GNETs
Gastric neuroendocrine tumours (GNETs) are extremely rare, affecting 0.0032% of the European population (M. Boyce, 2015). A large number of these cases are due to hypergastrinaemia, a condition characterised by high levels of gastrin production. Gastrin is a hormone that acts on ECL cells in the stomach, causing them to produce histamine as part of the acid-production pathway. Over-production of gastrin causes the formation of neuroendocrine tumours. Netazepide is a gastrin receptor antagonist and shows promise in treating this rare disease.
Chronic Heart Failure
Chronic heart failure affects about 900,000 people in the UK and has an extremely poor prognosis, with a mortality of 30−40 % in the first year (NICE 2010, Chronic heart failure in adults: management). Chronic heart failure is a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the heart to function as a pump to support physiological circulation. Pre-clinical data suggests that TR4 may mediate therapeutic effects in patients with chronic heart failure.
Asthma
Asthma is a respiratory condition that affects 5.4 million people in the UK (Asthma UK, 2016). Asthma is characterised by airway hyper-responsiveness and airway inflammation. As a long-term medical condition, it is important to safely manage asthma symptoms. The mainstay treatments for asthma are reliever and preventer inhalers. However, these can become less effective over time. Pre-clinical data demonstrates that long-term treatment with TR4 may maintain the therapeutic effects of inhalers in asthmatics.
Takotsubo Cardiomyopathy
Takotsubo cardiomyopathy, which is also known as ‘broken-heart’ syndrome, was first described in 1990 in Japan (Sato et al 1990; Dote et al 1991), but has since been recognised in many other countries. Takotsubo cardiomyopathy is a severe form of heart failure. The main symptoms are acute chest pain and dyspnoea and the initial presentation is easily confused with that of acute coronary syndrome or acute myocardial infarction. Takotsubo cardiomyopathy is considered a rare condition; only 1–2% of patients with symptoms suggestive of acute myocardial syndrome are eventually diagnosed as Takotsubo cardiomyopathy. Pre-clinical data suggests that TR4 may mediate therapeutic effects in patients with Takotsubo cardiomyopathy.
Inflammatory Diseases
Chronic inflammatory diseases constitute a major health and economic burden. Unfortunately, the benefits of the most potent anti-inflammatory drugs, glucocorticoids (GCs), are offset by poor tolerability. In particular, long-term GC use is associated with a broad spectrum of adverse effects, including weight gain, osteoporosis, diabetes mellitus, hypertension and bacterial infections. The lack of therapeutic approaches that replicate the beneficial effects of GCs, but not their adverse effects, is a major unmet medical need. Data obtained from non-clinical studies indicate that TR8 may mediate therapeutic effects in patients with chronic inflammatory diseases without these adverse effects.