In Duchenne, cycles of tissue injury with incomplete repair result in muscle fibre loss. The muscle fibres are replaced by fibrotic scar tissue. Fibrosis is a major contributor to muscle weakness and so there is a need to develop therapies to reduce fibrosis in muscle.

Transforming growth factor-beta (TGFβ) has emerged as a therapeutic target because of its importance in the biological process that causes fibrosis. Many potential anti-fibrotic therapies that inhibit the TGFβ pathway have been tested in animal models for Duchenne.

One of these drugs, HT-100, is being tested in a phase I/II clinical trial sponsored by Akashi Therapeutics. This study is currently suspended for recruitment while a potential safety issue is investigated.

Other TGFβ inhibitors, including pirfenidone, suramin and imatinib have shown some anti-fibrotic activity in mouse models of Duchenne but are not under active clinical development at this time.

MicroRNAs (miRNAs) are a class of small, naturally occurring noncoding RNA molecule that regulate gene expression. Several hundred mammalian miRNAs have been identified, many of which are tissue-specific. Growing evidence suggests that miRNAs are involved in the fibrotic process in many organs including heart, liver, kidney and lungs.

Reduced expression of miR-29 has been linked to muscle tissue in people with Duchenne and ways of overcoming the reduced expression are being investigated as a potential therapy for the future.

Published on 3 March 2016

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