Topical Recombinant Alpha1-Antitrypsin: A Potential Treatment for Netherton Syndrome?

rAAV2-mediated restoration of LEKTI in LEKTI-deficient cells from Netherton patients

“…In theory, protein replacement by means of topical application of recombinant LEKTI might allow LEKTI to permeate the impaired skin barrier of NS patients and become active at the granular layer and thus ameliorate LEKTI deficiency. Since recombinant LEKTI is yet not available, alpha1-antitrypsin has been tried topically instead, but had failed to be beneficial in NS [22]. Gene therapy is by far the more complex and complicated development for treating NS, but recent results from the first human skin gene therapy trial for hereditary epidermolysis bullosa were very encouraging and demonstrated that skin gene therapy is feasible and can lead to a ''cure'' of the underlying genodermatosis [23].…”

Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy

“…Topical calcipotriol was effective (Godic and Dragos, 2004), topical recombinant alpha1-antitrypsin (AAT) showed no effectiveness (Mazereeuw-Hautier et al, 2006). In contrast, intravenous immunoglobulins (IVIG) were successfully used in five children with NS (Renner et al, 2009).…”

Therapeutics and Other Interventions

“…One study treated patients with Netherton syndrome for 3 weeks with topically applied protease inhibitors. No effect compared with placebo could be documented [ 67 ]. Only fi ve subjects were included.…”