Huntington's Disease and
Parkinson's Disease
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The overall objective of this work is to apply innovative neuroimaging methods sensitive to cerebrospinal fluid (CSF) production, transport, and resorption in patients with Huntington’s disease (HD) and Parkinson's disease (PD) to understand how retention of pathological proteins, such as huntingtin protein or alpha-synuclein, may arise from aberrant neurofluid production or clearance and contribute to symptoms.

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Our manuscripts relevant to this work in Huntington's and Parkinson's disease:

• Reduced cerebrospinal fluid motion in patients with Parkinson's disease revealed by magnetic resonance imaging with low b-value diffusion weighted imaging

• Cerebrospinal Fluid Flow in Patients with Huntington's Disease

• The parasagittal dural space of the human brain

• Dopamine-induced changes to thalamic GABA concentration in impulsive Parkinson disease patients

 

More specifically, promising disease-modifying therapies using intrathecally administered antisense oligonucleotide seek to reduce mutant huntingtin protein expression and offer disease modifying potential in Huntington’s disease. Previous iterations of these interventions have resulted in an increase of neurofilament light protein levels and greater ventricular volumes, but post-hoc data indicates that some patients (younger and earlier in disease stage) may benefit from these interventions. This project aims to improve our understanding of the CSF flow circuit in HD, assess heterogeneity in treatment response, and discover new mechanisms of pathophysiology by assessing production, flow, and absorption of CSF across the stages of HD.

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This work parallels larger sponsor-initiated trials that occur in our center, including but not limited to Enroll-HD. For more information on Huntington's disease trial participation, visit the Huntington's disease center at Vanderbilt, which is a Huntington's Disease Center of Excellence.

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