Hutchinson-Gilford progeria syndrome in children may be helped by cancer drugs

Aug 31 2005

Children who suffer from a rare disease called progeria, which accelerates aging and often kills patients when they are in their teens, may possibly be helped by drugs being developed to treat cancer.

Researchers in the U.S. have found that a group of drugs known as farnesyltransferase inhibitors or FTIs could restore the normal shape of cells damaged by Hutchinson-Gilford progeria syndrome or HGPS.

According to two separate reports, the researchers say the drugs are already being tested in children and appear to be safe.

Stephen Young of the University of California Los Angeles, who led the first study, has apparently said they are presently conducting experiments in animals to check the drugs do work.

His team is also testing other types of drugs, but says the findings so far could help lead to treatments for progeria and perhaps related disorders, including osteoporosis and hardening of the arteries but also rare conditions caused by similar processes.

It seems that one in 4 million children are born with progeria, which causes dramatically accelerated aging and early heart disease.

The children become wizened, lose their hair, develop wrinkles and thin bones, and usually die from hardened arteries before they reach 15.

Progeria syndrome is caused by mutations in the gene for a protein called lamin A, which is important for normal cell function.

This "bad" protein deforms the nucleus, causing miscommunications with other cells.

Young's team have discovered that the farnesyltransferase inhibitors corrected this deformity in mice bred to develop a disease similar to progeria.

The researchers say they have confirmed their findings in cells taken from children with progeria.

Apparently a second team at the National Human Genome Research Institute, the Howard Hughes Medical Institute and elsewhere, have also made similar findings.

NHGRI director Dr. Francis Collins has said that although FTIs were originally developed for cancer, they are capable of reversing the dramatic nuclear structure abnormalities that are the hallmark of cells from children with progeria.

Collins says the discovery is "a stunning surprise", and compares it to finding out that the key to your house also works in the ignition of your car.

He says it might also be possible that the drugs, or similar drugs, could affect normal aging, and says they are exploring the possibility that FTIs might also slow down the aging process in normal cell cultures.

At present two FTIs are in phase III clinical testing, the last stage before U.S. Food and Drug Administration approval is sought.

One is called lonafarnib and is made by Schering-Plough, and the other called tipifarnib is made by Johnson & Johnson.

Young says other approaches, including newer therapies called antisense and RNA interference, which directly affect the genetic defects as opposed to interfering with the faulty protein, might also work.

Young's team have also found that an osteoporosis drug called alendronate may help treat progeria by interfering with the faulty protein, and as yet unpublished experiments have shown it also improves the misshapen nucleus.

Although the drugs are thought to be very safe, Young says it is too early to test such drugs in progeria patients.

The reports are published in the Proceedings of the National Academy of Sciences.