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Transparency Life Sciences picked up a win for its bet on open innovation in transforming drug development. The FDA cleared the developer's IND application to study a generic hypertension drug for a new potential use in patients with multiple sclerosis, after the startup tapped crowdsourced input from experts and patients on aspects of the clinical trial.

The study not only used New York-based Transparency's web-based Protocol Builder software to gather ideas on the design of the Phase II effort, but the trial will also be partially virtual. After patients' initial visits to trial sites, the planned 12-month study is expected to use telemonitoring technology from Advanced Monitored Caregiving and other partners to track participants until their final checkups, COO Marc Foster explained to FierceBiotechIT.

With these outside-the-box strategies, Transparency aims to drive down the cost of clinical trials by at least 50%. This is a big goal and one not easily achieved industry-wide, and at first blush, the startup's bold idea might draw some healthy skepticism. As published in a Nature Reviews Drug Discovery article in March, the number of FDA approvals per billion dollars in research money spent has been steadily declining over the past 60 years or so. The authors dubbed this "Eroom's Law," which is Moore's Law spelled backwards. Transparency's Foster believes there is hope for reversing the troubling trend. ... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/3534

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The Multiple Sclerosis Resource Centre

Squiffy's House of Fun - Laughter for Multiple Sclerosis

A study of the ACE inhibitor lisinopril? Alert, alert, Anonymoose!!! You need to follow this.

Both full papers are freely available.

Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity.
Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14948-53.

The renin-angiotensin-aldosterone system (RAAS) is a major regulator of blood pressure. The octapeptide angiotensin II (AII) is proteolytically processed from the decapeptide AI by angiotensin-converting enzyme (ACE), and then acts via angiotensin type 1 and type 2 receptors (AT1R and AT2R). Inhibitors of ACE and antagonists of the AT1R are used in the treatment of hypertension, myocardial infarction, and stroke. We now show that the RAAS also plays a major role in autoimmunity, exemplified by multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Using proteomics, we observed that RAAS is up-regulated in brain lesions of MS. AT1R was induced in myelin-specific CD4+ T cells and monocytes during autoimmune neuroinflammation. Blocking AII production with ACE inhibitors or inhibiting AII signaling with AT1R blockers suppressed autoreactive TH1 and TH17 cells and promoted antigen-specific CD4+FoxP3+ regulatory T cells (Treg cells) with inhibition of the canonical NF-kappaB1 transcription factor complex and activation of the alternative NF-kappaB2 pathway. Treatment with ACE inhibitors induces abundant CD4+FoxP3+ T cells with sufficient potency to reverse paralytic EAE. Modulation of the RAAS with inexpensive, safe pharmaceuticals used by millions worldwide is an attractive therapeutic strategy for application to human autoimmune diseases.

Angiotensin II sustains brain inflammation in mice via TGF-beta.
J Clin Invest. 2010 Aug;120(8):2782-94.

The renin-angiotensin-aldosterone system (RAAS) is a key hormonal system regulating blood pressure. However, expression of RAAS components has recently been detected in immune cells, and the RAAS has been implicated in several mouse models of autoimmune disease. Here, we have identified Ang II as a paracrine mediator, sustaining inflammation in the CNS in the EAE mouse model of MS via TGF-beta. Ang II type 1 receptors (AT1Rs) were found to be primarily expressed in CNS-resident cells during EAE. In vitro, astrocytes and microglia responded to Ang II treatment by inducing TGF-beta expression via a pathway involving the TGF-beta-activating protease thrombospondin-1 (TSP-1). TGF-beta upregulation in astrocytes and microglia during EAE was blocked with candesartan (CA), an inhibitor of AT1R. Treatment of EAE with CA ameliorated paralysis and blunted lymphocyte infiltration into the CNS, outcomes that were also seen with genetic ablation of AT1Ra and treatment with an inhibitor of TSP-1. These data suggest that AT1R antagonists, frequently prescribed as antihypertensives, may be useful to interrupt this proinflammatory, CNS-specific pathway in individuals with MS.

I know! How cool is that?!