Inverse vaccination for auto-immune diseases

Cyclic peptides for the therapy of anti-ß receptor-mediated immune response in chronic congestive heart failure

 

Auto-antibodies have been recognized to cause heart failure in many patients. The antibodies are directed against the beta-adrenergic receptor and mimic the effect of natural ligands, such as epinephrine (adrenaline). This mechanism leads to a chronic over-stimulation of the receptor and consequently, to heart failure – reduced function of the heart. 

Roland Jahns, Valerie Jahns-Boivin and Martin Lohse at the Rudolf-Virchow Centre of the University of Würzburg laid the foundations, on whose basis the team developed cyclic peptides to treat the auto-antibody-mediated propagation of heart failure. These cyclic peptides reduce stimulatory antibodies by immune interference. In disease models, they prevented the generation of heart failure and also reversed existing heart failure. 

Cyclic peptides for the treatment of chronic congestive heart failure have already been tested in humans in a placebo-controlled trial, and were shown to be well tolerated. They showed good efficacy to neutralize anti-ß1 receptor autoantibodies.

In June 2012, this development project was sold to Janssen-CILAG GmbH, a subsidiary of Johnson + Johnson, New Brunswick, NJ, USA. A price of 100 million USD for the respective company Corimmun GmbH was paid subsequently, and further milestone-dependent payments and royalties were agreed. This payment therefore allowed for a substantial return on the prior investments by (semi-)public institutions using taxpayer money  (e. g. grants by the German Research Ministry (BMBF) or investments by Kreditanstalt für Wiederaufbau (KfW) or HighTechFonds): In addition to relevant investments by private fonds, these (semi-)public institutions had contributed 10.4 million EUR from 2008 to 2012. From 2012 to 2014, an overall sum of 52.6 million EUR was paid back to these institutions or as taxes.

A Phase II study was carried out in patients with chronic heart failure (NCT01391507). This study was terminated early and converted to a pilot study by the sponsor Janssen (J+J) for strategic, but not for medical reasons.

The further clinical development of COR-1 is currently being organized by the University of Würzburg, Germany, which still holds the proprietary rights on the patents. An additional phase IIb study is currently being prepared at the German Comprehensive Heart Failure Centre (EudraCT 2015-002010-68)

 

References

Anti-TSH receptor-mediated thyroid disease (Graves´ disease)

These auto-antibodies are directed against native thyroid stimulating hormone (TSH) receptors in the thyroid gland, which they activate like the naturally occurring hormone TSH. This mechanism leads to a chronic excess stimulation of these important regulatory receptors and consecutive hyperthyroidism.

Novel cyclic peptides effectively treat the auto-antibody-mediated propagation of hyperthyroidism. They reduce stimulatory antibodies by immune interference. In disease models, the cyclic peptides successfully improved goiters (thyroid enlargements) and hyperthyroidism and also cured eye symptoms (“auto-immune orbitopathy”) which frequently occur in this condition and are especially hard to treat.