A diagnostic assay for a protein associated with Alzheimer'sdisease correctly identified which members of a family wereaffected by a pre-senile stage of the hereditary form of thedisease, according to a study to be published in Saturday'sedition of the British journal The Lancet.

The diagnostic, developed by Sibia Inc. of La Jolla, Calif., isdesigned to measure levels of soluble amyloid beta-precursorprotein (APP) in cerebrospinal fluid (CSF), which bathes thebrain and spinal cord. Lower levels of soluble APP were foundin family members who exhibited symptoms of the disease butwere not yet diagnosed with it.

"The data reported in this study confirm our belief that thelevel of soluble APP in CSF will be useful in the diagnosis ofAlzheimer's disease," said William T. Comer, Sibia's presidentand chief executive officer. "We believe the assay will be thefirst biochemical diagnostic available for a substance known tobe associated with Alzheimer's disease."

An accurate Alzheimer's diagnostic has long been viewed as apotential boon to drug researchers developing potentialtherapeutics to treat Alzheimer's, and may permit an earlierdiagnosis of the disease in patients. Psychological tests are nowused to diagnose the onset of the disease. A diagnosis ofAlzheimer's can be ascertained by an autopsy.

At least a dozen groups of researchers in corporate andacademic laboratories are taking different approaches todeveloping a biochemical diagnostic for Alzheimer's.Commercial developers include American Biogenetic Inc.,Athena Neurosciences Inc., Cephalon Inc. and CortexPharmaceuticals.

Alzheimer's, which afflicts an estimated 4 million Americans, isa degenerative brain disease that is characterized by the build-up of amyloid plaques in brain tissue. One possible explanationfor the disease is that APP is broken down by brain cells in anabnormal way that leaves a protein fragment, Protease NexinII (PN-II), inside the cell. PN-II accumulates into amyloidplaques, which kill neurons, leading to memory loss andeventual death.

Sibia's diagnostic uses a highly specific and sensitivemonoclonal antibody (MAb) to detect the precursor protein,PN-II. However, the complexity of Alzheimer's disease maymean there is more than one diagnostic target, said Steven L.Wagner, Sibia's director of protease development

"People have tried to find a magic bullet marker (forAlzheimer's) for years," he said. "There very well may be moremolecules that need to be monitored."

The data presented in The Lancet support an initial report onSibia's diagnostic published in the April 1 edition of the journalProceedings of the National Academy of Sciences. That studyshowed that Alzheimer's patients showed significantly lowersoluble APP levels than healthy individuals. The new research,which focused on a study of a six-member family with a highincidence of hereditary Alzheimer's, did indicate that thediagnosis might be useful in determining the stage of thedisease's progression.

Sibia said it is moving quickly on plans to market the testthrough clinical reference laboratories, Wagner said. It hasscheduled a second meeting with FDA staff to present itsfindings and to work on a related diagnostic test kit, whichwould require the agency's approval for marketing. Notimetable or price range for a potential product was disclosed.Sibia is also pursuing related therapeutic approaches tointerrupting the production of amyloid plaques.

The company exclusively licensed an underlying patentapplication covering the technology from the University ofCalifornia last September. Sibia is a privately held companyfounded in 1981 by the Salk Institute for Biological Studies.

-- Ray Potter Senior Editor

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