Oxidative metabolism and atrophy in primary human skeletal muscle cell
Research type
Research Study
Full title
Primary culture of human skeletal muscle cells from patients with conditions impairing muscle mitochondrial oxidative metabolism and causing muscle atrophy to investigate underlying molecular mechanisms of reduced oxidative metabolism and atrophy and potential novel therapies
IRAS ID
214624
Contact name
Samantha Amanda Natanek
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Patients with medical conditions who become chronically physically inactive develop leg muscles with a reduced ability to utilise oxygen to generate energy efficiently during exercise and muscle wasting. This occurs in patients with Chronic Obstructive Pulmonary Disease, cardiac failure, type 2 diabetes mellitus (T2D), obesity, and renal failure for example. Loss of leg muscle aerobic capacity results in the muscle becoming energy-depleted prematurely during exercise, and wasting causes muscle weakness, hence the muscle fatigues prematurely. This muscle fatigue limits patient ability to exercise, but also correlates with high blood sugar levels in diabetics and weight gain over time in obese people. The only current treatment that increases muscle aerobic capacity and bulk is an exercise program, and when these improve, there is a proportionate increase in exercise capacity and blood sugar levels. However, not all patients will or can complete an exercise course and a significant proportion of patients do not derive a significant objective health benefit from an exercise course. Therefore if we knew which molecular mechanisms control muscle oxidative metabolism and bulk, we could develop medications that increase these to be used alongside exercise. To investigate mechanisms controlling muscle oxidative metabolism and bulk we often use mouse or healthy human muscle cell lines grown in a Petri dish, as an alternative to giving untested treatments to patients which is not ethical. However mouse and healthy human cell lines may not respond the same way as muscle within patients. Therefore, we would like to take muscle biopsies from patients (a well-validated clinical and research technique) and keep these cells in culture to test mechanisms regulating oxidative metabolism and bulk within them, as we believe this is the best cell equivalent to model the behaviour of muscle cells within a patient.
REC name
London - Fulham Research Ethics Committee
REC reference
17/LO/0300
Date of REC Opinion
28 Mar 2017
REC opinion
Further Information Favourable Opinion