Rare dwarfism stunts cancer and diabetes; drug trials to follow

A small group in Ecuador almost never gets diabetes or cancer. They’re about three-and-a-half feet tall, and their genetics may hold the key to living a long life for the general population.

For over 20 years, scientists have studied 99 family members from this rare community on the slopes of the Andes, descended from Spanish conversos – Jews who converted to Christianity to avoid the Inquisition.

They carry a mutation in their growth hormone receptor gene (GHR gene), a deficiency called Laron syndrome that stunts their growth. The changes related to their GHR mutation are very similar to genetic changes that make baker’s yeast live long and resistant to toxins.

The finding hints at how inhibiting GHR in people who have reached their adult height could potentially prevent multiple diseases of aging, including cancer and diabetes – diseases that have never killed anyone in this small Ecuadorian population. (One woman developed an ovarian tumor, which was successfully removed.)

In their 1,600 relatives who lack the mutation, cancer caused 20% of deaths, type 2 diabetes caused another 5%.

The researchers analyzed thousands of genes from blood samples from individuals with the GHR mutation and found all kinds of features already known to promote longevity in simpler organisms like yeasts, worms, and rodents: higher insulin sensitivity, lower insulin concentrations, lower amounts of an insulin-like growth factor, and when stressed, their cells tend to self-destruct rather than accumulate DNA damage.

"There was only one major piece missing, which was the human data," says study author Valter Longo of the University of Southern California, "and this is it."

The Food and Drug Administration has already approved drugs that block growth hormone activity in humans – used to treat acromegaly, a condition related to gigantism – such as Pfizer’s Somavert (pegvisomant).

In the next 12 months, Longo hopes to start drug trials on people with high propensities for cancer and diabetes. If successful, a pill to prevent cancer and diabetes could be as common as Lipitor in the prevention of heart disease.

"It's the dream of every administration, anywhere in the world," Longo says. "You live a long healthy life, and then you drop dead."

Artificial blocking isn’t the only way to reduce these hormones. Restricting calories or proteins appear to achieve the same effect; several studies are underway to assess the effect of dietary restriction in humans.

"Nature has given to us an evolutionarily conserved pathway" which, if exploited correctly, may help to prevent diabetes and cancer, says study author Jaime Guevara-Aguirre of Institute of Endocrinology, Metabolism and Reproduction, Quito, Ecuador.

The findings were published in Science Translational Medicine last week.

Images: Members of group in 1988 and 2009 / Jaime Guevara-Aguirre

This post was originally published on Smartplanet.com