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Key Points Incomplete understanding of the pathogenesis of Parkinson disease (PD), lack of accurate animal models and validated biomarkers, and limitations in trial design impede the development of effective neuroprotective therapies for PD Novel transgenic animal models, adaptive and delayed-start trial designs, and identification of potential serum, cerebrospinal fluid and neuroimaging biomarkers are facilitating development and testing of effective disease-modifying therapies -Synuclein has a key role in the pathogenesis of PD

Significant potency loss can occur before any visible signs appear

Weight loss itself also triggers biological resistance

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