Inherited ichthyoses are rare genetic diseases (prevalence 13.3 per million in Europe) that occur at birth or early infancy, causing abnormal scaling, skin thickening, dryness, itching and pain. Despite strong genetic heterogeneity, about half of the patients, particularly those with Autosomal Recessive Congenital Ichthyosis (ARCI), display a primary genetic defect characterized by impaired metabolism of a critical ceramide called CerEOS, which is essential for building a healthy epidermal barrier.
Current treatments for ichthyoses are symptomatic, untargeted and minimally effective, with potential serious side effects. Emerging therapies, like biologics and defective product replacement, are in early development stages.

A promising approach is replacing deficient CerEOS to improve the epidermal barrier. However, existing ceramide-containing creams are ineffective due to the difficulty in delivering these challenging-to-synthesize and poorly soluble lipids. In 2022, we formed a multidisciplinary consortium for preclinical development of lipid replacement therapy for ichthyoses with impaired CerEOS synthesis (project LIPARCI). CerEOS was synthesized and encapsulated in nanoparticles called lamellar body mimetic systems (LBms). These innovative LBms allowed delivery of the skin-identical lipid in a CerEOS deficient organotypic model of ARCI improving the epidermal barrier. A formulation will be tested in a dog model of ARCI in 2024.

LIPARCI II aims to reinforce our preclinical data, starts a first-in-human clinical testing (phase 0) to assess the bioavailability of our formulation and initiates scale-up production of the CerEOS LBms. Additionally, we will develop in vitro models targeting genes involved in CerEOS processing, expanding potential patient pool. This involves synthesizing a new ceramide, the downstream metabolite of CerEOS, and testing new LBms. Overall, our goal is to develop an advanced therapy medicinal product based on disease pathogenesis.