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.
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 250 genes.
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.
TWO main challenges for establishing therapies
- The blood-retinal barrier, shielding the retina and its photoreceptors from pathogens, toxins, etc., but which also prevents access for therapeutic compounds.
- 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
- Mireca applies a liposomal drug delivery technology which uses glutathione (GSH) to transfer therapeutic compounds across the blood-retinal barrier.
- 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.
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
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