SKB discovers Asp 2 Alzheimer's enzyme

Scientists at Philadelphia-based SmithKline Beecham have identified an enzyme that may help drugs target and treat Alzheimer's disease.

"The significance of this discovery is that it offers a new target for drug discovery," said Frank Walsh, vice president and director of Neuroscience Research for SmithKline Beecham. "The goal going forward is to determine whether a compound that inhibits the enzyme will contribute to therapy for Alzheimer's disease."

Alzheimer's disease is associated with a protein fragment called beta amyloid peptide. When this protein is produced in multiple copies that tangle together, it forms structures in the brain known as amyloid plaques. Since this fragment is excised from a longer protein, the existence of enzymes that perform this excision has long been assumed. Two distinct enzymes scissor the precursor proteins at specific points along its length, each enzyme being essential to producing the plaque-forming peptide. Despite the fact that the actual chemical identities of these enzymes have remained unknown, they had been assigned the names gamma-secretase and beta-secretase.

Now, however, SmithKline Beecham scientists have identified an enzyme, which they have called Asp 2, which possesses the essential activities expected of beta-secretase.

Though the discovery of the enzyme is important, Walsh warned against overly high expectations for an Alzheimer's cure at this stage of the finding. "It must be emphasized that much more work is required before anyone can know whether this experimental avenue will lead to a useful pharmaceutical," said Walsh. "Even the role of amyloid plaque, whether it is the cause or merely a consequence of the disease, needs further investigation." PR