Publications

Repurposing of drugs to treat rare diseases (RDs) is vital, but the translational gap between clinical evidence and regulatory approval remains unquantified. Analysis of 47 clinical trials showed that 66% of completed studies met their primary or key secondary endpoints. Nevertheless, only 39% ac...

UV radiation (UVR) drives high mutational burdens, yet precursor melanocytes accumulate these mutations without triggering immune clearance. Here, we investigated whether melanocyte-intrinsic transcriptional program(s) underlie immune tolerance to mutations resulting from UVR exposure. In primary...

Duchenne muscular dystrophy (DMD) is a rare X-linked recessive disorder caused by mutations in the DMD gene, resulting in the absence of functional dystrophin. The loss of dystrophin disrupts the dystrophin-associated protein complex (DAPC), leading to progressive degeneration of skeletal and car...

Epidermolysis bullosa simplex (EBS) is a genetic skin disorder driven by dominant pathogenic variants in or genes, leading to cytoskeletal fragility in basal keratinocytes and intraepidermal blistering. No curative therapies are currently available, and the link between keratin mutations and di...

The classical paradigm of drug screening often faces significant limitations due to the challenges associated with identifying molecular or cellular read-outs that are relevant to specific genetic diseases. To remedy this, an alternative approach of reverse phenotypic mapping was tested: Compound...

Drug screening for genetic disorders is limited by difficulty identifying disease-relevant phenotypes. In this issue, Roussange et al., show that reverse phenotypic mapping could uncover therapeutic gene expression signatures. Using this approach, they identified prazosin, which increases SQSTM1 ...