Abstract Number: 11

Genetic disorders update: Therapeutic advances

A.S. Paller

Meeting: 2014 Dermcoll

Session Information

Date: -

Session Title: Plenary Session 1

Session Time: -

The underlying molecular cause has been determined for
hundreds of monogenic genodermatoses. The more recent
availability of next-generation sequencing, in particular, is
rapidly leading to the discovery of the cause of rare
monogenic disorders, helping to analyze more complex
genetic disorders, illuminating genotype-phenotype corre-lations, and uncovering the basis for mosaic genetic
disease, helping us to understand how gene changes translate
into clinical manifestations. Our great progress in
understanding genetic disease has revolutionized prenatal
diagnosis, and has allowed families to avoid termination
through preimplantation diagnosis, which utilizes in vitro
fertilization. Importantly, our understanding of gene and
resultant protein changes is translating into new
pathogenesis-based therapy for our patients through
pharmacogenomics (to pharmacologically adjust gene and
protein expression), signaling pathway manipulation, and
by directly altering gene expression (through gene introduction
or by suppressing specific gene overexpression or
mutations). Examples of pharmacologic therapy are use of
small molecule inhibitors to block activated signaling pathways
in tumor syndromes, replacement therapy (or replacement
therapy coupled with pathway inhibition), and
theoretically agents that may induce a compensatory proteins,
such as for epidermolysis bullosa simplex or
ichthyosis vulgaris. Gene therapy approaches range from
cell therapy through direct injection, grafting or stem cell
introduction to suppression of dominant negative defects by
siRNA introduction or Talens. Finding areas of revertant
mosaicism or use of induced pluripotent stem cells can
facilitate these genetic approaches. Ultimately, new technologies
for identification of genetic alterations and managing
their results are rapidly moving us into the area of
personalized pharmacologic-based and gene-based
therapy.