Seeking a Cure for One of the Rarest Diseases: Progeria

Article, see p 114More than 5700 human conditions have now had their molecular causes defined, the majority of which are rare diseases that were molecularly characterized in the past 25 years.1 Yet, even today, approved therapies exist for only ≈500 of these conditions.2 Clearly, an urgent need exists for therapeutic advances to help people suffering from rare diseases, a need fraught with many challenges.The private sector’s interest in developing molecularly targeted therapies has been growing but still remains quite limited for the rarest diseases that have very little market potential. Given the costs, it is difficult to embark on such a therapeutic development effort from scratch; historically, the failure rate is very high, and it has taken an estimated 14 years and several billion dollars to develop and gain approval for a therapy aimed at a molecular target.2 The National Institutes of Health is working to overcome these obstacles through a variety of innovative efforts at its National Center for Advancing Translational Sciences, with repurposing of compounds developed for other applications being one particularly attractive option.A poignant example of the pressing need for effective treatments is one of the rarest of rare diseases: Hutchinson-Gilford progeria syndrome (HGPS), and this issue of Circulation reports the results of a triple-combination therapy trial for HGPS.3 Characterized by accelerated aging, HGPS has a prevalence of ≈1 in 20 million living individuals or ≈350 children worldwide at any given time. Without treatment, children with HGPS, who have completely normal intellectual development, die of atherosclerotic cardiovascular disease at the average age of 14.6 years.4,5In 2003, my laboratory at the National Institutes of Health and another group in France determined that HGPS is caused by a point mutation (C-to-T) in the lamin A ( LMNA ) gene. The …