Limits...
New animal models of progressive neurodegeneration: tools for identifying targets in predictive diagnostics and presymptomatic treatment.

Tasker RA, Adams-Marriott AL, Shaw CA - EPMA J (2010)

Bottom Line: Many of these diseases and disorders are characterized by progressive deterioration over time, that ultimately results in identifiable symptoms that in turn dictate therapy.A better understanding of presymptomatic events could allow for the development of new diagnostics and earlier interventions that could slow or stop the disease process.Such studies of progressive neurodegeneration require the use of animal models that are characterized by delayed or slowly developing disease phenotype(s).

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PEI, Canada C1A4P3.

ABSTRACT
Mental and neurological disorders are increasingly prevalent and constitute a major societal and economic burden worldwide. Many of these diseases and disorders are characterized by progressive deterioration over time, that ultimately results in identifiable symptoms that in turn dictate therapy. Disease-specific symptoms, however, often occur late in the degenerative process. A better understanding of presymptomatic events could allow for the development of new diagnostics and earlier interventions that could slow or stop the disease process. Such studies of progressive neurodegeneration require the use of animal models that are characterized by delayed or slowly developing disease phenotype(s). This brief review describes several examples of such animal models that have recently been developed with relevance to various neurological diseases and disorders, and delineates the potential of such models to aid in predictive diagnosis, early intervention and disease prevention.

No MeSH data available.


Related in: MedlinePlus

Representation of the concept of progressive neurodegeneration and presymptomatic therapeutic intervention. Events, often unidentified, initiate a progressive deterioration of brain health that continues for some time prior to the appearance of symptoms associated with a particular neurological disease. Traditionally therapy is initiated at the time of symptom onset and diagnosis, but earlier detection of deteriorating brain health would allow for presymptomatic intervention that could slow or prevent disease progression
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3405326&req=5

Fig2: Representation of the concept of progressive neurodegeneration and presymptomatic therapeutic intervention. Events, often unidentified, initiate a progressive deterioration of brain health that continues for some time prior to the appearance of symptoms associated with a particular neurological disease. Traditionally therapy is initiated at the time of symptom onset and diagnosis, but earlier detection of deteriorating brain health would allow for presymptomatic intervention that could slow or prevent disease progression

Mentions: Symptoms of many forms of progressive disease often appear in late adolescence or early adulthood and then become increasingly severe with increasing age. The neurodegenerative process however, usually begins long before the onset of clinically diagnosed symptoms. For example, it is estimated that up to 60% of the dopaminergic neurons in the substantia nigra need to be lost before the first clinical signs of Parkinson’s disease appear [3]. Thus, in many cases a precipitating event occurring much earlier in life, often around the time of birth or in early childhood, appears to initiate a degenerative cascade that proceeds undetected for some time prior to the onset of clinical signs. Presymptomatic detection of disease represents, therefore, a largely unexplored opportunity for therapeutic intervention. By detecting the disease process earlier, and initiating appropriate therapy to arrest the neurodegenerative process prior to the onset of symptoms, the disease process could be slowed or even stopped long before the patient becomes debilitated by both the primary disease process and secondary complications. This general concept is depicted in Fig. 2. While conceptually simple, such an approach to preventative therapy is by no means easy to implement. Even if pre-symptomatic biomarkers relevant to individual diseases could be identified, health budgets can not possibly support sustainable screening of all members of the population, and the incidence of these diseases is too large to permit accurate presymptomatic risk analysis (eg. Framingham). Further, most neurological diseases are presumed to not result from a single precipitating event, but rather arise from a complex interaction between initiating stimuli, genetic predisposition, environmental factors and lifestyle [4]. None-the-less, the overall goal of identifying disease earlier is both socially and economically responsible and should be vigourously pursued. Genetic predispositions and gene-environment interactions can be identified for individual diseases through careful study, and it is quite conceivable that the early indicators of neurodegeneration may be common or overlap between different diseases. This latter point gives rise to hope, and is supported by the knowledge that many neurodegenerative diseases demonstrate co-morbidity. In other words patients with a diagnosis of one disease often show signs of others. For example schizophrenia patients often suffer from epilepsy, Parkinson’s disease patients often develop dementia, and epilepsy patients often present with cognitive impairment. Thus, while the ultimate diagnosis of disease reflects the predominant symptomatology (which in turn dictates treatment), it is reasonable to assume that disease phenotypes overlap to some extent and may, therefore, have some common origin(s).Fig. 2


New animal models of progressive neurodegeneration: tools for identifying targets in predictive diagnostics and presymptomatic treatment.

Tasker RA, Adams-Marriott AL, Shaw CA - EPMA J (2010)

Representation of the concept of progressive neurodegeneration and presymptomatic therapeutic intervention. Events, often unidentified, initiate a progressive deterioration of brain health that continues for some time prior to the appearance of symptoms associated with a particular neurological disease. Traditionally therapy is initiated at the time of symptom onset and diagnosis, but earlier detection of deteriorating brain health would allow for presymptomatic intervention that could slow or prevent disease progression
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3405326&req=5

Fig2: Representation of the concept of progressive neurodegeneration and presymptomatic therapeutic intervention. Events, often unidentified, initiate a progressive deterioration of brain health that continues for some time prior to the appearance of symptoms associated with a particular neurological disease. Traditionally therapy is initiated at the time of symptom onset and diagnosis, but earlier detection of deteriorating brain health would allow for presymptomatic intervention that could slow or prevent disease progression
Mentions: Symptoms of many forms of progressive disease often appear in late adolescence or early adulthood and then become increasingly severe with increasing age. The neurodegenerative process however, usually begins long before the onset of clinically diagnosed symptoms. For example, it is estimated that up to 60% of the dopaminergic neurons in the substantia nigra need to be lost before the first clinical signs of Parkinson’s disease appear [3]. Thus, in many cases a precipitating event occurring much earlier in life, often around the time of birth or in early childhood, appears to initiate a degenerative cascade that proceeds undetected for some time prior to the onset of clinical signs. Presymptomatic detection of disease represents, therefore, a largely unexplored opportunity for therapeutic intervention. By detecting the disease process earlier, and initiating appropriate therapy to arrest the neurodegenerative process prior to the onset of symptoms, the disease process could be slowed or even stopped long before the patient becomes debilitated by both the primary disease process and secondary complications. This general concept is depicted in Fig. 2. While conceptually simple, such an approach to preventative therapy is by no means easy to implement. Even if pre-symptomatic biomarkers relevant to individual diseases could be identified, health budgets can not possibly support sustainable screening of all members of the population, and the incidence of these diseases is too large to permit accurate presymptomatic risk analysis (eg. Framingham). Further, most neurological diseases are presumed to not result from a single precipitating event, but rather arise from a complex interaction between initiating stimuli, genetic predisposition, environmental factors and lifestyle [4]. None-the-less, the overall goal of identifying disease earlier is both socially and economically responsible and should be vigourously pursued. Genetic predispositions and gene-environment interactions can be identified for individual diseases through careful study, and it is quite conceivable that the early indicators of neurodegeneration may be common or overlap between different diseases. This latter point gives rise to hope, and is supported by the knowledge that many neurodegenerative diseases demonstrate co-morbidity. In other words patients with a diagnosis of one disease often show signs of others. For example schizophrenia patients often suffer from epilepsy, Parkinson’s disease patients often develop dementia, and epilepsy patients often present with cognitive impairment. Thus, while the ultimate diagnosis of disease reflects the predominant symptomatology (which in turn dictates treatment), it is reasonable to assume that disease phenotypes overlap to some extent and may, therefore, have some common origin(s).Fig. 2

Bottom Line: Many of these diseases and disorders are characterized by progressive deterioration over time, that ultimately results in identifiable symptoms that in turn dictate therapy.A better understanding of presymptomatic events could allow for the development of new diagnostics and earlier interventions that could slow or stop the disease process.Such studies of progressive neurodegeneration require the use of animal models that are characterized by delayed or slowly developing disease phenotype(s).

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PEI, Canada C1A4P3.

ABSTRACT
Mental and neurological disorders are increasingly prevalent and constitute a major societal and economic burden worldwide. Many of these diseases and disorders are characterized by progressive deterioration over time, that ultimately results in identifiable symptoms that in turn dictate therapy. Disease-specific symptoms, however, often occur late in the degenerative process. A better understanding of presymptomatic events could allow for the development of new diagnostics and earlier interventions that could slow or stop the disease process. Such studies of progressive neurodegeneration require the use of animal models that are characterized by delayed or slowly developing disease phenotype(s). This brief review describes several examples of such animal models that have recently been developed with relevance to various neurological diseases and disorders, and delineates the potential of such models to aid in predictive diagnosis, early intervention and disease prevention.

No MeSH data available.


Related in: MedlinePlus