Brian Capell and his colleagues at the National Human Genome Research Institute (NHGRI) reported that drugs known as farnesyltransferase inhibitors (FTIs), which are currently being tested in people with myeloid leukemia, neurofibromatosis and other conditions, might also provide a potential therapy for children suffering from Hutchinson-Gilford Progeria Syndrome, commonly referred to as progeria.
There are currently no treatments for progeria, which is a genetic disorder estimated to affect one child in four million. When they are born, children with progeria appear normal. But, as they grow older, they experience growth retardation and show dramatically accelerated symptoms of aging – namely hair loss, skin wrinkling and fat loss. Accelerated cardiovascular disease also ensues, typically causing death from heart attack or stroke at about the age of 12.
“Our findings show that FTIs, originally developed for cancer, are capable of reversing the dramatic nuclear structure abnormalities that are the hallmark of cells from children with progeria. This is a stunning surprise, rather like finding out that the key to your house also works in the ignition of your car,” said NHGRI Director Dr Francis Collins, who is the study’s senior author.
The new work involved using FTIs to treat skin cells taken from progeria patients and grown in laboratory conditions. If upcoming studies in a mouse model validate the results of the cell experiments and translate into improvements in the animals’ conditions, a clinical trial of FTIs in children with progeria may begin as early as next spring, researchers said.
Dr Collins and his colleagues discovered in April 2003 that mutations in the lamin A (LMNA) gene cause progeria, spurring renewed interest among researchers to study this rare syndrome.