Fibrosis is a near final disease stage of virtually all organs and tissues. Fibrotic diseases are responsible for a large proportion of human illness and are estimated to cause almost half of all human deaths in the Western world. Despite huge investments in research, and an increased advances in understanding these fibrotic diseases, there are still no treatments to halt fibrogenesis or reverse established fibrosis.
Fibrosis is observed in atrial fibrillation, atherosclerosis, hypertrophic cardiomyopathy, nonalcoholic steatohepatitis (NASH), diabetic nephropathy, idiopathic pulmonary fibrosis (IPF), inflammatory bowel disease, scleroderma, pancreatic cancer, colon cancer and further.
As a targeted diagnostic imaging company we have decided to focus on pulmonary fibrosis, cardiac fibrosis and hepatic fibrosis. Diseases with a high unmet medical need urging for solutions. In addition, as many solid cancers rely on strong fibrotic stroma we also have included colon cancer in our focus areas.
Cardiovascular disease is responsible for 30% of all deaths and remains the leading cause of mortality worldwide. Ischemic heart disease and endomyocardial fibrosis are the primary causes of end- stage heart failure. The estimated annual costs for cardiovascular disease is over USD700 billion per year, more than any other diagnostic group. There is an urgent need to develop advanced diagnostic tools and improved therapies in the area of cardiac disease and especially cardiac fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a devastating chronic, progressive, fibrosing interstitial lung disease, primarily affecting middle aged and older adults. The exact cause of the disease is not known. The disease is designated as an orphan disease.
The scarring process in the lungs leads to gradual decline of lung function, with the potential for intermittent, unpredictable, acute exacerbations and the development of associated pulmonary hypertension. The disease has high morbidity and mortality rates. Average life expectancy is low and estimated to be only three to five years from diagnosis, with approximately two-thirds of patients dying within five years of diagnosis. Survival rates are comparable to those for some of the deadliest cancers.
Disease diagnosis is primarily based on a typical radiology pattern of usual interstitial pneumonia. This technique is not suitable to diagnose patients with early pulmonary fibrosis or to monitor disease changes in fibrosis activity after therapy.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed countries. NAFLD embraces a pathological spectrum of liver disease, from cases of simple steatosis through steatohepatitis (NASH), to cases with cirrhosis. While NAFLD is highly prevalent (15% – 45%) in modern societies, only 10%-25% of cases develop hepatic fibrosis leading to cirrhosis, end-stage liver disease or hepatocellular carcinoma.
The risk factors and comorbidities for NAFLD and NASH appear to be similar and include obesity, type 2 diabetes, and dyslipidemia. Further, increased age is associated with a worsened disease progression, prognosis and mortality. There is evidence suggesting male sex as a significant risk factor.
NASH generally presents as a silent disease with only minor or no symptoms. In the fatty liver, deposits of fat cause liver enlargement and inflammation. In early stages, patients feel well, but may discover upon routine serological testing that liver enzymes are elevated, thus prompting further examination. However, some patients may experience fatigue, weight loss, and weakness. These symptoms are more common in those who have advanced NASH and liver fibrosis. A patient with cirrhosis will likely experience fluid retention, muscle wasting, bleeding from the intestines, and liver failure.
The first therapeutic approach in NASH and liver fibrosis is to eradicate the underlying causes of the chronic inflammation, as far as possible. Obese patients should normalize their excessive food intake, and HBV and HCV infected patients should be treated with antivirals. Although partial reversal of liver fibrosis is observed in some cases, complete remodeling to cirrhosis can hardly be prevented. There are currently no approved therapies for NASH and liver fibrosis. The only option left in end stage liver disease is liver transplantation, although this is only available for a very limited group of patients.
It is hard to predict which patient will develop fibrosis and who will not. Non-invasive predictive diagnostic tools for early stage fibrosis are currently not present. Ultrasound elastography is used as a special ultrasound technique to test liver stiffness (or elasticity) as a measure of liver fibrosis, but is only useful in established liver fibrosis.
Adenocarcinomas make up 95 percent of all colorectal cancer cases. In the gastrointestinal tract, adenocarcinomas develop in the cells of the lining inside the colon and/or the rectum. They typically start as a growth of tissue called a polyp. A particular type of polyp, called an adenoma, may develop into cancer. Polyps are often removed during a routine colonoscopy before they may develop into cancer.
In the mesenchymal subtype colon epithelial tumors, the PDGF-ß-receptor is typically over-expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGF-ß-receptor expression following epithelial-to-mesenchymal transition, which occurs during metastasis formation.
PDGF-ß-receptor expression in primary colon cancer is correlated with short disease-free and overall poor survival rate and the receptor likely contributes to the aggressive phenotype of colorectal tumors.