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.
Name: Normal saline (placebo)
There is one SNP
We propose to perform a Phase Ib clinical trial to test the safety and tolerability of TD101 in PC patients carrying an N171K mutation. --- N171K ---
Inclusion Criteria: - A positive genetic identification of the N171K mutation in the keratin 6a gene from a CLIA certified laboratory; - Witnessed, signed informed consent approved by Institutional Review Board/Ethics Committee; - A signed Health Information Portability and Accountability Act (HIPAA) authorization form which permits the use and disclosure of patient's individually identifiable health information for those enrolled in the United States of America; - Male or female subjects of any race 10 years of age and older; - Complete physical examination and medical history indicating no abnormalities that will interfere with study objectives; - Normal or not clinically significant baseline laboratory tests, including hemogram, ANA, serum chemistry panel, urinalysis, C3a, Bb, and APTT,PT; - Negative pregnancy test (females only). --- N171K ---