TGF-beta superfamily signalling in muscle weakness in PAH
Research type
Research Study
Full title
The role of transforming growth factor beta signalling in the development of muscle weakness in patients with pulmonary arterial hypertension.
IRAS ID
117309
Contact name
S Wort
Contact email
Research summary
Pulmonary arterial hypertension (PAH) is a disease that causes raised blood pressure in blood vessels that pick up oxygen from the lungs. idiopathic pulmonary arterial hypertension (IPAH) a subgroup of these patinets have a life expectancy similar to some cancers. There is treatment available but there is no cure. We now know that IPAH is associated with weakness in the muscles in the legs, which contributes to the symptoms patients’ experience. Researchers believe that certain proteins found in high levels in the blood of patients with other chronic diseases can affect muscle function and growth. One of these proteins is called growth differentiating factor (GDF) 8, high levels of which are associated with muscle weakness in COPD and heart failure (HF). Interestingly there are drugs available which block the actions of GDF-8 on muscle cells which has been shown in animals to result in increased muscle size. A related protein called GDF-15 is found in elevated levels in patients IPAH, and is linked to prognosis. Our preliminary data suggests that GDF-15 can also directly influence muscle size in a number of situations. We aim to investigate the role of GDF-15 and related molecules in the development of muscle weakness in patients with PAH. We will do this by measuring certain markers of muscle weakness and taking blood and muscle samples in patients and controls. We will then compare the levels of GDF-15 in these tissues in those with and without muscle wasting. We hope this work will lead to a greater understanding of the role of GDF-15 in the development of muscle weakness in patients with IPAH. GDF-15 levels may be important in allowing us to define which patients have muscle weakness. In the future we aim to perform a clinical trial of drugs which block the actions of GDF-15.
REC name
London - Camberwell St Giles Research Ethics Committee
REC reference
13/LO/0481
Date of REC Opinion
31 May 2013
REC opinion
Further Information Favourable Opinion