|
The Hope for a cure for kids with progeria may have
a fringe benefit: It could extend all human life as well
Wales, Florida. Five-year-old Jesus
Piedra. from Mexico,
has his eyes on one of the golf carts that tool around the grounds of the
ranch. “Could I drive it?" he asks his father in Spanish. “You drive, and
I'll sit behind you and help,” his father agrees. Then the idea is translated
into English for some of the other children. “Can I come. too?” says Courtney
Arciaga, a fiveyear-old from Bonita Cal-ifornia. “But after horseback riding?”
There are 16 children in all, Sitting with their parents, making similar
plans. The kids, who come from seven different countries, range in age
from three to 19: and. based only on their interests, demeanor and liveliness, they seem much like
any other group By Herbert Burkholz of kids on vacation. They are. howev-er,
very different. They look like little old men and women. Their faces are pinched and withered, their heads are bald, they have
wrinkled skin, stiff joints and atherosclerosis, and all of them suffer
from severe cardiovascu-lar problems. They are victims of the condition
called progeria.
Taken from the Greek for “prematurely old,” progeria
is a rare genetic disease that appears to accelerate the child from infancy
to old age, and then to death. within a few short years. The average age
at death is 13, the usual cause a heart attack or stroke. Until recently,
there was no help for these children, much less a cure. But an advance
in the use of human growth hormone has opened up a window to the future
for progeria children.
No one is claiming a cure yet, but for the first
time there is a glimmer of hope, and along with that hope have come new insights
into the process of aging itself. For those who study ag-ing, the same
research that may sorne-day give progeria children a better and longer
life may also lead to a means of extending human life in general.
Progeria was first described in 1886 by Drs. Jonathan
Hutchinson and Hast-ings Gilford. and since that time there have been roughly
100 cases reported around the world. The condition is extremely rare. There
are fewer than 20 known progeria children alive to-day,
and for the past nine years the Sunshine Foundation,
a philanthropic organization. has gathered them togeth-er for a week of
fun. The gathering has two purposes: It allows the children to mingle for
a while with their only true peers. and it allows the physicians who specialize
in the field to examine the children in one place and monitor their condition.
“There are tears through the whole week,” says Sue
Arciaga.
Courtney’s mother. “The last hour is a real emo tional time because you’re
not sure who is going to come back next year. You just hug and hug so tight,
and hope that they’re going to come back.”This year the physicians at the
gathering are W. Ted Brown, M.D., Ph.D.. chief of the division
of human genetics at the North Shore HospitaL Cornell University Medical
College in Manhasset, New York. and Franklin DeBusk, M.D., a teaching pediatrician
at the University of Florida College of Medicine in Gainesville.
Watching
the children play, DeBusk makes the point that pro-geria is not an exact
model of the ag-ing process. “The children have no old-age mental problems.”
he says, “nor do they have the usual eye and ear ailments that come with
aging. They don’t get old-age arthritis, and they don’t have a consistent
problem withblood lipids or cholesterol.”Despite this, Brown and DeBusk
agree that if progeria is not an exact model of aging, it is an excellent
working model, the best available. and nothing proves the point better
than what they call the hyaluronic acid factor.
Hyalurorvc acid
is a molecule found in the connective tissues of animals. Though the acid’s
function is not completely understood, in limited experiments the progeria
children have been shown to excrete more than ten times the normal amount
for their age. Similarly limited tests show that the excretion level of hyaluronic
acid in normal people increases with age-and the levels excreted in the progeria children are higher even
than those found in the elderly.
From this follows the
theory that 1)
an excess output of hyaluron-ic acid may be a normal characteristic of
aging that occurs in progeria at an accelerated rate, and 2) that the disease
may be caused by a cell defect that prevents the normal regulation of hyaluronic
acid in the body. “Our assumption is that this defect has a genetic origin,”
Brown explains, “just as aging has a genetic component. We feel that these
kids are born with a mutated gene that’s involved in the longevity process,
and our goal is to determine what that gene is.”
THE MIRACLE OF HUMAN GROWTH HORMONE
Pinpointing the gene, however. is a long-term goal. More
immediately, there is the work with the rapidly aging kids-like little
Jessica Davis, from Scottdale. Pennsylvania. The daughter of Donald and
Rachel Davis, Jessica weighed a conventional six pounds, ten ounces at
birth, and like all progeria children she displayed no signs of abnormality
then. But her weight and growth soon leveled off, and today, at the age
of six, she weighs only 18 pounds and stands 31 inches tall. Her features
are birdlike, her skin is paper thin, she: wears a frilly bonnet to conceal
her baldness and she has already suffered several mild strokes. But despite
her appearance, she is brash. bright and witty, shows all the enthusiasms
of a typical six-year-old and dreams of be-ing a ballerina someday.
The Davises were reluctant, at first, to have their daughter
used as the sub-ject of a scientific experiment, for they guard her privacy
fiercely. This is an attitude common to all progeria par-ents. one of many
that they share. Since there are so few of them. and since they are all
in the same boat, they often feel closer to each other than to members
of their own families. “Everyone here [in Florida] seems like part of your
family,” explains R.C. Ar-ciaga. Courtney’s father “As soon as something
happens to one of the other families, we all know about It It’s like a
little chain-everyone calls one anoth-er” Last June, despite the desire
to keep her out of the spotlight. Jessica became the second progeria child
to be treated with a genetically engi-neered version of the human growth
hormone.
In its natural state, this hormone is secreted in the
pituitary gland at the base of the brain. and it stimulates the production
of a com-pound called insulinlike growth factor-1 (IGF-1), a protein that
promotes tis-sue growth and organ health. Until re- cently, the only source
of the hormone was human cadavers, which severely limited its use, but
in 1980 genetic engi-nears at both Eli Lilly & Co. and Genen-Kids suffering
from progeria are like living laboratories of the aging process tech Inc.
perfected a method for producing a recombinant form of the hormone, thus
making it available to researchers. By then, progeria specialists were
aware that the growth-hormone levels in children with the condition were
nor-mal for their age. but that their IGF-1 levels were extremely low.
The normal level of growth hormone should
stimu-late the
production of an equally nor-mal level of IGF-1, and the inescapa-ble conclusion
was that the growth hormone in the children somehow was not able to do
its job. Since the natural hormone was not working to produce IGF-1. Fima
Lif-shitz M.D.. chief of North Shore Hos-pital’s division of pediatric
endocrinol-ogy, metabolism and nutrition, and his colleagues decided to
try the man-made version on the children. They were looking for more than
its known ability to treat short stature, hoping that it would increase
the IGF-1 level, and that IGF-1 would have other bene-ficial effects on
the children’s bodies, particularly their metabolism. “These children have
a very high met-abolic rate,” Brown explains, “and . that’s most unusual,
not seen except in children who are hyperthyroid. Jes-sica, for example,
burns up her fat stores at double the normal rate.”
The first child to receive the
treat-ment was four-year-old
Kevin Brown (no relation to the physician) of Elyria. Ohio. The treatment
began in November 1969. and the results were soon obvi-ous, Kevin’s metabolic
rate began to fall, his IGF-1 level began to rise and, most dramatically,
he grew an inch and a half in six months, as compared to the half inch
annually that is typical of progeria children (an inch for normal kids).
He also began to grow hair and gain weight, and at his next examina-tion.
the physicians will look for chang-es in the ratio of his muscle mass to
fat. an indication of whether his inter-nal organs are now aging less rapidly.
(With age, fat tends to accumulate around internal organs.) The attitude
among the researchers has been one of professionally guarded optimism.
but Brown, who is overseeing Kevin’s treat-ment, clearly believes that
he is on the right track. It was alter the results with Kevin that Jessica’s
parents agreed to have her join the program, for if Brown is right, then
a treatment and maybe, ultimately, a cure for progeria is in sight for
the first time.
REVERSING THE AGING PROCESS
This guarded optimism turned to gen-uine excitement last
summer when The New England Journal of Medicine pub-lished a study on the
use of growth hormone at the other end of the age spectrum. After a clinical
test of 21 men with low IGF-1 levels, ranging in age from 61 years to 61
years, Daniel Rudman, M.D., and colleagues at the Medical College of Wisconsin
in Milwaukee determined that treatment with the recombinant version of
the growth hormone could at least temporarily reverse many of the effects
of aging in the body.
In the study, regular injections of the hormone substantially
reduced the excessive fat tissue and the atrophying of muscles that are commonly found in elderly men. The
subjects came out of the program with leaner bodies and stronger skin and spines. By many standards. their
apparent
age had dropped by 20 years. The experiment had been designed to test the
theory that much of the frailty of aging comes from a drop in the production
of the natural growth hormone in the body, which tends to decline after
age 30. and by age 60 may be reduced by as much as 60 percent. In the study,
the man-made equivalent appeared to compensate for that loss. and to restimulate
the release of IGF-1. thus promoting tissue growth.
After six months of
treatment, the skin of the men involved had regained a youthful thickness;
and although there had been no overall weight loss. they had averaged an
6.6 percent increase in lean tissue and a 14.4 percent drop in fat tissue.
Much of the added bulk had arisen in the muscles, while the rest had helped
to rebuild such vital or-gans as the heart, the kidneys and the gastrointestinal
tract. Although the study involved only men. Rudman believes the treatments
were likely to have the same effect on women. “It’s exciting news,” Brown
says. “They’ve clearly shown there is some relationship between the growth
hormone we’ve been using on the kids and the aging process in general.”
|
