Children with Hutchinson-Gilford Progeria Syndrom have an average life expectancy of around 15 years as they develop aging symptoms. Photo courtesy of Progeria Research Foundation
April 27 (UPI) -- Scientists have developed a way to treat a genetic premature ageing disease with a small molecule in a study of mice.
Researchers at the University of Cambridge in Britain found that chemical inhibition, or genetic deregulation of the enzyme N-acetyltransferase 10, improves health and lifespan of people with Hutchinson-Gilford Progeria Syndrome. Their findings were published Friday in the journal Nature Communications.
Patients with the rare condition have an average life expectancy of around 15 years as they develop aging symptoms that include short stature, low body weight, hair loss, skin thickening, problems with fat storage, osteoporosis and cardiovascular disease. They often die of a heart attack.
HGPS occurs in 1 in 4 million newborns worldwide, according to the National Institutes of Health's Genetics Home Reference. Since the condition was first described in 1886, more than 130 cases have been reported in scientific literature.
The disease develops from specific mutations in the gene for the protein Lamin A. A shorter, dysfunctional protein then accumulates in cells, specifically in the membranes surrounding the nucleus. The "packaging" around DNA leads to damage and defective cell proliferation.
"We're very excited by the possibility that drugs targeting NAT10 may, in future, be tested on people suffering from HGPS," senior author Dr. Steve Jackson said in a press release. "I like to describe this approach as a 're-balancing towards the healthy state.' "
Before studies in mice, the authors identified a small molecule called remodelin as an effective ameliorative agent. They then found a component of the cells was being affected by remodelin. It was an enzyme with a variety of cell functions, called NAT10.
"We first studied the cell biology to understand how the disease affects cells, and then used those findings to identify ways to re-balance the defect at the whole-organism level," Jackson said. "Our findings in mice suggest a therapeutic approach to HGPS and other premature ageing diseases."
They used mice with the same genetic defect as HGPS patients to see whether inhibiting NAT10 by chemicals or remodelin or engineering genetically reduced production of NAT10 could dimish the disease.
They were analyzed at 9 and 12 weeks of age.
The tests significantly improved the health of the diseased mice, increased lifespan and reduced HGPS mutation throughout body tissues and at the cellular level, the researchers said.