Hutchinson-Gilford Progeria Syndrome Case Study

Presentation Title: Hutchinson-Gilford Progeria Syndrome Case Study
Session 4: Beyond Surrogate Endpoints: Other Ways Translational Science Can Support Drug Development
Speaker: Leslie B. Gordon, MD, PhD

Summary:

Hutchinson-Guilford Progeria Syndrome is an ultrarare disease causing failure to thrive, premature aging, and cardiovascular symptoms including pediatric heart attacks and strokes. Bench research into the etiology of this disease revealed a mutation in the gene LMNA and the accumulation of a protein “progerin”, and helped inform a valuable transgenic mouse model and a potential drug target. Treatment with the farnesyltransferase inhibitor Lonafarnib improved cardiovascular outcomes in the mouse model, and showed similar success in cardiovascular outcomes and mortality in human clinical trials.

Key Takeaways:

• A transgenic mouse model helped establish evidence of effectiveness for progeria treatment in humans using Lonafarnib
• Successful collaboration between bench research and clinical research was essential to enable the translation of the therapies
• Animal models helped optimize care and produce statistically significant trial results despite a small patient population but can have limitations which are important to consider when applying findings to human populations
o Animal models may not always perfectly model disease progression in humans
o In order to develop a biologically relevant animal model, researchers had to induce cardiovascular disease and plaque calcification seen in human patients