Fibrosis is defined as an excessive accumulation of extracellular matrix. It can affect many organs, including the lungs, liver, heart, skin, kidneys and muscles. Muscle fibrosis is the result of a defective regeneration process, unresolved inflammation or chronic damage.
Many muscle diseases have a combination of high levels of fibrosis and muscle wasting and weakness. This phenomenon, which alters muscle homeostasis, regeneration and the environment in which the muscle fibres reside, can interfere with gene and cell therapies. Therefore, slowing down or even reversing fibrosis is an essential therapeutic goal to maintain muscle identity so that therapies remain effective.
In this review published in December 2022, researchers from the “Cell and Molecular Orchestration in Muscle Regeneration, Aging and Disease” team at the Myology Centre for Research present an updated overview of drug therapies that have been tested to reduce fibrosis in skeletal muscle. The multifactorial causes of fibrosis and the numerous cell types potentially involved make it a complex process to target. However, many pharmacological agents have been tested in preclinical and clinical trials showing that targeting fibrosis can improve muscle function. Targets include TGFβ, connective tissue growth factor (CTGF), matrix metalloproteinases (MMPs), the renin-angiotensin system (RAS), oxidative stress and inflammation.
