Progeria Treatment Extends Survival in Children

Recently, a study in The Journal of the American Medical Association (JAMA) reported that lonafarnib helped to extend survival in children with Hutchinson-Gilford Progeria Syndrome (HGPS), or Progeria.

Leslie Gordon, MD, PhD, co-founder and Medical Director for PRF and lead study author, highlighted the significance of the study and its findings. "This study published in JAMA shows for the first time that we can begin to put the brakes on the rapid aging process for children with Progeria. These results provide new promise and optimism to the Progeria community.”

Lonafarnib is an orally active inhibitor of farnesyltransferase, an enzyme that moderates progerin production.

Progeria is characterized by a genetic mutation that causes an overabundance of the protein progerin. Due to the accelerated rate of accumulation in the cell (typically seen in normal aging), progressive cellular damage occurs, resulting in atherosclerotic heart disease. Children with progeria live for an average of 14^1/2 years.

More than 250 children from 6 continents who were tracked by authors from Boston Children's Hospital and Brown University displayed a link between lonafarnib treatment and extended survival. The Progeria Research Foundation (PRF), a non-profit organization, funded the study.

Twenty-seven children with Progeria received oral lonafarnib (150 mg/m²) twice daily as a monotherapy in the clinical trial. Children with progeria with similar age, sex, and continent of residency to the treated patients who were not part of the clinical trial and therefore did not receive lonafarnib composed the control arm of the study. A significantly lower mortality rate (3.7% vs. 33.3%) after a median of 2.2 years of follow-ups were associated in individuals with progeria who were administered lonafarnib alone as compared to no treatment.¹

National Institutes of Health (NIH) Director, Francis S. Collins, MD, PhD, commented on the study’s positive findings. "My lab did some of the original research on cellular and mouse models that showed potential benefit of this class of drugs for Progeria. It was encouraging to see those results translated into a clinical trial. Yet demonstrating effectiveness of treatments in this small population of children with this rare fatal disease is a major challenge. Thus, I'm particularly encouraged by these latest findings.”

PRF has funded hundreds of scientific studies and 4 clinical trials aimed at discovering new treatments and the cure for children with Progeria. Lonafarnib has been previously linked to improvements in clinical trial endpoints associated with atherosclerosis and stroke, which are 2 prime outcomes of Progeria.

There are approximately 110 diagnosed and 250 undiagnosed children worldwide; Progeria occurs in 1 in 20 million people.

Meryl Fink, President and Executive Director of PRF, reiterated the impoirtance of this study and others like it. “This study shows us that the clinical trials conducted today are our best hope for saving for these children in the future. “Based on the promising results from this study with lonafarnib, we feel a stronger sense of urgency than ever. Today's milestone marks a new beginning for these children and their families. Every day and every moment count. PRF's goal is to find the cure for Progeria and this study brings us one more step towards that goal.”

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References:

1. Global Study Published in JAMA Finds Treatment with Lonafarnib Extends Survival in Children with Progeria. https://www.prnewswire.com/news-releases/global-study-published-in-jama-finds-treatment-with-lonafarnib-extends-survival-in-children-with-progeria-300635360.html. Accessed April 24, 2018.