Abstract Details

Title Tracking Longitudinal Change In Presymptomatic Genetic Prion Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S28 - Vascular and Other Non-Alzheimer’s Dementias (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Objective

Identify potential biomarkers for future treatment trials in the presymptomatic phase of genetic prion disease (gPrD).

Background

By the time patients with gPrD become symptomatic, potential treatments are unlikely to have benefit. Approximately 15% of human PrDs are genetic, caused by PRNP mutation. As a simple genetic test can identify mutation carriers from gPrD families before symptom onset (presymptomatic), this group is an ideal target for therapeutic trials to delay or prevent onset. To prepare for upcoming trials, we need biomarkers of the earliest changes prior to symptom onset.

Design/Methods Our preliminary data suggested we can measure such biological changes in presymptomatic gPrDs. Without formal funding, we evaluated ~110 participants, following them in an ad hoc manner (less than annually) since 2002. After obtaining NIH R56/R01 funding in 9/2018, we are assessing carriers and non-carrier family members approximately annually using a standardized assessment battery over a 2-day visit.

Results Approximately 196 gPrD participants from 73 families involving 20 PRNP mutations had research visits from 3/2002-8/2023, including 50 presymptomatic gPrD participants seen through our NIH grant who are from 29 families representing 6 common high penetrance PRNP mutations. 70% (of the 50) are carriers, 30% are non-carrier controls. These 50 had 92 visits prior to and during the NIH grant, with 26/50 participants having serial research visits, some prior to the NIH funding period. Participants have the following assessments: 3T MRI, neuropsychological testing, CSF, blood (for DNA, plasma, serum, RNA), genetic counseling, detailed history and neurological exam, informant measures, quantitative motor testing (qMotor), OCTs, skin biopsies (began 2022), and some had home sleep assessments. Recruitment continues.

Conclusions Long-term observational studies in presymptomatic gPrD are feasible. Serial evaluations are continuing, and we expect we will identify potential biomarkers of change over the course of presymptomatic gPrD, providing key data for future trials.

Authors/Disclosures
Michael D. Geschwind, MD, PhD, FAAN (UCSF) PRESENTER	Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Brainstorm Cell Therapeutics, Inc.. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Walter Grubb. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lehrman Group. Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Reata Pharmaceuticals, Inc..
Guoyu Zhou	No disclosure on file
Theresa Driscoll (Ucsf)	No disclosure on file
Supratik Nandi (UCSF Memory and Aging Center)	No disclosure on file
Kolette Cho	No disclosure on file
Michael Terranova (UCSF DR. MICHAEL GESCHWIND)	Michael Terranova has nothing to disclose.
Kelly Goodman-O'Leary	No disclosure on file
Stacy Metcalf	No disclosure on file
Megan Casey	No disclosure on file
Sven Forner	No disclosure on file
Robin Schubert	No disclosure on file
Ralf Reilmann, MD, FAAN (George-Huntington-Institute)	The institution of Dr. Reilmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Reilmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for uniQure. The institution of Dr. Reilmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for WAVE. Dr. Reilmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for WAVE. The institution of Dr. Reilmann has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for IOS-Press. The institution of Dr. Reilmann has received research support from European Union. Dr. Reilmann has a non-compensated relationship as a Executive Committee Member with Huntington Study Group that is relevant to AAN interests or activities. Dr. Reilmann has a non-compensated relationship as a Member of Executive Committee with European Huntington Disease Network that is relevant to AAN interests or activities. Dr. Reilmann has a non-compensated relationship as a Co-Chair Task Force on Huntington Disease with Movement Disorders Socitey that is relevant to AAN interests or activities.
Amy Kuo	No disclosure on file
Kendra Benisano	No disclosure on file
Aili Golubjatnikov	No disclosure on file
Katherine Wong, MD (University of Southern California)	Dr. Wong has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for various law firms. Dr. Wong has stock in Biogen.

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