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Sigma-Aldrich develops Parkinson's disease models

Sigma-Aldrich

Preclinical models/Parkinson's research

Sigma-Aldrich and the Michael J Fox Foundation (MJFF) are collaborating to develop more accurate preclinical research models of Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder of unknown cause that affects nearly five million individuals worldwide.

Under a research grant from MJFF, Sigma Advanced Genetic Engineering (Sage) Labs - an initiative of Sigma-Aldrich's Research Biotech business unit - will use novel CompoZr zinc finger nuclease (ZFN) technology in an effort to create superior preclinical research models critically needed for the development of transformative treatments for Parkinson's disease.

The models, which are expected to take as little as one year to develop, will be made broadly accessible to scientists throughout the Parkinson's research community in order to speed basic research and drug development efforts field-wide.

Although current mammalian models adequately recapitulate some outward symptoms of Parkinson's disease, no existing model has been able to accurately mimic the onset and progression of the underlying disease processes that characterise the disease in humans.

Research already conducted into the genetic causes of Parkinson's disease has identified a number of genes but indicates a strong connection to mutations in five particular genes: LRRRK2, alpha-synuclein, DJ-1, Parkin and Pink1.

MJFF funding will allow Sigma-Aldrich's efforts to create five novel rat models with each of these genes knocked out.

Adopting a new approach to developing more effective and targeted research models, Sage Labs will use the CompoZr ZFN technology in its efforts to design 'knockout' rat models in which the genes known to be directly implicated in Parkinson's disease are omitted.

This research is expected to facilitate the development of new models that scientists believe will provide a better understanding of Parkinson's disease at the molecular, biochemical, physiological and behavioural levels.

This knowledge may, in turn, result in new therapeutic targets and approaches for the treatment of Parkinson's disease.

Because rats are physiologically similar to humans, they are ideal subjects for modelling human diseases and have been an important species for research in a number of fields including physiology, endocrinology, neurology, toxicology and cancer.

Until recently it has been impossible to create rat models with particular genes de-activated, or 'knocked out'.

However, using CompoZr ZFN technology, scientists at Sage Labs are able to generate animal models with targeted genetic changes to better understand gene function and develop new therapeutic approaches.

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