Discovering significant breakthroughs in fibrosis.
Blade will initiate clinical trials in human fibrotic disease in the coming months.
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Diseases characterized by uncontrolled, progressive fibrosis include non-alcoholic steatohepatitis (NASH), idiopathic pulmonary fibrosis (IPF), primary sclerosing cholangitis (PSC), systemic sclerosis (SSc) .
Non-Alcoholic Steatohepatitis (NASH)
It is estimated that up to one-third of the populations in the US and Europe have a condition termed non-alcoholic fatty liver disease (NAFLD), which is characterized by steatosis, or excessive accumulation of fat in the liver (Wree, 2013; Blachier, 2013). Many of these individuals, for reasons not totally understood, subsequently develop liver inflammation, or steatohepatitis. This condition, called non-alcoholic steatohepatitis, or NASH, develops in roughly 10 - 20% of NAFLD patients, accounting for approximately 10 - 20 million individuals in the US (Schattenburg, 2011). Individuals experiencing chronic liver inflammation often develop liver fibrosis, with eventual risks of cirrhosis, hepatocellular carcinoma, and liver failure. Based on current projections, NASH is predicted to become the leading cause of liver transplantation by 2020 (Wree, 2013). Unfortunately, there are no therapies available to prevent or treat liver fibrosis.
Idiopathic Pulmonary Fibrosis (IPF)
Idiopathic pulmonary fibrosis (IPF) is a rare, highly debilitating, and poorly understood disease. Most commonly affecting individuals over 50 years old, IPF is characterized by interstitial pneumonia and chronic progressive lung fibrosis. Over the course of the disease, healthy lung tissue is replaced with fibrotic tissue, causing a continuous decline in lung function. Disease progression is unpredictable and is often rapid, with many patients progressing to lung failure and potentially death within 2 - 3 years. Unfortunately, the disease’s early genesis is unknown, and there are no tests to identify patients that are at greatest risk of developing IPF. Members of Blade’s own team were instrumental in the pioneering work at InterMune that led to the approval of pirfenidone to treat IPF; however, there remains a pressing need for effective therapies for this serious and as-of-yet incurable disease.
Primary Sclerosing Cholangitis (PSC)
Primary sclerosing cholangitis (PSC) is a rare, chronic, progressive disease characterized by inflammation and subsequent destruction of intra- and extrahepatic bile ducts. Over time, patients develop liver fibrosis and cirrhosis, which ultimately can lead to liver failure. PSC is also associated with increased rates of colorectal, hepatobiliary, and gallbladder cancer (Kumar, 2016). Epidemiology studies indicate that there may be up to 50,000 individuals afflicted with PSC in the US (Ali, 2015), although prevalence rates are generally presumed to be underestimated due to the difficulty of correctly diagnosing asymptomatic patients (Eksteen, 2014). Disease management primarily entails symptomatic treatment (for example, of pruritus and fatigue), but there are no FDA-approved agents to treat PSC, and no therapies have been shown to consistently slow disease progression. An anti-fibrotic agent that effectively delays disease progression would be of tremendous benefit to individuals with PSC.
Systemic Sclerosis (SSc)
Systemic sclerosis (SSc), or scleroderma (which translates to hardening of the skin), is a rare, chronic autoimmune disease characterized by fibrotic and vascular abnormalities. Most individuals with SSc exhibit some degree of skin fibrosis, although many patients also progress to develop fibrosis within internal organs, potentially leading to severe complications and organ failure. Disease progression is highly variable in SSc, with some patients remaining stable for years and others developing severe complications relatively rapidly. The underlying biology in SSc is complicated and poorly understood, which has hampered efforts to develop effective and curative therapies. Disease management is predominantly through patient-specific symptomatic interventions and systemic immunosuppression, neither of which are curative. An effective anti-fibrotic therapy could prolong organ function and offer tremendous benefit for SSc patients.
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