Clinical Trial Summary
The neurodegenerative disorders is a class o pathologies including very common diseases as
Alzheimer or Parkinson or very rare as fatal familial insomnia (FFI), the progression of the
disease with no therapeutic remedy is the common tract of these disorders. The aim of this
project is to carry out a preventive treatment in subjects with genetic risk to develop FFI
to avoid the establishment of the disease. FFI is a rare genetic neurodegenerative disease
characterized by disrupted sleep, autonomic hyperactivation and motor abnormalities with
fatal exitus. FFI is inherited in an autosomal dominant fashion and is linked to the D178N
mutation in the prion protein gene (PRNP) in association with a methionine at the polymorphic
codon 129 (D178N/M129). About thirty FFI pedigrees have been described worldwide, the mfirst
case being reported in 1986 in northern Italy. This patient turned out to belong to large
kindred, which spans 7 generations dating back to the eighteenth century. Many people
belonging to this geneaology still live in the Veneto region of Italy, and they are part of
an association. The genetic screening of 85 subjects belonging to this family permitted to
identify the mutation carriers. Since the disease is aggressive and the affected people
usually died within thirteen months from the onset, the possibility of an efficacious therapy
when the disease become evident is unrealistic. This condition indicates in a preventive
approach the better condition to affect the disease. Experimental studies and clinical
observation indicated the antibiotic doxycycline (DOXY) as a potential candidate for a
treatment in FFI subjects. The age with maximal risk to get the disease is between 50 and 55
years old. Thus the carriers that were born between 1958 and 1969 will be recruited for a
preventive treatment with DOXY for ten years, at the end of this period or before we can
establish if DOXY can be useful to avoid the development of FFI.
