‘JUPITER’ and the risk of heart disease

Statins are blockbuster drugs taken by millions around the world. Results from the ‘JUPITER’ clinical trial[1] indicate that these cholesterol-lowering agents could decrease the risk of heart disease even for persons with low cholesterol levels; meaning that millions more could benefit from popping a statin pill…

But could they really? What indicators and risk factors dictate the prescription of statins? How should vascular risk be measured? And what are the factors that count towards this risk? An Editorial in the January 2009 issue of CMRO discusses the JUPITER study and explores these interesting themes.

The trial suggests that hsCRP, a protein associated with inflammation, can be used to identify subjects without vascular disease who should receive statins despite a low or intermediate calculated risk. The CMRO editorial highlights the fact that risk assessment needs to be re-examined, and discusses the role of hsCRP-testing in what the authors call risk stratification. The authors also feel that guidelines (and clinical practice) may need changing if indeed statins do have a much wider role in preventing vascular disease than was previously thought.

Of course, if relatively healthy persons (‘low or intermediate risk’) are to be prescribed statins, then there are terrific cost implications too. The authors of the editorial remark that this is all the more so if the benefits observed from taking Crestor (used in the JUPITER trial) can not be reproduced by cheaper, generic statins.

At the heart of the ongoing scientific debate, the fundamental question remains: do statins have a convincing role in primary prevention of heart disease? Read the editorial (an open access article) here find out what the authors think.

[1] JUPITER: Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin

Impact of predictive pharmacokinetics

The implementation of studies aiming at predicting ADME properties at preclinical drug discovery stages has been central in the effort to reduce attrition rates.
In a clear and authoritative article reviewing the development, over the past three decades, of Discovery Metabolism and Pharmacokinetics research, Dr Summerfield analyses the key elements which moved the field forward and anticipates how new paradigms, such as translational medicine and systems thinking, will push it further.
He concludes that, although the predictive metabolism and pharmacokinetics approach already proved successful, a strong impact on drug pipelines will only be achieved when pharmacodynamics and toxicology are integrated in a similar way to drug discovery programmes.
The article will be available in the March issue of Expert Opinion on Drug Discovery

Challenges facing liposome-based targeted delivery of antithrombotic drugs

Haemorrhage is a major risk factor associated with administration of thrombolytic protein drugs. In vivo stability with conventional parenteral administration also remains a concern due to the intrinsic nature of thrombolytic protein drugs. Liposome-based delivery systems have been applied to other drugs in order to reduce toxicity, increase site specific action and protect against protein denaturation, but does the same apply to thrombolytic protein drugs and to what extent? Can liposome-based thrombolytic preparations reap the full benefits of this delivery system?

In the review article entitled “Liposomes for targeted delivery of antithrombotic drugs” Elbayoumi & Torchilin review the major work to date on liposome-based delivery of antithrombotic drugs to vascular pathology sites and provide their own perspective on the future of the field.

Will genomic technologies change the landscape of toxicology research?

With so many drug failures due to toxicity concerns, the development of more effective approaches to toxicity testing is of utmost importance. In their recent review “Systems biology and functional genomics approaches for the identification of cellular responses to drug toxicity,” Rusyn and Hege Harrill put forward the view that systems toxicology ‘offers the promise of more accurate predictions of adverse health effects in humans.’ They conclude that ‘Translational research bridging rodent and human toxicity will be the key to the success of this field.’ What will the impact of such approaches be on current gold standard? How widely used will they become?

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CXCR4 antogonists

Several CCR5 antagonists, which inhibit the entry of HIV-1 in the host cell, have proven a valuable strategy for the treatment of AIDS. However, the virus can switch to the CXCR4 co-receptor to enter cells, thus prompting the need for CXCR4 antagonists.
In a review published in the January issue of Expert Opinion on Therapeutic Patents, Dr Liotta explores the preclinical development of such compounds, and finds that this relatively recent field could offer therapeutic options in several disease areas.

Profile: Dimitri Mikhailidis

It seems appropriate that our first profile for the Informa Pharmaceutical Science blog should feature Dr. Dimitri P. Mikhailidis. Dimitri is currently Editor-In-Chief of four journals published by Informa Pharmaceutical Science: Expert Opinion on Investigational Drugs, Expert Opinion on Therapeutic Targets, Expert Opinion on Pharmacotherapy, and Current Medical Research and Opinion. Beyond Dimitri's editorial role, he has been an author on numerous original research articles, reviews, and editorials, with over 60 published articles in Expert Opinion and CMRO since 2000. Lest we give the impression that Dimitri favours our journals over others click here to see his 600+ Pubmed listings.

Dimitri is currently the Academic Head & Honorary Consultant to the Department of Clinical Biochemistry at the Royal Free University College Medical School, University College London, and he holds Visiting Professor positions at Robert Gordon University (Scotland) and University of Ioannina Medical School (Greece). Dimitri has travelled widely to present his research, having lectured in 40 countries around the world. Beyond the editorial posts he holds with the Informa Pharmaceutical Science journals, Dimitri is also Editor-in-Chief of four other medical journals, and holds other editorial positions with several more. And sometimes, apparently, he eats and sleeps, although we have no empirical evidence to support this claim.

Research by Dimitri and his network of collaborators primarily focuses on treatment and prevention of cardiovascular disease, and Dimitri was awarded the British Medical Association (BMA) award for vascular research in 1995. His articles cover a broad spectrum of topics: many are written with an eye towards utility for current clinicians, some cast needed attention on new promising therapies in the drug development pipeline, while still others focus on future directions for research in cardiovascular disease. A notable recent paper published in EOP, authored by Dimitri and his colleague Martin Press from the Royal Free Hospital, reviewed the importance of targeting multiple risk factors, including both traditional and novel cardiometabolic factors, in the prevention of cardiovascular events in patients with type 2 diabetes (available for free download). In another recent publication, an editorial commentary in the March 2008 issue of CMRO, Dimitri and his colleagues present an interesting discussion on how age affects how cholesterol levels can and should be used to predict vascular risk and the implications for elderly patients (available for free download).

Dimitri's most recent article, an editorial in CMRO, is likely to create some waves in the cardiovascular community. The editorial focuses on the growing controversy over the potential danger of abruptly stopping statin use in high-risk patients. Instead of giving away the punchline, read the paper for free here.

How Evolutionary Biology Can Help Design Novel Anti-Viral Drugs

While the concept of evolutionary medicine has been around for well over fifty years, the collaboration between evolutionary biology and medical research has proven less profitable than was predicted by early proponents of the field. However, recent efforts to fight rapidly evolving infectious viral pathogens have been increasingly relying on the underlying understanding of viral evolution in order to design more effective antiviral drugs. Esteban Domingo and his colleagues in a recent perspective for Expert Opinion on Biological Therapy entitled "Future prospects for the treatment of rapidly evolving viral pathogens: insights from evolutionary biology" review the promise of drug design informed by evolutionary biology for overcoming viral escape mutations.

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