Study of TD101, a Small Interfering RNA (siRNA) Designed for Treatment of Pachyonychia Congenita
Status:
Completed
Trial end date:
2008-08-01
Target enrollment:
Participant gender:
Summary
Pachyonychia congenita (PC) is a rare, autosomal dominant keratin disorder affecting the
nails, skin, oral mucosae, larynx, hair and teeth. Pathogenic mutations in keratin K6a, K6b,
K16 or K17 act via a dominant negative mechanism, leading to manifestations of the disease.
The most disabling PC symptom is a painful plantar blistering and keratoderma that requires
use of ambulation devices in more than 50 percent of patients. Despite our understanding of
the molecular basis of PC, current treatment is limited to mechanical removal of the thick
calluses, non-specific topical keratolytics, and oral retinoids, none of which alleviates
blistering or plantar pain satisfactorily. A public charity, PC Project, has been founded to
support the development of treatments for PC (www.pachyonychia.org). In collaboration with
this charity, a small company, TransDerm, Inc., has developed a small interfering RNA (siRNA)
that specifically targets a mutation in one of the PC keratins, K6a. As this siRNA targets a
single nucleotide mutation, it will only be effective against PC subjects harboring this
specific mutation. There are currently only six known patients who carry this mutation in the
International Pachyonychia Congenita Research Registry, but three of these patients live in
Salt Lake City (a mother and two of her children). We propose to perform a Phase Ib clinical
trial to test the safety and tolerability of TD101 in PC patients carrying an N171K mutation.
We will complete treatment of the adult patient prior to recruitment of the minors.