Familiar Fatal Insomnia: Preventive Treatment With Doxycycline in Subject With Disease Risk

• Status: Completed
• Trial end date: 2021-04-12
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborator: Fondazione Telethon
• Treatments: Doxycycline

Criteria

Inclusion Criteria:

• subjects aged 44 to 53 years;

• no conditions known to be contraindications to the use of tetracyclines;

• written informed consent.

Exclusion Criteria:

• end stage liver,

• heart and renal disease,

• active malignancy,

• female subjects who are pregnant or lactating