Children afflicted with accelerated aging or progeria do not live beyond their teens, usually dying from heart disease or stroke. In the absence of specific treatment for progeria, development of drugs that inhibit the enzymes underlying the premature and accelerated aging could potentially be an elixir of life.
Accelerated aging or progeria is a rare childhood condition with symptoms strongly akin to normal human aging. Progeria symptoms include:
- Growth failure during the first year of life
- Narrow, shrunken or wrinkled face
- Baldness
- Missing eyebrows and eyelashes
- Stunted stature
- Big head and small face
- Open soft spot
- Small jaw
- Dry, scaly, thin skin
- Restricted range of motion
- Delayed or absent teeth
The classical form of progeria, called Hutchinson-Gilford Progeria Syndrome (HGPS), is attributed to a spontaneous mutation that is not inherited from the parents. The mutation occurs in the protein called prelamin A, leading to its excessive accumulation in the membrane surrounding the nucleus. The enzyme, called ICMT (isoprenylcysteine carboxyl methyltransferase) is to blame as it chemically modifies the prelamin A protein.
The key to successfully preventing the mayhem, therefore, is to block the ICMT, thereby preventing the attachment of the chemical group to prelamin A and significantly reducing the ability of the mutant protein to induce progeria.
Drugs that block the specific enzyme may be useful in treating progeria. Researchers led by Martin Bergö, Professor at the Sahlgrenska Academy, University of Gothenburg and research director at the Sahlgrenska Cancer Center, report in the journal Science, that the development of progeria in mice could be blocked by reducing the production of this enzyme. The results indicate that blocking the ICMT enzyme increased body weight, normalized grip strength, and prevented bone fractures and death in the experimental mice.
"This study is a breakthrough for our research group after years of work. When we reduce the production of the enzyme in mice, the development of all the clinical symptoms of progeria is reduced or blocked. We have also studied cultured cells from children with progeria, and can see that when the enzyme is inhibited, the growth of the cells increases by the same mechanism as in mouse cells," says Martin Bergö, in a press release.
"We are collaborating with a group in Singapore that has developed candidate ICMT inhibitor drugs and we will now test them on mice with progeria. Because the drugs have not yet been tested in humans, it will be a few years before we know whether these drugs will be appropriate for the treatment of progeria," Martin Bergö explains.
"The reason is obvious: the resemblance between progeria patients and normally-aged individuals is striking and it is tempting to speculate that progeria is a window into our normal aging process. The children develop osteoporosis, myocardial infarction, stroke, and muscle weakness. They display poor growth and lose their hair, but interestingly, they do not develop dementia or cancer," says Martin Bergö. The research has implications for aging, and understandably, the scientists are also studying the impact of inhibiting ICMT on the normal aging process in mice.
