Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment.

OBJECTIVES: The objective of this study was to retrospectively evaluate neurologic status pre- and posttreatment with the oral farnesyltransferase inhibitor lonafarnib in children with Hutchinson-Gilford progeria syndrome (HGPS), a rare, fatal disorder of segmental premature aging that results in early death by myocardial infarction or stroke.
METHODS: The primary outcome measure for intervention with lonafarnib was to assess increase over pretherapy in estimated annual rate of weight gain. In this study, neurologic signs and symptoms were compared pre- and posttreatment with lonafarnib.
RESULTS: Twenty-six participants were treated for a minimum of 2 years. Frequency of clinical strokes, headaches, and seizures was reduced from pretrial rates. Three patients with a history of frequent TIAs and average clinical stroke frequency of 1.75/year during the year before treatment experienced no new events during treatment. One patient with a history of stroke died due to large-vessel hemispheric stroke after 5 months on treatment. Headache prevalence and frequency were reduced. Four patients exhibited pretherapy seizures and no patients experienced recurrent or new-onset seizures.
CONCLUSIONS: This study provides preliminary evidence that lonafarnib therapy may improve neurologic status of children with HGPS. To address this question, we have incorporated prospective neuroimaging and neurologic assessments as measures in subsequent studies involving children with HGPS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that lonafarnib 115-150 mg/m(2) for 24 to 29 months reduces the prevalence of stroke and TIA and the prevalence and frequency of headache over the treatment period.