Licensing status

Publication and contact information

Autoimmune disease


Toll-like receptor 4 (TLR4); fibronectin extra domain A (FnEDA)

In vitro and mouse studies suggest inhibiting TLR4 signaling in skin lesions could help treat scleroderma. In samples from skin lesions and sera from patients with scleroderma and in mouse models of cutaneous fibrosis, compared with healthy controls, the TLR4 ligand FnEDA was upregulated. In a mouse model of drug-induced cutaneous fibrosis, knockout of Fneda or subcutaneous treatment with a small molecule TLR4 inhibitor prevented fibrosis and dermal thickening. In mice with established disease, the inhibitor reversed cutaneous fibrosis. Next steps include identifying new TLR4 inhibitors for scleroderma.
At least three companies have TLR4 antagonists in Phase II or earlier testing for autoimmune and other indications.
In addition, Eisai Co. Ltd.'s Eritoran (E5564), a synthetic lipid A analog that blocks TLR4 activation, failed to meet the primary endpoint of reduced mortality in Phase III testing for sepsis, and development is on hold.

SciBX 7(19); doi:10.1038/scibx.2014.550
Published online May 15, 2014

Patent application pending covering the use of new TLR4 inhibitors in scleroderma; BioLineRx Ltd. has an exclusive licensing option

Bhattacharyya, S. et al. Sci. Transl. Med.; published online April 16, 2014;
Contact: Swati Bhattacharyya, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Contact: John Varga, same affiliation as above