The role of the farnesyltransferase inhibitor lonafarnib in the treatment of Progeria

Abstract

Introduction: Hutchinson–Gilford progeria syndrome (Progeria) is a rare autosomal dominant premature aging disease caused by the generation of progerin, a farnesylated, disease-generating counterpart to the nuclear protein lamin A.

Areas covered: The farnesyltransferase inhibitor (FTI) lonafarnib (SCH66336) is thought to reduce the deleterious effects of progerin by inhibiting the transfer of the farnesyl group onto this abnormal pre-lamin A molecule. The results of the first prospective clinical trial of lonafarnib in children with Progeria have recently been reported. In this review, the biologic basis of Progeria and the rational use of the FTI lonafarnib in this disease will be discussed. The results of this trial will be considered both in the context of the areas where lonafarnib demonstrated activity and areas of lack of response, as well as the toxicity of this agent.

Expert opinion: The FTI lonafarnib has demonstrated significant clinical activity in patients with Progeria. This approach will be only the first step in the long-term treatment of these patients as the field moves toward treating the underlying genetic abnormalities. New clinical trials combining multiple agents to better modulate the production of progerin are now underway.

Keywords::

• clinical trial
• farnesyltransferase inhibitor
• Hutchinson–Gilford progeria syndrome
• lonafarnib
• Progeria
• SCH66336

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