monoxide.” Here is an enhanced true color image for Aug. 4.

The Earth Observation Science (EOS) group is based in the University of Leicester’s Space Research Centre and includes staff from the Department of Physics and Astronomy, the Department of Chemistry and the Department of Geography. Earlier this year the EOS group released satellite images of the volcanic ice clouds which enveloped Europe after an eruption in Iceland. Here is a false color image from August 4 which highlights the smoke from the wildfires as bright yellow.

Source:
Dr David Moore
University of Leicester

HPV Infection Highly Prevalent Among Organ Transplant Recipients

A new study published in the American Journal of Transplantation reveals an association between the human papillomavirus (betaPV) infection and cutaneous squamous cell carcinoma (SCC) in organ transplant recipients.

HPV is known to cause cervical cancer and SCC in the anogenital area and also plays a role in some forms of head and neck cancer. SCC skin cancer is increasing in incidence worldwide and the risk is particularly high in immunosuppressed individuals such as organ transplant recipients in whom rates are 100 times those of the general population.

Researchers led by Jan Nico Bouwes Bavinck and Mariet Feltkamp of Leiden University Medical Center, studied a total of 210 organ transplant recipients with previous SCC and 394 controls without skin cancer. They used cutting-edge technologies to assess the presence of 25 betaPV types in plucked eyebrow hairs with simultaneous detection of antibodies to these viruses in blood.

Results show that BetaPV infection is highly prevalent in organ transplant recipients; 94% of patients without skin cancers carried DNA in eyebrow hairs and 97% in those with a history of skin cancer. Furthermore, concordant presence of DNA and antibodies to the same beta HPV type is associated with increased risk for SCC skin cancer.

“Carriage of beta HPV types (a particular skin group of HPV viruses) is extremely common in immunosuppressed individuals,” Feltkamp notes. “Our research findings help to provide a clearer picture of the specific HPV types that may play a part in causing SCC which ultimately may lead to novel preventative or therapeutic interventions.”

Full citation: Feltkamp et al. A Case-Control Study of Betapapillomavirus Infection and Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients. American Journal of Transplantation; See here.

About the Author: Mariet Feltkamp, MD, PhD, is affiliated with Leiden University Medical Center.

Source:

Wiley-Blackwell

Use Of Information Technology Is Minimal In Nursing Homes

In short-term health care settings, sophisticated information technology (IT) systems assist in the diagnosis of patients, support care management, and enhance adherence to clinical guidelines. However, current levels of IT sophistication in U.S. nursing homes are unknown. In response to recent efforts from policy makers to integrate IT in long-term health care, a University of Missouri researcher found, through two different studies, that the current level of IT use in Missouri nursing homes is minimal.

“IT sophistication has been studied extensively in acute care settings, but until these studies, IT has not been measured in long-term care settings. We found many different types of technology being used in nursing homes,” said Greg Alexander, professor in the MU Sinclair School of Nursing. “While some homes have advanced systems that aid nurses in making treatment decisions, wireless technology to assist in the delivery of care, and systems that support administrative and financial matters and inpatient self-management, the majority of Missouri nursing homes have minimal levels of technology in place.”

According to Alexander, most agencies that advocate for wider uses of technology have overlooked nursing homes, despite the growing recognition that a stronger IT infrastructure is needed to address the complex health care needs of nursing home residents and improve the quality of care delivered in these facilities.

Recent concerns about errors in health care and patient safety have prompted policy makers and government committees to recommend the development of technologies to support clinical decision making and promote data standards. These recommendations also include designing systems that are able to communicate with each other. The Institute of Medicine recently released a report outlining the level of diversity and maturity of technology expected in nursing homes by 2010.

“These initial studies reveal that nursing home administrators have a long way to go before they achieve the goals suggested by the IOM report,” Alexander said. “The development of IT profiles is a necessary first step toward benchmarking the best practices of IT use across nursing homes in the United States. The next step is to continue this study in other Midwest states and, eventually, in every state.”

Alexander said the goal is to create a national infrastructure for health care providers that will enable the exchange of information between short-term care and long-term care facilities. Advancing technology will allow providers to coordinate and transfer work between settings as patients are relocated from one facility to another.

###

Source:
Emily Smith
University of Missouri-Columbia

CytRx’s Arimoclomol Demonstrates Statistically Significant Neurorestorative Results In A Preclinical Embolic Stroke Trial

CytRx Corporation (NASDAQ:CYTR), a biopharmaceutical company engaged in the development and commercialization of human therapeutics, announced data from an animal stroke trial indicating that treatment with its molecular chaperone amplifier drug candidate, arimoclomol, initiated at either six, 10, 24 or 48 hours post-stroke, demonstrated neurorestorative ability based on multiple behavioral tests measuring motor and sensory recovery.

“We believe the data from this trial confirm and extend previous highly favorable preclinical results indicating that arimoclomol has the potential to restore brain function following stroke, even when administered well beyond the three-hour therapeutic window of t-PA, the currently approved treatment for stroke,” said CytRx President and CEO Steven A. Kriegsman. “If efficacious in stroke patients, we believe arimoclomol would represent a major breakthrough in improving their quality of life. Due to the compelling nature of this opportunity we have had pre-IND discussions with the U.S. Food and Drug Administration (FDA) concerning a possible IND application necessary to initiate a Phase 2 human stroke trial with arimoclomol. We are also working with the FDA to potentially resume Phase 2 testing with arimoclomol as a therapeutic treatment for ALS, and we do not believe that the current clinical hold on that trial will impact the ability to initiate human testing in stroke recovery. We continue to compile a very compelling data set with arimoclomol in stroke recovery as we actively seek a partner to sponsor future clinical development of this promising drug candidate.”

Stroke is caused by a lack of blood flow, most usually caused by an embolism (blood clot), and results in a lack of oxygen to regions of the brain. In the United States alone, stroke affects about 700,000 persons each year. On average, every 40 seconds someone in the United States has a stroke, and stroke is the leading cause of serious, long-term disability, according to the American Heart Association. Currently, t-PA is the only FDA-approved treatment and must be administered within three hours of the initiation of stroke.

CytRx scientists used the embolic animal model in the stroke trial as it closely mimics part of the typical human stroke pathology, particularly the clot formation in cerebral vessels that stop or slow blood flow to effect damage. Over time these clots in the embolic animal model, as in humans, can spontaneously dissolve, resulting in restoration of partial blood flow to the damaged regions. This rapid “reperfusion” of oxygen-rich blood is known to contribute to some of the long-term damage that occurs during stroke.

In the study, stroke was induced in 10 rats in each group through the introduction of blood clots into the middle cerebral artery, blocking blood flow to parts of the brain and causing cerebral oxygen deprivation. These stroke-induced rats then received an oral dose of arimoclomol or a control substance daily for 28 days after stroke with the initial dose being withheld until 6, 10, 24, or 48 hours after stroke. Sensorimotor impairment was evaluated by three different tests given before stroke and again at intervals after stroke.

In one functional test, a statistically significant improvement in stroke recovery was observed for all arimoclomol-treated groups regardless of when treatment was initiated. In the two other tests, a statistically significant improvement was observed in the groups treated at six, 10 and 24 hours after stroke was induced. The assessment of the remaining group, treated at 48 hours after stroke, showed a trend for improvement that did not reach statistical significance in these latter two tests.

“t-PA works as a fibrolytic (‘clot buster’), to restore blood flow as quickly as possible,” stated Jack Barber, Ph.D., CytRx’s Chief Scientific Officer. “Arimoclomol instead apparently acts by restoring (repairing) the proper functioning of the nerve cells previously damaged by oxygen deprivation, allowing it to be therapeutic even when administered at later times after stroke initiation. The observation that arimoclomol showed therapeutic benefit even after 48 hours in this embolic model of stroke gives us even more confidence in the drug’s potential in this indication,” added Dr. Barber.

CytRx previously reported positive results from animal permanent stroke studies indicating arimoclomol significantly accelerated the recovery of sensory and motor function in an experimental rat model of stroke, even when treatment was withheld as long as 48 hours after stroke was induced.

About Arimoclomol

Arimoclomol, a molecular chaperone regulator drug candidate, is being considered as a treatment for amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and stroke recovery. Arimoclomol has been studied in seven Phase 1 and two Phase 2 clinical trials without any significant adverse events. CytRx’s Phase 2b clinical trial with arimoclomol as a treatment for ALS was placed on clinical hold by the FDA in January 2008, unrelated to any data generated by human studies, and additional preclinical toxicology studies are underway to resolve this issue. CytRx expects early in the second quarter to submit animal toxicology data to the FDA relating to the arimoclomol clinical hold. Given this timeline, the Company anticipates a response from the FDA in the third quarter.

About Molecular Chaperone Regulation

CytRx is a leader in molecular chaperone regulation technology. The Company currently has two orally administered, clinical-stage, drug candidates and recently discovered a series of additional compounds that may provide a pipeline for additional drug candidates. The Company’s drug candidates are believed to function by regulating a normal cellular protein repair pathway through the activation or inhibition of “molecular chaperones.” Because damaged proteins are thought to play a role in many diseases, activation of molecular chaperones that help to reduce the accumulation of misfolded proteins may have therapeutic efficacy in a broad range of disease states. Similarly, CytRx believes that the inhibition of molecular chaperones that normally help protect cancer cells from toxic misfolded proteins may result in the selective destruction of cancer cells.

About CytRx Corporation

CytRx Corporation is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. The CytRx drug development pipeline includes programs in clinical development for cancer indications, including tamibarotene in a registration study for the treatment of acute promyelocytic leukemia (APL). CytRx is developing two drug candidates based on its industry-leading molecular chaperone technology, which aims to repair or degrade misfolded proteins associated with disease. The Company owns and operates a research and development facility in San Diego. CytRx also maintains a 45% equity interest in publicly traded RXi Pharmaceuticals, Inc. (NASDAQ: RXII). For more information on the Company, visit cytrx.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including risks relating to the predictive power of this or any other animal model of stroke recovery to humans, the outcome or results of any future pre-clinical or clinical testing of arimoclomol for stroke recovery, uncertainties related to the impact of the FDA’s clinical hold on our clinical program for arimoclomol for the treatment of amyotrophic lateral sclerosis on the timing and ability to initiate further clinical development for stroke recovery, the risk that any requirements imposed on our planned clinical trial design for stroke recovery by the FDA as a result of the concerns expressed in their clinical hold of our ALS program might adversely affect our ability to demonstrate that arimoclomol is efficacious in treating stroke patients, risks related to CytRx’s ability to enter into partnerships to advance the clinical development of arimoclomol, risks related to CytRx’s need for additional capital or strategic partnerships to fund its ongoing working capital needs and development efforts, risks related to the future market value of CytRx’s investment in RXi and the liquidity of that investment, and the risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx’s most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Source
CytRx Corporation

Dialysis Patients Half as Likely to be Treated After a Heart Attack

Despite a higher risk of death after a heart attack, dialysis patients are only half as likely to receive standard
treatment after suffering from one, compared to the general population, according to a new study being presented at the
American Society of Nephrology’s 37th Annual Meeting and Scientific Exposition in St. Louis, Missouri.

“The difference between the treatment of dialysis and non-dialysis patients appears to be based primarily on their status as
dialysis patients,” says lead author of the study, David Charytan, MD, a clinical and research Fellow at Brigham and Women’s
Hospital in Boston, Massachusetts. “Physicians seem to be more reluctant to prescribe invasive but potentially life-saving
therapies for dialysis patients than for their other patients.”

The study involved more than 150,000 patients who were admitted with a heart attack in 2001 and examined whether dialysis
patients received less aggressive care for their heart disease than non-dialysis patients. Findings show that dialysis
patients were approximately half as likely to have their coronary arteries studied or coronary blockages repaired.

“In light of these findings, doctors should evaluate their practices and consider more frequent use of angiography, bypass
surgery, and other coronary interventions in dialysis patients,” says Charytan.

Cardiovascular disease is the leading cause of death among patients on dialysis with kidney failure or end stage renal
disease (ESRD) on dialysis. Cardiovascular damage begins as soon as the kidney loses function and increases in severity
during the progression of kidney disease.

The study results will be presented at a news briefing from 12:15 – 1:15 p.m. on Friday, October 29 in Room 251 of the
America’s Center. The study abstract, “Underutilization of Coronary Angiography and Revascularization in Dialysis Patients is
Not Explained by Comorbidity and is Associated with Increased Mortality after Myocardial Infarction” (SA-PO407) will be
presented during a poster session on Saturday, October 30 at 10:00 AM in Exhibit Halls 2-4 of the America’s Center.

The ASN is a not-for-profit organization of 9,000 physicians and scientists dedicated to the study of nephrology and
committed to providing a forum for the promulgation of information regarding the latest research and clinical findings on
kidney diseases. ASN’s Renal Week 2004, the largest nephrology meeting of its kind, will provide a forum for more than 12,000
nephrologists to discuss the latest findings in renal research and engage in educational sessions relating advances in the
care of patients with kidney and related disorders from October 27- November 1, 2004 at the America’s Center in St. Louis,
Missouri.

American Society of Nephrology (ASN)
1725 I St., NW, Ste 500
Washington, DC 20006
United States
Phone 202-416-0658
asn-online

Visipaque Linked To Lower Incidence Of Contrast-Induced Nephropathy And Cardiovascular Events In Chronic Kidney Disease Patients Compared To Iopromide

A first-ever 208-person study comparing the renal safety, occurrence of cardiovascular adverse events and diagnostic image quality of GE Healthcare’s isosmolar contrast media (CM) iodixanol (Visipaque) and the low-osmolar CM iopromide in select patients concluded iodixanol is associated with lower incidence of contrast-induced neuropathy (CIN) and cardiovascular events (CV) than iopromide, when used in patients with chronic kidney disease. The study is published in December’s Catheterization and Cardiovascular Interventions, a leading scientific journal that covers current hot topics in interventional imaging.

The prospective, randomized, double-blind, single-center study was authored by Bin Nie, M.D. and colleagues from Beijing Anzhen Hospital, Beijing, People’s Republic of China. The authors’ objective for the study was to compare the renal safety as well as cardiovascular effects and diagnostic image quality of iso-osmolar iodixanol vs. low-osmolar iopromide in patients with chronic kidney disease (CKD) undergoing coronary interventions.

“Given the increase in patients with CKD and also with heart disease we wanted to investigate if there was a difference in renal and cardiovascular complications between the isosmolar contrast medium iodixanol and the low osmolar contrast medium iopromide,” said Dr. Bin Nie. “These results may have an important influence in clinical decision making regarding the selection of the appropriate contrast media for the appropriate patient.”

The conclusion of the study indicates that isosmolar CM iodixanol appears to be associated with a significantly lower incidence of CIN and composite CV compared with the low-osmolar CM iopromide in patients with CKD undergoing coronary angiography with or without PCI. The authors indicated that there was no difference in image quality between the two contrast media, in spite of iopromide’s higher iodine content.

Prof. Yu-jie Zhou, the correspondence author noted that in the paper that their results are of interest in light of the 2007 AHA/ACC guidelines for the management of patients with Unstable-Angina/Non-ST-Elevation Myocardial Infarction (UA/NSTEMI) and the AHA/ACC/SCAI 2007 Update of the Guidelines for PCI. These guidelines recommend the use of isosmolar contrast in patients with CKD who undergo coronary arteriography.

“This study reinforces why we believe that Visipaque is an appropriate choice for high- risk patients, ” said Eric Cantor, MD, head of medical and professional services for GE Healthcare’s Medical Diagnostics business in the Americas. “The lower incidence of CIN associated with Visipaque seen in this study is consistent with a number of studies that have found lower CIN rate with Visipaque, some several of which reached statistical significance. Those that reach statistical significance have followed the rigorous, multiple standardized post dose serum creatinine measurement design utilized by Dr. Nie and colleagues. Additionally the lower cardiovascular event rates associated with Isosmolar Visipaque seen in this study is consistent with other studies such as the COURT (vs ioxaglate) and VICC (vs iopamidol) studies.”

The authors noted however, that their study did not match with another recent study, likely due to different standards for measuring Serum Creatinine levels (SCr) post-dose. They wrote, “For a given study population, non-standardized measurement of post-procedure SCr at one random time point may not accurately reflect the true incidence of CIN, as different CM may exert their maximal effect on the kidney at different time points after administration in different individuals1,2. The critical role of standardized timing in post-procedure SCr measurement is illustrated by our findings that on day 2 after CM administration peak SCr levels were observed in 90 and 82% of patients who received iodixanol and iopromide, respectively, whereas on day 3 the corresponding peak SCr increases occurred in 10 and 18% of patients.”

About Visipaque, Select Safety Information

In the U.S., Visipaque™ (iodixanol) Injection Nonionic Isosmolar VISIPAQUE IS NOT FOR INTRATHECAL USE. All nonionic, iodinated contrast media currently available inhibit blood coagulation, in vitro, less than ionic contrast media. Clotting has been reported when blood remains in contact with syringes containing nonionic contrast media. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and nonionic contrast media. Caution must be exercised in patients with severely impaired renal function, combined renal and hepatic disease, combined renal and cardiac disease, severe thyrotoxicosis, myelomatosis, or anuria, particularly when large doses are administered.

Before administering this product please see the product’s full prescribing information located at gehealthcare. Because indications vary, consult your country-specific prescribing information.

About GE Healthcare

GE Healthcare provides transformational medical technologies and services that are shaping a new age of patient care. Our expertise in medical imaging and information technologies, medical diagnostics, patient monitoring systems, performance improvement, drug discovery, and biopharmaceutical manufacturing technologies is helping clinicians around the world re-imagine new ways to predict, diagnose, inform, treat and monitor disease, so patients can live their lives to the fullest.

GE Healthcare’s broad range of products and services enable healthcare providers to better diagnose and treat cancer, heart disease, neurological diseases and other conditions earlier. Our vision for the future is to enable a new “early health” model of care focused on earlier diagnosis, pre-symptomatic disease detection and disease prevention. Headquartered in the United Kingdom, GE Healthcare is a $17 billion unit of General Electric Company (NYSE: GE). Worldwide, GE Healthcare employs more than 46,000 people committed to serving healthcare professionals and their patients in more than 100 countries. For more information about GE Healthcare, visit our website at gehealthcare.

References

1. Rudnick MR, Goldfarb S, Wexler L, Ludbrook PA, Murphy MJ, Halpern EF, Hill JA, Winniford M, Cohen MB, VanFossen DB. Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: A randomized trial. The iohexol cooperative study. Kidney Int 1995;47:254-261.

2. Davidson CJ, Hlatky M, Morris KG, Pieper K, Skelton TN, Schwab SJ, Bashore TM. Cardiovascular and renal toxicity of a nonionic radiographic contrast agent after cardiac catheterization. A prospective trial. Ann Intern Med 1989;110:119-124.

3. Davidson CJ. Laskey WK, Hermiller JB, Harrison JK, Matthai W, Vliestra RE, Brinker JA, Kereiakes DJ, Muhlestein JB, Lansky A, Popma JJ, Buchbinder M, Hirschfield JW. Randomized trial of contrast media utilization in high-risk PTCA (The COURT Trial). Circulation 2000; 101: 2172 – 2177.

4. Harrison JK, Hermiller JB, Vetrovec GW, Smith JE, Pulsipher MW, Kern MJ, Conn EH, Navetta, FI, She, L, Pieper K, Sketch zzmh, Tcheng JE, Davidson CJ. A randomized study of 1276 patients undergoing PCI using iodixanol (Visipaque) vs iopamidol (Isovue); comparison of in-hospital and 30 day major adverse cardiac events. The results of the VICC trial. Circulation 2003; 108: S 354 – S 355 (abstract).

GE Healthcare

View drug information on Visipaque.