Treatment with lonafarnib extends survival in children with Progeria: Study

A new study published in JAMA reports that an farnesyltransferase inhibitor (FTI), helps extend survival in children with HGPS

A new study published in The Journal of the American Medical Association (JAMA) reports that lonafarnib, a farnesyltransferase inhibitor (FTI), helped extend survival in children with Hutchinson-Gilford Progeria Syndrome (HGPS), or Progeria. Progeria is an ultra-rare and fatal disease that causes premature aging in children. Children with Progeria live an average 14 ½ years, dying from heart disease typically associated with old age. Authors from Boston Children’s Hospital and Brown University tracked more than 250 children from six continents to demonstrate a link between lonafarnib treatment and extended survival.

Progeria is caused by a genetic mutation that results in an overabundance of the protein named progerin. Accumulation of progerin within a cell is typically seen in normal aging, but the rate of accumulation is highly accelerated in Progeria, causing progressive cellular damage and resulting in atherosclerotic heart disease.

Lonafarnib, originally developed by Merck as a potential cancer therapeutic, inhibits farnesyltransferase, an enzyme that facilitates progerin production. The FTI prevents the mutant protein from incorporating into the cellular wall where it causes much of its damage.

In the clinical trial, 27 children with Progeria received oral lonafarnib (150 mg/m2) twice daily as a monotherapy. The control arm of this study consisted of children with Progeria with similar age, sex and continent of residency as the treated patients, who were not part of the clinical trial and therefore did not receive lonafarnib. The results demonstrated that treatment with lonafarnib alone compared with no treatment was associated with a significantly lower mortality rate (3.7 per cent vs. 33.3 per cent) after a median of 2.2 years of follow up.

The study was funded by the non-profit organisation, The Progeria Research Foundation (PRF).

“My lab did some of the original research on cellular and mouse models that showed potential benefit of this class of drugs for Progeria,” said Francis S. Collins, Director, National Institutes of Health. “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,” said Dr. Collins.

“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,” said Leslie Gordon,Co-founder and Medical Director, PRF, and lead study author. “These results provide new promise and optimism to the Progeria community,” said Dr Gordon.