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New approach to treating congenital ichthyosis
A team led by former BIH professor Prof. Dr. Sarah Hedtrich focused on a form of fish scale disease known as autosomal recessive congenital ichthyosis (ARCI). This is a rare, hereditary skin disorder that disrupts the formation of the body's skin cornea. Those affected often have dry, reddened and scaly skin that can be very itchy and tight. Until now, only the symptoms of ARCI could be treated. The team has now developed a treatment method that can correct the mutation in the gene that causes ARCI. The problem: Gene therapies that are applied to the skin, which are supposed to be transported to the right place via small fat globules (lipid nanoparticles), are difficult to absorb due to the skin's protective barrier. The researchers have now found a way to modify the skin barrier to make this possible. The project was funded by SPARK BIH. We spoke to Prof. Hedtrich about this approach.
What problem did your team attempt to solve with this translational research project?
There is currently no effective treatment for patients with ARCI. Until now, they have had to rely exclusively on symptomatic treatment, which has only a very limited effect. The approach presented here represents the first real treatment option for those affected, who suffer greatly from their often stigmatising skin condition – with serious consequences such as social isolation and depression. In addition, mortality is increased in newborns with ARCI. We therefore see the possibility of treating particularly vulnerable children immediately after birth in order to reduce their suffering and minimise risks associated with ARCI at an early stage.
This is the world's first gene therapy for ARCI. To date, there is only one other gene therapy for a different skin disease, in which patients with epidermolysis bullosa – a rare, blistering skin disease – have a missing gene replaced. In contrast to this viral vector-based approach, the method presented here is scalable, more cost-effective and shows lasting and potentially curative treatment effects.
What specific challenges did you face in developing your approach?
Human skin is a very effective protective barrier whose main task is to prevent the penetration of external influences such as pathogens. This makes it particularly difficult to transport large molecules – such as genetic material – into the skin and deliver them to exactly the right place. We have developed a special approach to this problem that enables the gene scissors, packaged in lipid nanoparticles, to be introduced into the skin in a targeted manner. To do this, a laser is used to create small micropores in the skin, through which the lipid nanoparticles can penetrate more easily. Another challenge was that there were no precedents for our approach, which could lead to additional hurdles, especially with regard to the planned application in humans.
What significance could this success have for patients?
In this study, we show that disease-causing mutations in human skin can be corrected locally using a topical, i.e. externally applied, non-invasive approach. The method is clinically relevant, safe, scalable and easy to use. It is particularly important that our approach targets the cause of the disease directly. Our data suggest that a single treatment may be enough to potentially cure the disease. In summary, this could represent a significant milestone in the treatment of ARCI patients and has the potential to fundamentally change the therapy of this previously incurable disease.
How do you plan to apply the technology to other diseases in the future, and if so, which ones?
The approach we have developed is a platform technology that can be easily adapted to other genetic ‘cargo’ and other skin diseases – and potentially even beyond. We are currently working on similar therapies for other rare skin diseases and are also investigating its possible use in common skin problems such as atopic dermatitis. In quite a few patients with severe atopic dermatitis, a genetic defect plays a decisive role.
Did you establish a spin-off based on this technology?
Based on our development, we founded the spin-off Epithelica in 2025, which is now working on bringing our therapy to patients and, in the long term, to market. We are currently in the fundraising phase in order to start the clinical trial and make all the necessary preparations for treatment. This step brings us one important step closer to making the therapy a reality for those affected.
