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Abstract Details

Changes in Brain Activity with Antisense Oligonucleotide RG6042 Treatment in Early Manifest Huntington’s Disease (HD)
Movement Disorders
P5 - Poster Session 5 (8:00 AM-9:00 AM)
3-009

To investigate whether the administration of RG6042, previously known as HTTRx, in individuals with early manifest HD changes brain activity as assessed by resting state electroencephalography (EEG).
EEG measures neuronal activity directly and is known to be altered in HD. Previous analyses of the effects of RG6042, an antisense oligonucleotide targeting huntingtin gene pre-mRNA/mRNA, on a set of predefined EEG features yielded negative results. The EEG data were reanalysed with a data-driven approach, capable of revealing effects not captured by the predefined features.
Forty-six individuals with early manifest HD participated in a randomised, double-blind, multiple-ascending dose, placebo-controlled Phase I/IIa trial of RG6042. Resting state EEG was recorded at baseline and Days 113, 141, 197 post-treatment following the intrathecal injection of four monthly doses of RG6042.

Compared to baseline, RG6042 treatment resulted in an increase in EEG signal power within the 4–8 Hz frequency range, which was reduced in these patients at baseline when compared with healthy controls (HC). The comparison to the placebo group revealed a significant difference between treatment groups, with a decrease of signal power for the placebo group within the same frequency range. This treatment effect was widespread across the scalp. The increase in brain activity with RG6042 treatment was detectable across all dosing levels and was present throughout the duration of the post-treatment EEG monitoring.
RG6042 mediated plastic changes to the EEG that opposed the HD EEG abnormalities and are therefore suggestive of a potential recovery of brain activity. However, other potential reasons for the change in EEG signal are possible and require further investigation. The relationship of these findings to therapeutic benefit await further investigation. EEG signal power at rest may be a critical functional biomarker in HD for monitoring disease progression and therapeutic effects.  
Authors/Disclosures

PRESENTER 		No disclosure on file
No disclosure on file
Amir H. Meghdadi, PhD (Advanced Brain Monitoring) Dr. Meghdadi has received personal compensation for serving as an employee of Advanced Brain Monitoring. The institution of Dr. Meghdadi has received research support from National Institute of Health (NIH).
Shani Waninger, PhD (Advanced Brain Monitoring) No disclosure on file
Anne Smith Anne Smith has received personal compensation for serving as an employee of Ionis Pharmaceuticals. Anne Smith has stock in Ionis Pharmaceuticals.
No disclosure on file
Scott Schobel Scott Schobel has received personal compensation for serving as an employee of F. Hoffman-La Roche Ltd.
No disclosure on file