TherapeuticAdvance-June 2005

Welcome to the June edition of TherapeuticAdvances, LeadDiscovery's free newsletter for the drug development sector. Read on for editorial comment on selected studies recently featured on DailyUpdates our regular bulletin of breaking journal articles and drug development news

Featured on DailyUpdates-CNS Disorders

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Todays highlighted journal article from DailyUpdates-Oncology
Epigenetic modulation of retinoic acid receptor beta2 by the histone deacetylase inhibitor MS-275 in human renal cell carcinoma. Clin Cancer Res. 2005 May 1;11(9):3535-42.

Todays lead news item from DailyUpdates-Immunology & Inflammatory Disease
REMICADE Granted Priority Review by U.S. Food and Drug Administration for Treatment of Ulcerative Colitis; First Biologic to Show Efficacy in Phase III Trials for Ulcerative Colitis

Recent PharmaReports from LeadDiscovery
A full list of reports can be found arranged into therapeutic area at LeadDiscovery's PharmaReport center or through our search engine at the center. The list below gives the most recent additions

• Histone deacetylase inhibitors-Moving from the bench to a promising companion for classic and targeted cancer therapies
• Endocrinology 2005
• Pipeline Insight: HIV Therapeutics
• Emerging Drug Discovery Technologies: Building competitive advantage through lab-on-a-chip, nanotechnology and RNAi
• Acute Stroke - Symptom Awareness Will Reduce Headache
• Pipeline Insight: Hematological malignancies-Targeted treatments and immunotherapy infuse new blood
• Pipeline Insight - Hepatitis B therapeutics
• Genomics World Markets
• Pipeline Insight: Asthma, COPD and Allergic Rhinitis Therapeutics
• Pipeline Insight: Hepatitis C
• Innovative Cancer Therapies: Targeted therapy, a clinical and commercial revolution
• Cancer Vaccines and Cell Therapies
• Breast Cancer - Changing Treatment Paradigms for Local and Locally Advanced Breast Cancer
• Monoclonal Antibody Therapies
• Cancer Vaccines and Cell Therapies

Featured on DailyUpdates-Oncology

Focus on Metabolic Diseases:
Vanilloid receptor desensitization as a strategy for improving glucose tolerance as well as reducing diabetic neuropathic pain The vanilloid capsaicin has long been known to desensitize pain pathways leading to long-term analgesia through selectively binding to small unmyelinated sensory afferent nerves. However the pungency and systemic toxicity of capsaicin has largely precluded its therapeutic utility. Recent data published by Dorte X. Gram from Novo Nordisk A/S are now emerging to suggest that sensory afferents might also be implicated in the development of glucose intolerance. The present study reports that sensory nerve desensitization by resiniferatoxin, a capsaicin analogue with reduced relative pungency compared to capsaicin is able to improve glucose tolerance, increase glucose-induced insulin release and inhibit DPPIV (dipeptidyl peptidase IV) activity. Hence, either resiniferatoxin, its synthetic analogues or other compounds that can downregulate sensory nerve activity could offer a novel approach to metabolic control as well as neuropathic pain that develops in response to prolonged metabolic imbalance...[more]

Featured on DailyUpdates-Metabolic Disorders

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Focus on Immunology, Inflammation & Infectious disease:
Viramidine (Valeant Pharmaceuticals), a ribavirin prodrug for the improved treatment of hepatitis C (HCV) infection: reduced anemia with similar efficacy compared to ribavirin Hepatitis C virus (HCV) infection produces cirrhosis, end-stage liver disease and liver cancer and by 2010 38,000 deaths will result from infection. The current standard of care for chronic HCV infection is a combination of an interferon-alpha product and ribavirin however under-use of available treatments as well as anemia associated with ribavirin represents a serious problem (for further information see our feature "Pipeline Insight: Hepatitis C"). Even so, worldwide sales of ribavirin totalled approximately $1.2 billion in 2002. Opportunities for prodrugs of ribavirin are immense both in terms of patient care and pharmaceutical revenue. Valeant have developed a prodrug of ribavirin, viramidine which is activated within the liver resulting in reduced levels of ribavirin accumulating in red blood cells. The present phase I study of viramidine demonstrates the excellent absorption and activation of oral viramidine. Although treatment with viramidine resulted in the accumulation of ribavirin in the plasma and red blood cells viramidine displayed good tolerability and infrequent hemolysis. Since a phase II study has been successfully completed demonstrating reduced anemia but equal efficacy with viramidine compared to ribavirin and phase III studies have now been initiated...[more]

Featured on DailyUpdates-Infectious Diseases

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Focus on Angiogenesis:
Combining Avastin and Tarceva as a synergistic approach to cancer? Lung cancer is the most common cancer worldwide with 1.2 million new cases diagnosed annually. The development of Avastin (bevacizumab) and Tarceva are promising to improve this situation as well as offering hope to other patients with diverse cancers (see Innovative Agents in Lung and Colorectal Cancer). Researchers conducting a phase I/II study now report that the combination of Avastin and Tarceva may be of benefit to patients with advanced non-small cell lung cancer (NSCLC) as well as with other solid tumors...[more]

Featured on DailyUpdates-Infectious Oncology

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Focus on Airway Disease:
Improved assay technology for the evaluation of airway therapeutic activity or toxicology Assaying therapeutic agents requires the availability of apparatus to dose experimental animals as well as to measure biological effect. Available dosing systems for inhalation agents are suboptimal generally causing stress to the animal as well as exposing the operator to potentially harmful agents. based researchers have developed apparatus that allows mice to be dosed with reproducible levels of test substance under medium-throughput and low stress conditions. The system can be used to assay efficacy of airway therapeutics (including small molecules and gene therapies) and agents designed for airway delivery. This dosing chamber system can also be used to safely evaluate the respiratory tract toxicology of test substances....[more]

Featured on DailyUpdates-Immunology & Inflammatory Diseases

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Focus on CardioVascular disease:

Renalase as a new target for the treatment of cardiovascular disease particularly amongst patient with end-stage renal diseaseThe antihypertensive market was valued at $31 billion in 2003. Although the development of generic equivalents has reduced the market value of the four major antihypertensive classes, the angiotensin II receptor blocker class has experienced strong growth (see Antihypertensives - Together We Stand, Divided We Fail). The kidney plays an important role in regulating blood pressure and the renal enzyme renin is a target for what is expected to be the next blockbuster class of anti-hypertensives. The report highlighted here identifies a further renal enzyme, renalase that may be another target for the treatment of hypertension. Renalase may be particularly important in the increasingly problematic group of patients with end-stage renal disease...[more]

Featured on DailyUpdates-Cardiovascular Diseases

Focus on CNS Disease:

Taishi's 20-HETE synthesis inhibitor, TS-011 as a candidate acute treatment for hemorrhagic and ishemic stroke: Each year, 750,000 strokes occur in the US and resultant deaths account for stroke being one of the top three causes of mortality as well as a major economic burden on healthcare systems (see Acute Stroke - Symptom Awareness Will Reduce Headache). Most strokes are ischemic however 20% are hemorrhagic; irrespective of the subtype treatments are limited. One candidate molecular target for stroke is 20-HETE, an ecosanoid that has been suggested to contribute to the development of vasospasm. Taisho Pharmaceutical have developed a potent and selective 20-HETE synthesis inhibitor, TS-011 which has been reported to display efficacy in models of both hemorrhagic and ischemic stroke. The latest available new from Taisho is that TS-011 entered phase I development in the US in 2003...[more]

Featured on DailyUpdates-CNS Diseases

Focus on Cell Death:
Development stage candidate from Bayer Healthcare for the treatment of traumatic head injury, stroke, Parkinson's disease and Alzheimer' s disease Acute neurodegeneration caused by stroke or trauma as well as more chronic disease resulting from Alzheimers’s disease or Parkinson’s disease has inflammatory and direct neurotoxic components. There is an urgent need for improved neuroprotective agents driving the development of a market expected to be worth $11.5 billion by the year 2010 (see Neuroprotection - Drugs, Markets and Companies). The transcription factors, NF-Kappa B and AP-1 are though to play an important role in both the transcription of inflammatory mediators and cell survival. Bayer Healthcare researchers have developed synthetic derivatives of the phytogenic therapeutic, Rocaglaol. The lead compound is shown here to have broad ranging anti-inflammatory and neuroprotective active resulting is therapeutic activity in models of head injury and Parkinson’s disease....[more]

Featured on DailyUpdates-CNS Diseases

Focus on Pain:
A-425619: A TRPV1 receptor antagonist with potential for the treatment of inflammatory, postoperative and arthritic pain The worldwide analgesic market was worth $38 billion during the year 2002 and is expected to nearly double to $75 billion by the year 2010 (for a recent and in depth insight see Pain Therapeutics - Drugs, Markets and Companies). The vanilloid receptor TRPV1 (VR1) has now become an attractive molecular target for multiple sub-types of pain. Abbott researchers have recently described the development of A-425619, a low nanomolar TRPV1 antagonist. This molecule blocks heat hypersensitivity in a model of inflammatory pain as well as posoperative and arthritic algesia. Although A-425619 was demonstrated to have considerable potential as an anti-hyperalgesic agent and effect on neuropathic pain was not observed...[more]

Featured on DailyUpdates-CNS Diseases