Genetic Defect Identified as Underlying Cause of Epidermolysis Bullosa

A group of researchers from the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch, Germany have identified a genetic defect as the underlying cause of epidermolysis bullosa (EB), a gene that also explains why patients with EB have an increased sensitivity to touch and experience touch as painful. The new report found that patients with EB are deficient in laminin-332, a structural molecule in the skin that, in healthy people, slows the transduction of tactile stimuli and neuronal branching. Through their experiments with cell cultures, the researchers found that physical stimuli triggered ion currents in all neurons that were not surrounded by laminin-332. Additionally, sensory neurons in the skin tissue of patients with EB showed much more branching than the neurons of individuals without the condition. According to professor Gary R. Lewin of the MDC, patients with EB have neurons that are excited much more strongly than the neurons of healthy individuals, preventing the suppression of the transduction of a stimulus. As a result, “their sensory neurons are excited much more strongly, and thus they react much more sensitively to mechanical stimuli,” said Professor Lewin. This genetic defect that results in EB causes the epidermis of patients to separate from the dermis, which results in blisters. Laminin-332 is typically found between these two layers of skin and serves as a sort of “glue” between the two, according to the researchers. The researchers now hope that therapeutic drug targets can be identified, while also acknowledging that this study is significant regardless of any forthcoming results. “Because the causal mechanisms are now understood, we can focus on the patient’s pain situation and on administering more efficient pain therapies,” Professor Lewin said. “We recommend that in treating the disease, neurologists should be consulted in addition to dermatologists.” Results of this study were also published in a recent online edition of Nature Neuroscience.