A Life Too Short

Countless rare diseases remain uninvestigated by big pharma, leading non-profit organizations to step up to the challenge themselves. In the case of the Progeria Research Foundation (PRF), their efforts have resulted in gold – for the first time ever a drug has been shown to increase survival. Clinical trials that increase survival are always heartening, but even more so when the patients are children.

“Progeria is a rare, fatal, pediatric disease that causes rapid aging. Without progeria-specific treatment, children with progeria will die of heart disease at an average age of 14 years,” says Leslie Gordon, medical director and co-founder of PRF. “The Progeria Research Foundation was founded in 1999 by the parents of a child with progeria, in response to a complete lack of medical and scientific progress to help these children.”

Working with patient families, pediatricians, and academic researchers, PRF has uncovered a number of scientific insights into progeria.over the last two decades. The disease is caused by a genetic mutation in the LMNA (lamin A) gene, and results in the over-production of a protein called progerin, which causes premature aging of the body’s cells. After the gene discovery, PRF-funded researchers began an intense study of progerin and its post-translational processing.  “There is a real biological link between progeria and normal aging. We now know that progerin is made in all of us, but at a much lower rate than in children with progeria. Progerin is found in cells of the cardiovascular system and increases at about 3 percent each year that we age,” says Gordon.

The discovery led researchers to investigate Farnesyltransferase inhibitors (FTIs), particularly FTI lonafarnib, which has mainly been studied in solid tumors. To block normal cell function and cause progeria, a farnesyl group attaches to the progerin protein. Since FTIs inhibit attachment of the farnesyl group, it was theorized that they could help progeria patients.

Treatment with lonafarnib alone compared with no treatment was associated with a significantly lower mortality rate (3.7 percent versus 33.3 percent) after a median of 2.2 years of follow up (1). “This is an incredibly short amount of time to achieve statistical significance. And we also have supportive data that we have previously published showing lonafarnib’s influence on the cardiovascular system and skeletal systems. It shows us that we can make progress,” says Gordon.

But she also stresses that pharma needs to do more to support rare diseases. PRF is hoping to eventually see lonafarnib become FDA approved – but that’s a huge challenge for a non-profit organization and its collaborators. “We need to fund much more research into progeria. There are brilliant scientists that can help us make big breakthroughs, but we need to support their efforts,” says Gordon. “The only way to treat and cure these fatal diseases is to work together – the rare disease communities, patient organizations, academia, the National Institutes of Health, the FDA and pharma. I’ve love to see more incentives and rewards for pharma to get involved with rare diseases. This is an opportunity to save children – and make new discoveries in aging and atherosclerosis.”