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

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Drugs against inherited photoreceptor degeneration

European researchers investigated a novel pharmacological approach for inhibiting photoreceptor degeneration. The generated compounds showed significant preclinical efficacy and safety, potentially revolutionising treatment for patients suffering from hereditary retinal degeneration (RD).

Fundamental Research

RD constitutes a group of genetically and clinically heterogenous rare diseases associated with loss of photoreceptors, the light sensors of the retina. RD is still incurable and leads to blindness or severe vision loss. The disease pathophysiology often involves an accumulation of cGMP in the photoreceptors. The EU-funded DRUGSFORD (Preclinical development of drugs and drug delivery technology for the treatment of inherited photoreceptor degeneration) project proposed to rebalance the actions of cGMP and its targets by using cGMP analogues, compounds that mimic the structure of cGMP but do not cause the pathological downstream signalling events. DRUGSFORD generated cyclic nucleotides that can efficiently bind and inhibit cGMP targets, including protein kinase G (PKG) and the cyclic nucleotide gated channel (CNGC). To overcome the blood-retina-barrier and reach the photoreceptors of the retina, the consortium coupled these compounds with a glutathione-PEGylated liposomal drug delivery system. The lead compound DF003 was shown to efficiently inhibit both PKG and CNGC in vitro and demonstrated protective properties in several in vivo RD models. Importantly, it significantly increased photoreceptor viability, which was accompanied by a marked improvement of in vivo retinal function. In addition, in vitro and in vivo toxicity assessments revealed no major adverse effects of DF003 or its liposomal formulation. Overall, the DRUGSFORD study introduced a new class of compounds for RD treatment, inventively combined with an efficient retinal delivery method. The latter allowed sufficient drug concentration in photoreceptor cells regardless of the route of application (systemic or directly to the eye). Three patent applications were filed, and the DF003 lead compound also obtained an orphan drug designation (ODD) from the European Medicines Agency. To ensure that these research results will eventually be translated into a clinical treatment for RD, after the end of the DRUGSFORD project, the consortium partners have jointly founded a new company. This company – Mireca Medicines GmbH – is dedicated to collect the IP generated and pursue the clinical testing of DRUGSFORD compounds and drug delivery approaches.


Photoreceptor, hereditary retinal degeneration, cGMP, DRUGSFORD, PKG, CNG channel

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