Protecting eyesight with a small molecule in a broad band of mutations


Targeted cGMP analogues show promising data.

Patient need


Inherited retina degeneration like Retinitis Pigmentosa (RP), Leber's congenital amaurosis (LCA) and Stargardt's disease (STGD) lead to severe vision impairment or blindness. Each indication is characterized by a different age of disease onset and speed of degeneration.

Disease Mechanism

A newly discovered cell death mechanism shows that photoreceptor cells degenerate and eventually die due to excessive cGMP signaling. This principal disease mechanism is caused by a large number of mutations in over 270 genes.

Patient numbers

Retinitis Pigmentosa (RP), Leber congenital amaurosis (LCA) and Stargardt disease (STGD) are each orphan diseases with a combined patient number of about half a million in Europe, North America and Japan.


Mode of Action

© Mireca Medicines GmbH

© Mireca Medicines GmbH

TWO main challenges for establishing therapies

  1. The blood-retinal barrier, shielding the retina and its photoreceptors from pathogens, toxins, etc., but which also prevents access for therapeutic compounds.

  2. The enormous genetic diversity of hereditary retinal degeneration, which would in principle require establishing a new gene therapy for each individual gene mutation.

Two major innovations introduced by mireca

  1. Mireca applies a liposomal drug delivery technology which uses glutathione (GSH) to transfer therapeutic compounds across the blood-retinal barrier.

  2. Mireca introduces cGMP analogues as a new class of therapeutic compounds that can interfere with excessive cGMP-signaling in photoreceptors. Importantly, excessive cGMP signaling is a phenomenon common to many, if not most, forms of hereditary retinal degeneration, thus allowing to treat many of these diseases with the same therapeutic compound.


Scientific output

Reading List

Wang T, Tsang SH, Chen J: Two pathways of rod photoreceptor cell death induced by elevated cGMP, Hum Mol Genet. 2017 Apr 3. doi: 10.1093/hmg/ddx121

Sothilingam V et al.: Retinitis pigmentosa: impact of different Pde6a point mutations on the disease phenotype, Hum Mol Genet. 2015 Oct 1;24(19):5486-99

Arango-Gonzalez B et al.: Identification of a common non-apoptotic cell death mechanism in hereditary retinal degeneration, PLoS One. 2014 Nov 13;9(11):e112142

Xu J et al.: cGMP accumulation causes photoreceptor degeneration in CNG channel deficiency: evidence of cGMP cytotoxicity independently of enhanced CNG channel function. J Neurosci. 2013 Sep 11;33(37):14939-48

Sahaboglu A et al.: Retinitis pigmentosa: rapid neurodegeneration is governed by slow cell death mechanisms, F. Cell Death Dis. 2013 Feb 7;4:e488. doi: 10.1038/cddis.2013.12

Schlossmann J, Schinner E: cGMP becomes a drug target, Naunyn Schmiedebergs Arch Pharmacol. 2012 Mar;385(3):243-52

Trifunović D et al.: Neuroprotective strategies for the treatment of inherited photoreceptor degeneration, Curr Mol Med. 2012 Jun;12(5):598-612

Paquet-Durand F et al.: A key role for cyclic nucleotide gated (CNG) channels in cGMP-related retinitis pigmentosa, Hum Mol Genet. 2011 Mar 1;20(5):941-7

Paquet-Durand F et al.: PKG activity causes photoreceptor cell death in two retinitis pigmentosa models, J Neurochem. 2009 Feb;108(3):796-810

Farber DB, Lolley RN: Cyclic guanosine monophosphate: elevation in degenerating photoreceptor cells of the C3H mouse retina, Science. 1974 Nov 1;186(4162):449-51

INtellectual property

PCT/EP2016/055659, Targeted liposomal delivery of cGMP analogues

PCT/EP2017/066113, PKG antagonists (Inhibitors)

PCT/EP2017/071859, PKG agonists (Activators)

ODD EU/3/15/1462, LP-DF003 for Retinitis Pigmentosa