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A Hampel paper for anyone who still doesn't

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XenaLives Member Level  Thursday, 04/18/19 08:21:15 AM
Re: None
Post # of 306907 
A Hampel paper for anyone who still doesn't understand why Anavex is using precision medicine.

Why use a shotgun when you have a rifle?

That's why you use precision medicine.

The following paper is replete with references to other scientific publications but I've edited them out in this section for readability.


Quote:


A PRECISION MEDICINE PARADIGM FOR ALZHEIMER’S DISEASE

The adoption of a PM paradigm for generating innovative strategies to treat, prevent and cure complex diseases is not a novel concept. For decades, the oncology field was at loss as to how to treat patients inevitably dying from advanced late-stage cancer; however, today, mortality and cure rates, at least for some forms of cancer, are far beyond initial expectations. On the other hand, after over 100 years of accumulating scientific knowledge, there is no therapeutic solution for prevention and cure in AD which remains 100% fatal. Available treatments, approved for late potentially irreversible clinical disease stages only, offer marginal clinical benefits. It is time for a paradigm shift, with the field of oncology providing a previously validated model for successful implementation of a PM model that the AD/neurodegeneration field can at least partially adopt .

The concept of PM aims at tailoring medical treatment to the individual genetic drivers, pathophysiological and clinical characteristics of the disease for each single patient15. In other words, it aims at tailoring disease prevention and treatment to the individual’s specific biological makeup (customized treatment), which is in sharp contrast to the ongoing “onedrug-fits-all” approach. Given the highly complex nature of AD, the likelihood of identifying a single drug to provide meaningful benefit to every patient is minimal, at best. This is the situation in other areas such as oncology and cardiology. A key methodological framework required for successfully implementing the PM is the incorporation of the exploratory, integrative, and interdisciplinary systems approach of SB, complemented by systems neurophysiology.

SB allows a system level approach to drug discovery - with special reference to drug target identification, validation, and screening assay development – that embraces the whole complexity of disease pathophysiology. Recent years have witnessed significant success in biomarker-guided therapeutic strategies in advanced translational research fields of biomedicine – including oncology and cardiovascular medicine. The traditional reductionistic categorical nosology of “neurodegenerative diseases” reflects advanced late stages of fragmented clinical phenotypes and syndromes with different or overlapping histopathological patterns. Although continuous working group efforts to refine categorical diagnostic criteria improved the diagnostic reliability and accuracy, particularly after integrating biomarkers as part of the criteria , the validity of current categorical nosological systems for neurodegenerative diseases remains limited. A step in the right direction is represented by the recent formulation of unbiased agnostic biomarker classification systems for AD and neurodegenerative diseases to identify and grade risk in normal elderly people. The goal is to identify the full spectrum of the specific biological alterations in elderly individuals at risk long before the appearance of first clinical symptoms.

We hypothesize that using PM in the fields of Neurology, Psychiatry, and Neuroscience will trigger a paradigm shift in the medical practice of brain diseases towards preclinical detection and effective early interventions. Prevention strategies can be employed before any substantial disease progression has occurred, with a strong focus on individualized care. Among the objectives of PM are to introduce new paradigms for early detection, classification/differential diagnosis, treatment, and prevention of neurodegenerative diseases (better proteinopathies of the brain), based on individual biological differences, as reflected by multimodal biological indicators, biomarkers. In this regard, evolving evidence of AD biomarkers has been obtained during the last 20 years from studies performed in neurogenetics/neuroepigenetics, neurochemistry – the latter having been conducted both on cerebrospinal (CSF) and blood (plasma/serum) – as well as in structural/functional/metabolic neuroimaging, and neurophysiology . Following the oncology model, it is anticipated that innovative biomarker studies, combined with SB, will identify specific diagnostic, prognostic, and predictive biomarker signatures in order to tailor the therapy to individual patients. Additionally, biomarker-guided PM removes today’strial-and-error” strategy to pharmacological interventions, which has significant medical consequences for patients and healthcare system. As stated by the Institute of Medicine (IOM) Committee Recommendations for Advancing Appropriate Use of Biomarker Tests (companion diagnostics) for Molecularly Targeted Therapies, the ultimately goal of PM is to improve both the quality of patient care and clinical outcomes.

In summary, the PM conception is in the process of being applied to AD and across a rapidly increasing number of other neurodegenerative diseases owing to: (I) the development of high-throughput “omic” tools designed for screening biomedical samples and (II) the setting-up of large-scale biological datasets. Consequent development, validation, and implementation of biomarker-guided interventions built on the SB conceptual framework will accelerate the path to PM for AD.





https://hal.inria.fr/hal-01566281/document



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