In search of biomarkers

摘要

This commentary starts from my frustration that no new drugs to combat Alzheimer's disease have been approved by the US Food and Drug Administration (FDA) since 2003. The few medications currently available address the symptoms of cognitive loss, but they do not delay or modify disease progression, and they work for only a limited time. In some people, they offer no relief at all. It can take more than 10 years and almost US$2 billion to bring a new drug into clinical use. Failure rates are high, especially for drugs that target the brain. And research into Alzheimer's disease is still stuck on a fundamental question. Although abnormal brain deposits of two proteins - amyloid-|3 and tau - are hallmarks of the disease, we do not know if they are a cause or a by-product of the disorder. Some Alzheimer's researchers believe that recently tested drugs might have failed because they were evaluated in people in the later stages of disease, when irreversible damage had already occurred and removing amyloid-(3 was no longer beneficial. To modify disease progression, therapies need to be applied earlier and be targeted at the disease mechanisms occurring in the brain at that stage. We therefore need better biomarkers to provide insight into disease progression and to help target drugs to the right pathological processes at the right time. We are making strides. This year, the National Institute on Aging (NIA), which is part of the US National Institutes of Health (NIH), and the Alzheimer's Association jointly introduced a different way of thinking about Alzheimer's disease. These new diagnostic guidelines - the first in 27 years - should not only guide research but also enhance the development and testing of interventions. They present three stages of Alzheimer's disease: preclinical1, mild cognitive impairment2 (MCI), and dementia3.