We expect that this project will ultimately generate a muscle-on-chip that reproduces the architecture and contractility of in vivo skeletal muscle. The applications of such a chip are numerous and diverse. Nevertheless, our primary target is to provide an in vitro tool for biological and drug studies in the realm of muscle disorders, aging and neuromuscular diseases.
Skeletal muscle disorders pose a significant socioeconomic burden since patients quickly become dependent with reduced or no mobility. Costs of illness are estimated to approximately €1 billion/year in the US, whereas funds allocated to muscular dystrophy research amount to €150 million/year by NIH alone (excluding clinical trials). Although certain drugs recently approved by FDA appear to slow down the progression of dystrophies in a subset of affected individuals, these are certainly not providing a cure for the disease itself.
Natural loss of muscle mass is of particular concern as aged individuals spiral down a negative feedback loop of decreased muscle mass and physical activity. Sarcopenia is the natural atrophy of skeletal muscle during old age. Sarcopenia is linked with the development of obesity, osteoporosis and diabetes type II all of which are highly prevalent in the elderly. Together these diseases increase risk of falling, hospitalization, institutionalization and ambulatory care which has a strong psychological impact on affected individuals and an important economic burden for society. Alone, sarcopenia costs were estimated at 18.5$ billion per year in the US in 2004 and it increases hospitalization costs of other disorders by 58.5%. These numbers will all be inflated by the growing aging population. It is estimated that by 2050 the world’s population above 60 year’s old will double reaching around 2 billion world-wide. This generalized aging poses a series of challenges for society being a burden for increasingly dependent individuals and for our healthcare system.
This project will provide a human system mimicking in vivo conditions in which all properties of muscles can be monitored (contractility, force generation, hypertrophy, structure) and different drug delivery methods can be applied (direct or intravenous). More importantly, this system will arise from hIPSCs and can therefore recapitulate specific patient mutations, which are the main cause of muscle disorders. This 3D muscle system is destined to feed most sectors of the muscle healthcare industry: drug screening, genetic and regenerative therapies, muscle building and prosthetics.
The short term impact of the project will be reflected in:
- new tools for biological investigation, especially in the field of muscle and neuromuscular junction regeneration and maintenance.
- greater accuracy of drug screening and validation thereby reducing time and costs.
- reduction of animal use for drug testing.
- increased interest of the pharmaceutical industry for muscle disorders.
The long term impact of our project includes:
- reducing the 'time to market' for drugs.
- novel drugs and other treatments for (neuro)muscular diseases.
- the foundation for other bioengineered tubular organ systems.
- modelling muscle function for optimal strength performance.
