DRUGSFORD

Preclinical development of drugs and drug delivery technology for the treatment of inherited photoreceptor degeneration

01.09.2012 bis 31.08.2016

https://www.drugsford.eu/

Dysregulation of cGMP is a pathological hallmark of inherited retinal degenerations (RD) affecting photoreceptors, the sensory cells of the retina. These RDs, including Retinitis Pigmentosa, Lebers Congenital Amaurosis, and Achromatopsia, are major causes of blindness, affecting approximately one in every 2000 individuals worldwide. They still remain without effective treatment. In photoreceptors, cGMP is
produced by retinal guanylyl cyclase (GC). The two main cGMP targets are cyclic nucleotide gated ion channels (CNGC) and cGMP-dependent protein kinase (PKG). Since attenuation of PKG and CNGC activity reduces photoreceptor cell death, both proteins constitute potential targets to prevent photoreceptor degeneration. Recent data suggests that blocking retinal GC may also constitute a viable therapeutic approach.
This consortium will study and develop targeted compounds and delivery systems preventing photoreceptor damage in preclinical disease models. Towards this goal, two SMEs have teamed up with three academic research groups focussed on retinal degeneration: the German company BIOLOG specializes in developing cyclic nucleotide based drugs targeting PKG, CNGC, and GC; the Dutch company to-BBB
develops systems to deliver drugs across the blood brain/retinal barrier (BBB, BRB, resp.); the groups of V. Marigo (Modena, Italy), P.
Ekström (Lund, Sweden), and F. Paquet-Durand (Tübingen, Germany) have a strong and joint collaborative track record of studying
of cGMP is a pathological hallmark of inherited retinal degenerations (RD) affecting photoreceptors, the sensory cells of the retina. These RDs, including Retinitis Pigmentosa, Lebers Congenital Amaurosis, and Achromatopsia, are major causes of blindness, affecting approximately one in every 2000 individuals worldwide. They still remain without effective treatment. In photoreceptors, cGMP is produced by retinal guanylyl cyclase (GC). The two main cGMP targets are cyclic nucleotide gated ion channels (CNGC) and cGMP-dependent protein kinase (PKG). Since attenuation of PKG and CNGC activity reduces photoreceptor cell death, both proteins constitute potential targets to prevent photoreceptor degeneration. Recent data suggests that
blocking retinal GC may also constitute a viable therapeutic approach.
This consortium will study and develop targeted compounds and delivery systems preventing photoreceptor damage in preclinical disease models. Towards this goal, two SMEs have teamed up with three academic research groups focussed on retinal degeneration: the German company BIOLOG specializes in developing cyclic nucleotide based drugs targeting PKG, CNGC, and GC; the Dutch company to-BBB develops systems to deliver drugs across the blood
brain/retinal barrier (BBB, BRB, resp.); the groups of V. Marigo (Modena, Italy), P. Ekström (Lund, Sweden), and F. Paquet-Durand (Tübingen, Germany) have a strong and joint collaborative track record of studying photoreceptor degenerative mechanisms as well as on testing and evaluating drug treatment effects. Manufacture of the most promising drugs fitted to a suitable delivery system will be scaled up towards clinical-size batches and studied regarding efficacy, toxicology and off-target effects in model animals.