Biomarin advance novel antihypertensive...Researchers identify novel molecular target for the treatment of sepsis

Todays Headlines from across the DailyUpdates network (July 7th, 2006) - In today's edition we highlight Biomarin's development of the novel antihypertensive 6R-BH4 and new research describing a promising molecular target for future sepsis therapeutics. Summaries of this content can be seen below or click here for today's edition of DailyUpdates

• Breaking News (from DailyUpdates-Cardiovascular Diseases): Biomarin advance novel antihypertensive: Effective blood pressure control for all hypertensive patients remains an elusive goal. The development trend is currently towards optimizing fixed dose combination therapy rather than the development of single pill alternatives. Rasilez bucks this trend and is set to be the first oral renin inhibitor when it enters the market; it is likely to become a blockbuster by 2010 (see Pipeline Insight: Antihypertensives). The submission for rasilez was accepted for US regulatory review in April 2006; submission for EU approval remains planned for 2006. Today we highlight news from BioMarin who are developing another clinical stage antihypertensive. The company have announced that the first patient has initiated treatment in the Phase 2 clinical study of 6R-BH4 for the treatment of poorly controlled hypertension. The company expects to announce data from this study in early 2007. 6R-BH4 is commonly known as tetrahydrobiopterin, an essential enzyme cofactor that plays a key role in the production of nitric oxide, a molecule that regulates vascular tone. A secondary deficiency of 6R-BH4 disrupts NO production, resulting in loss of vasodilation control and increased blood pressure. Earlier pilot studies have demonstrated that oral administration of 6R-BH4 can reduce blood pressure in individuals who remain hypertensive despite treatment with other medications. 6R-BH4 is the same enzyme cofactor currently being evaluated in BioMarin's Phenoptinfor phenylketonuria. [Source:BioMarin]

Featured Journal Article (from DailyUpdates-Infectious Diseases): Researchers identify novel molecular target for the treatment of sepsis: Sepsis, a complex and rapidly progressing disease with high levels of mortality, presents major challenges with regard to its epidemiology, definition and management. Rising disease incidence has been fuelled by the growing number of surgical interventions and an increase in immunocompromization. Disease management is predominantly non-specific. Recent development has produced only one sepsis-specific drug, Eli Lilly's Xigris. However, according to the analysts Datamonitor, due to the drug's high price point, the narrow label and its contraindications, Xigris has failed to meet expectations, with global 2005 sales totaling $214.6m (see our feature on Sepsis). Takeda's TAK-242, a TLR-4 modulator, is currently in phase 3 development. Today’s featured journal article takes another approach evaluating host modulators of susceptibility to sepsis. The study reports that nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key modifier gene who’s expression plays a major suppressive role on the response to sepsis. Dramatically, within 40 hours following cecal ligation and puncture all mice engineered so that they did not express Nrf2 had died. In stark contrast only 20% of control mice had died. This regulatory process appears to involve the regulation of cellular glutathione and other antioxidants and intriguingly this pathway declines with age. These data suggest that Nrf2 may play a role in the increased risk of death in elderly patients with sepsis as compared to younger patients and suggest that agents able to stimulate Nrf2 expression may be therapeutically useful [[J Clin Invest. 2006 May;116(5):1317-26J Clin Invest. 2006 Apr;116(4):984-95]