Challenges in Treating Genodermatoses: New Therapies at the Horizon

Area of Science:

• Dermatology
• Genetics
• Molecular Biology
• Translational Research

Background:

• Genodermatoses are rare inherited skin diseases with significant impact on wellbeing and survival.
• Molecular genetics advancements have elucidated disease mechanisms and paved the way for novel therapeutic strategies.
• Many genodermatoses present high unmet medical needs, necessitating innovative treatment approaches.

Purpose of the Study:

• To review and discuss the potential advantages and drawbacks of emerging therapeutic technologies for genodermatoses.
• To highlight personalized treatment strategies tailored to specific genetic defects and mutations.
• To emphasize the importance of reproductive choices and genetic testing for preventing disease transmission.

Main Methods:

• Targeting dysregulated cell-signaling pathways with inhibitors or augmentation.
• Utilizing repurposed drugs for 'read through' strategies in premature termination codon mutations.
• Employing cell therapies (keratinocytes, fibroblasts, bone marrow, mesenchymal cells) for tissue repair and organ rescue.
• Exploring gene therapy, including gene insertion and genome editing (CRISPR-Cas9).
• Applying RNA interference (RNAi) to reduce harmful protein expression.

Main Results:

• Several therapeutic strategies are in preclinical or clinical trial phases.
• Gene insertion and genome editing in stem cells show potential for permanent cures.
• Short-lasting strategies require intermittent, lifelong administration.
• Personalized approaches are crucial due to the heterogeneity of genodermatoses.

Conclusions:

• Emerging technologies offer promising therapeutic avenues for genodermatoses.
• Gene and cell therapies, particularly those targeting stem cells, hold potential for permanent correction.
• Reproductive genetic testing is vital for preventing transmission of these severe inherited conditions.