Progeria 101 / FAQ

Because of the historic Progeria gene discovery, we have a definitive, scientific way to diagnose the children. This results in more accurate and earlier diagnoses so the children can receive proper care. The Progeria Research Foundation has a Diagnostic Testing Program that looks at the specific genetic change, or mutation, in the Progeria gene that leads to HGPS. After an initial clinical evaluation (looking at the child’s appearance and medical records), a sample of the child’s blood is tested for Progeria.  Genetic testing is also available at some genetic diagnostics facilities.  Accompanying genetic counseling is always advised.

History was made in September 2012, when the results of the first-ever progeria clinical drug trial demonstrated that lonafarnib, a farnesyltransferase inhibitor (or FTI), was an effective treatment for Progeria.[5]  All trial participants experienced significant improvements in weight gain, bone structure, and most importantly, the cardiovascular system.

A subsequent 2018 study published in the Journal of the American Medical Association (JAMA) demonstrated that lonafarnib helped extend survival in children with Progeria.[6]

These studies led to the extraordinary 2020 U.S. Food & Drug Administration (FDA) approval of  lonafarnib as the first-ever treatment for Progeria. An important piece of PRF’s mission, this approval was the culmination of 13 years of clinical research involving four clinical trials, bringing 96 children from 37 countries to Boston for treatment.

Without lonafarnib, the only approved drug to treat Progeria, the children die of atherosclerosis (heart failure or strokes) at an average age of 14.5 years)[7].  With lonafarnib treatment, average age of death is extended by at least 2.5 years (research on this is ongoing).

With this milestone, Progeria joined the ranks of fewer than 5% of rare diseases with an FDA-approved treatment.

In some cases, surgery to insert new heart valves or open blood vessels supplying the heart (stents) has also helped to improve the health of patients in later stages of disease.

In pursuit of our mission to discover additional treatments and the cure for Progeria, PRF is funding cutting-edge research initiatives exploring drugs and methods that target the various pathways throughout Progeria disease progression. Those areas address: 1) correcting the LMNA mutation by genome editing; 2) inhibiting progerin mRNA production with RNA therapeutics; and 3) influencing progerin protein, or proteins that interact with or act downstream of progerin using drugs called small molecules.

1. Gene therapy: In January 2021, the science journal Nature published breakthrough results demonstrating that genetic editing in a mouse model of Progeria corrected the Progeria mutation in many cells, improved several key disease symptoms and increased lifespan in the mice by 240%.[8] Additional preclinical studies are needed to investigate these results, which we hope will one day lead to a clinical trial.

“To see this dramatic response in our Progeria mouse model is one of the most exciting therapeutic developments I have been part of in 40 years as a physician-scientist,” said Francis Collins, MD, PhD, Director of the National Institutes of Health.

2. RNA Therapeutics: In March 2021, PRF contributed to two very exciting breakthrough studies on the use of RNA therapeutics in Progeria research, both of which attempt to block the body’s ability to produce progerin production at the RNA level. One study showed that treating Progeria mice with a drug named SRP2001 reduced the harmful progerin mRNA and protein expression in the aorta, the main artery in the body, as well as in other tissues. At the end of the study, the mice demonstrated an increased survival of over 60% [9].The other study showed a 90 – 95% reduction of the toxic progerin-producing RNA in different tissues after treatment with a drug called LB143. Progerin protein reduction was most effective in the liver, with additional improvements in the heart and aorta.[10]
3. Targeting the progerin protein through small molecule drug development: A drug called progerinin has shown great promise. In a Progeria mouse model, progerinin increased body weight and extended lifespan by 10 weeks, a substantial breakthrough, compared with lifespan extension of two weeks in lonafarnib-treated mice.[11] Another molecule with exciting potential targets the pro-inflammatory cytokine interleukin 6 (IL6) by repurposing tocilizumab, a drug approved for treating human arthritis. Progeroid mice treated with tocilizumab showed skin improvements, weight gain, better locomotor activity, and lifespan extension.

The field of Progeria research is making major advancements, continuously growing in scope and sophistication as the search for effective treatments and the cure continues. Devoted, diligent scientists are leading the field to breakthroughs and new treatments that help children with Progeria live longer, healthier lives, while also driving discovery in heart disease and aging.