Nancy GarciaAssociate Editor

A privately held Salt Lake City pharmaceutical companyconcentrating on the role of calcium in cells has agreed tosponsor the research of two Harvard Medical School physicians.

"Calcium's role is so ubiquitous in regulating cell function it'sbeen called the universal signal," said Hunter Jackson, chairmanand chief executive officer of NPS Pharmaceuticals Inc.

NPS will collaborate with Edward M. Brown and Steven C.Hebert, associate professors of medicine at Harvard MedicalSchool and physicians at Brigham and Women's Hospital. Thecompany will be able to license any patents that stem from thework of its collaborators, who are interested in the role ofcalcium and calcium receptors in the parathyroid gland and thekidney.

"It is such a new area," Jackson said, "that there really are notother companies that we are aware of that are really involved."A literature search conducted 18 months ago, prior to NPSpublishing a patent in Europe, found no mention of calciumreceptor research.

NPS's director of biology, Ed Nemeth, brought an interest incalcium with him from Case Western Reserve in Cleveland.

The company confirmed the existence of the receptor that hehad previously described, and has developed compounds thatbind to it, derived from a library of plant and animalsubstances.

A small, organic, orally active compound forhyperparathyroidism (HPT) is in preclinical studies and may bethe subject of an investigational new drug (IND) application bythe end of the year. Caused by an excess of parathyroidhormone, the disease may result in kidney stones, osteoporosis,muscular weakness, anorexia or vomiting and drowsiness.

From 60,000 to 100,000 Americans develop primary HPT eachyear. Another 175,000 people have secondary HPT followingrenal failure. There is currently no specific treatment for HPT.

Some people who produce too much parathyroid hormone,which regulates calcium and phosphorus metabolism, show nosymptoms. However, Jackson said, "there is a growingawareness among physicians that there may be insidiousconsequences in renal function, bone loss and hypertension."The mineral is measured in routine blood workups.

Calcium functions as a biological signal via calcium channels innerve cells, receptors inside cells that activate stores of thesubstance, and cellular receptors. NPS hopes to clone thecalcium receptor with its collaborators to probe tissues anddiscover new areas where the receptor is present.

The receptor appears to resemble many others that have beencharacterized, although it is the only receptor for an atom thatthe company is aware of having been described.

Besides parathyroid cells, NPS has found evidence of calciumreceptors in cells that govern the resorption of bone. Thesebone-dissolving osteoclasts work in concert with bone-secreting osteoblasts to constantly remodel bones. But in aging,the balance tilts toward resorption and leads to the weakenedbones seen in osteoporosis.

Other calcium receptors are apparently present on cells thatsecrete calcitonin, which supresses the resorption of bone andhas been used to treat osteoporosis. Osteoporosis is a likelytherapeutic target, since calcitonin is hard to administer, andthe calcium receptor could provide access to the cells thatsecrete this major physiological regulator that is principallyresponsible for bone resorption, Jackson said.

The Harvard collaborators are interested in kidney tissue,where cells responsible for calcium asorption could provide anapproach to controlling hypertension by controlling thesecretion of renin. Another possible therapeutic target isstroke.

"I think the commercial importance of this will be very great,"Jackson said.

(c) 1997 American Health Consultants. All rights reserved.

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