Biomarker In Alzheimer's Disease - New Report 2009

Main Category: Alzheimer's / Dementia
Also Included In: Pharma Industry / Biotech Industry;  Public Health
Article Date: 29 Jan 2009 - 5:00 PDT

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A new report published by Biopharm Reports in Jan 2009 brings together the latest advances in the identification of biomarkers in Alzheimer's disease. It is hoped that these discoveries will provide new opportunities to tackle this disease, from research through to the clinic. Recent years have seen significant advances in this field and whilst considerable effort has focused on Aβ and tau related markers, a substantial number of other molecules have been identified, that may offer new opportunities.

The last decade has seen important advances in disease biomarkers and is gaining importance in discovery, R&D, diagnostics, therapy and in monitoring patient response to treatment. In most cases, biomarkers are molecules that are linked to the underlying disease and may provide insight from early discovery right through to the clinic. The most important biomarkers allow new tests to be developed which can be used to research, diagnostics and therapy.

Of the many disease areas where biomarkers are important, Alzheimer's Disease (AD) stands out. Despite important advances by scientists in the understanding of AD, much is still unknown in terms of the underlying disease. Biomarkers have an important role to play in helping scientists to unravel the underlying disease mechanism and in guiding physician's in the diagnosis and treating of AD.

Despite its high prevalence, AD is often undiagnosed in its early stages as the first symptoms of the disease, such as forgetfulness, are often misinterpreted as the inevitable consequences of aging. Cognitive tests are used to assess patients suspected of suffering from AD, the gold-standard of which is the ADAS Cog. This is the most advanced cognitive protocol for the assessment of patients; however, a number of simpler tests are also used, including the Mini-Mental State Examination (MMSE) and Mini-Cog.

Despite its importance, ADAS Cog and similar tests present challenges in the assessment of AD symptoms and a study (Connor and Sabbagh J. Alzheimer's Dis. 2008) recently reported on a survey of possible variations in the outcome of ADAS-Cog tests in a clinical trial of 26 volunteer raters using the ADAS Cog. This survey found that the reliability of ADAS-Cog may vary significantly and affect the outcome of clinical studies. The findings have important implication in the tackling of AD, from discovery and clinical R&D, through to treatment in the clinic. With increasing numbers of global clinical trials on AD, the consistent use of such tests is increasingly important in the study of new candidate therapies. Moreover, deficiencies in the assessment of AD underlines the need to develop better tests for the disease and to find reliable biomarkers upon which such tests can be based. This new report, by John Bates PhD (Biopharm Reports) looks at important advances in the discovery of AD biomarkers, their potential in the development of new diagnostics and their integration with current drug development strategies.

Current limitation in the diagnosis and treatment of AD are therefore focussing efforts to identify biomarkers that advance understanding of the disease in both these areas. Research studies are also directed at understanding the pathogenesis of AD, in the hope that therapies can be developed that target and correct the underlying mechanisms. The current development pipeline for AD drugs indicates the emergence of a new era of disease-modifying drugs; advances that it is hoped will be facilitated by recently discovered biomarkers.

The new report identifies 60 candidate AD biomarkers and their associated studies. Of these, 49 are single species or single parameters, 7 are combinations or panels and 4 involve the measurement of two species or parameters or their ratios. These include proteins (n=34), genes (n=11), image-based parameters (n=7), small molecules (n=3), proteins + genes (n=2) and others (n=3). Of these, 30 (50%) relate to species identified in cerebrospinal fluid (CSF) and 19 (32%) were found in the blood. These candidate may be classified on the basis of their diagnostic utility, namely those which i) may allow AD to be detected when the disease has developed (48 of 75†= 64%), ii) may allow early detection of AD (18 of 75† = 24%) and iii) may allow AD to be predicted before the disease has begun to develop (9 of 75†= 12%). † Note: Of these, 11 were linked to two or more of these capabilities (e.g. allowed both early-stage detection as well as diagnosis after the disease has developed).

AD biomarkers identified in this report show significant diversity, however of the 60 described, 18 (30%) are associated with amyloid beta (Aβ) and 9 (15%) relate to Tau. The remainder of the biomarkers (just over half) fall into a number of different groups. Of these, some are associated with other hypotheses on the pathogenesis of AD however the vast majority are individually unique and not obviously linked with other markers. Analysis and discussion presented in this report includes summaries of the studies and clinical trials that have lead to the identification of these markers. Whilst considerable effort has focused on Aβ and tau related biomarkers, a substantial number of other molecules have been identified that may offer new opportunities to tackle AD.

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