Pediatric peptide spurs growth hormone.
Growth-hormone deficiency afflicts about one in every 5,000 infants in the United States. Untreated, these children will grow up to be 7 to 10 inches shorter than normal. Physicians currently treat the deficiency by injecting genetically engineered growth hormone every few days for up to 10 years during a child's critical growth period. But a new drug may someday help many children achieve normal stature by producing the hormone on their own. And in the barnyard, a closely related chemical may yield important dividends of another sort.
About 80 percent of children with the deficiency are physiologically capable of supplying the growth hormone themselves, estimates Arthur Felix, who heads peptide research at Hoffman-La Roche Inc. in Nutley, N.J. What they need are sufficient amounts of the 44-amino-acid peptide that normally triggers the pituitary gland to secrete the hormone. Hoffman-La Roche has now synthesized this peptide, called growth-hormone releasing factor (GHRF).
Felix says GHRF supplementation might offer several advantages over conventional growth-hormone therapy. Containing fewer than one-fourth the amino acids of human growth hormone, GHRF is much simpler to make. Its smaller size also suggests parents may eventually be able to administer it by nasal spray or dermal patch -- techniques children are likely to prefer. Moreover, GHRF treatment would allow the body to generate the whole family of growth-hormone compounds normally secreted, not just the single form provided by hormone therapy today. Finally, the body has a feedback mechanism that will shut off its own GHRF production when growth-hormone levels get too high. This suggests, Felix says, that the body might naturally compensate for any small GHRF overdose, whereas it cannot limit excess growth hormone. Hoffman-La Roche has just begun using the GHRF peptide in a clinical trial expected to involve about 50 children.
The similarity between growth hormone in humans and in many other species led Felix's team to explore livestock applications of the GHRF as well. In a series of just-completed studies, the researchers injected lactating cows and pigs with a 29-amino-acid analog of the pediatric drug's most pharmacologically active region. The shorter anlog not only provided a range of benefits but also proved 5 to 10 times more potent than the 44-amino-acid parent compound. In a 10-day study involving 15 holsteins, those receiving daily injections of the analog produced 15 to 20 percent more milk than did untreated animals. In a 60-day trial involving 75 male pigs, changes were even more striking. Compared with untreated animals, pigs getting the GHRF analog gained 15 percent more weight per pound of feed. The composition of their meat changed, too: They put on 15 percent more muscle and about 25 percent less fat. What's more, says Felix, their meat showed a decline in the ratio of saturated to unsaturated fats.
The team is now working to develop a longer-acting form of the livestock drug, perhaps requiring injection only once every 30 to 60 days. for pediatric use, their eventual goal is a similarly small, high-potency analog.
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Chemistry; growth-hormone releasing factor|
|Date:||Apr 22, 1989|
|Previous Article:||Turning antibodies into chemists.|
|Next Article:||Making plastics visible to X-rays.|