Children Aging Before Their Time: Can Progeria Now Be Treated?

Dr. Stephen Young presents the progress in understanding and treating Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder causing premature aging. He explains that HGPS is caused by a mutation in the LMNA gene, leading to an abnormal form of the protein prelamin A that remains farnesylated. This abnormal protein disrupts the nuclear lamina, causing misshapen nuclei and various symptoms. Young’s laboratory created mouse models of HGPS and demonstrated that treatment with farnesyltransferase inhibitors (FTIs), originally developed for cancer, can improve growth and reduce bone abnormalities in these mice. Based on these promising results, a clinical trial of FTIs in children with HGPS is underway. However, Young cautions that while FTIs show benefit, they may not be a complete cure, as the abnormal protein itself may still be toxic. He also discusses a serendipitous discovery that HIV protease inhibitors can inhibit the enzyme ZMPSTE24, leading to accumulation of farnesylated prelamin A and causing lipodystrophy in HIV patients. Finally, he highlights the importance of basic research in understanding the nuclear lamina and its implications for other diseases.