Flightless I is a novel drug target that regulates important cellular behaviours including mobility, contraction, adhesion, proliferation and cytokine production. The activity of Flightless I is mediated through interaction with components of the cell’s cytoskeleton, modulation of intracellular signalling pathways and regulation of cellular transcription events.
The flightless I gene was originally identified in Drosophila melanogaster, where mutations in the flightless I locus were found to cause flightlessness due to disordered indirect flight muscles (Campbell et al., (1993) PNAS 90 11386-11390).
Flightless I is a negative regulator of the migratory and proliferative events of tissue repair. Inhibition of Flightless I using antibodies has been shown to improve wound repair in murine and porcine models of normal and compromised would healing [reference publication link], and a murine model of Epidermolysis Bullosa (see figure below) [reference the publication list link].
In addition, anti-flightless antibodies have been shown to reduce the incidence and growth of skin tumours in a mouse model of squamous cell carcinoma (see below).
Treatment of early stage blisters with anti-flightless antibodies improve healing in a mouse model of Epidermolysis Bullosa
Reference: Kopecki et al., 2012 Topically Applied Flightless I Neutralizing Antibodies Improve Healing of Blistered Skin in a Murine Model of Epidermolysis Bullosa Acquisita J Invest Dermatol 133:1008-16
Anti-flightless antibodies formulated in a cream vehicle were applied onto the skin of EB mice for three consecutive days at the start of blister formation. EB mice treated with anti-flightless antibodies were observed to have significantly fewer blisters and reduced number of lesions compared with EB mice treated with control IgG antibody.
Treatment of skin tumours with anti-flightless I reduces their incidence and severity.
Reference: Kopecki Z, Yang GN, Jackson, JE, Melville E, Caley MP, Murrell DF, Darby I, O’Toole EA, Samuel MS Cowin AJ. (2015) Cytoskeletal protein Flightless I inhibits apoptosis, enhances tumor cell invasion and promotes cutaneous squamous cell carcinoma progression Oncotarget Nov 3;6(34):36426-40.
Therapeutic antibodies for regenerative medicine.
AbRegen is a preclinical stage biotechnology company that specialises in the development of antibody-based therapeutics for tissue repair applications.