Motor symptoms are core feature of HD, important in establishing the clinical diagnosis and contributing to disability. The motor WG aims at:
- Teaching clinicians about the different presentations of motor symptoms and their possible treatments, pharmacologic and non-pharmacologic (e.g. physiotherapy).
- Standardizing the clinical motor assessment of HD patients by providing quality assurance tools such as the annual UHDRS-TMS online certification (see below).
- Foster the development of novel more reliable and sensitive endpoints for clinical trials by exploring quantitative motor (e.g., “Q-Motor”*) assessments in biomarker studies and clinical trials (see below). This work is conducted to explore whether placebo effects observed in clinical trials can be reduced, whether sensitivity can be extended to prodromal, premanifest cohorts, and whether quantitative measures may help to facilitate data driven decisions in adaptive clinical trial designs to reduce burden of patients and increase chances of success in clinical development.
UHDRS-TMS Online Certification and Teaching Video:
The Motor WG established an annual online certification for clinicians active in clinical trials in HD (PI: Ralf Reilmann, funded by CHDI). This certification is provided since 2008 and established international standard. Certification is required for raters in ENROLL-HD and clinical trials globally. A teaching video provides instructions on how to perform and rate the UHDRS-TMS with samples for each stage of disability (Reilmann et al., 2009;Reilmann and Schubert, 2017a).
We work on improving and revising the UHDRS-TMS, the standard clinical motor assessment scale applied in clinical trials Siesling et al., 1997;Siesling et al., 1998). Current projects use the data generated from the UHDRS-TMS certification (work ongoing). We aim to (1.) avoid redundant items to reduce the burden of the assessments, (2.) to explore novel assessments that may be more sensitive to early changes, and (3.) to explore subsets of items that may be less affected by placebo-effects.
We develop and assess novel and objective motor endpoints for clinical trials, e.g. the Q-Motor assessments, which were developed in TRACK-HD and applied in the clinical trials, e.g. PRIDE-HD, AMARYLLIS, LEGATO-HD, SIGNAL and others (Bechtel et al., 2010;Reilmann et al., 2015;Reilmann et al., 2017;Reilmann and Schubert, 2017b). Novel assessments are being tested in several projects, e.g. REPAIR-HD (www.repair-hd.eu). We will look at the performance of these measures in comparison to the UHDRS-TMS and other clinical measures in biomarker studies and particularly in the clinical trials these measures were used in.
Effects of Motor interventions:
In collaboration with the Physiotherapy WG the Motor WG aims to assess efficacy of motor therapies such as physiotherapy or exercise in clinical studies (Quinn et al., 2016). A novel international multicentre randomized trial using Q-Motor as exploratory endpoint is ongoing (PACE-HD) funded by the Gossweiler Foundation (www.jggf.ch).
* Conflicts of Interest Disclosure: Dr. Ralf Reilmann holds patents for Q-Motor assessments and is founding director and owner of QuantiMedis GmbH, a for-profit company providing Q-Motor services for instance in clinical trials. QuantiMedis GmbH has received payments for Q-Motor assessments from BMBF, CHDI, DFG, DZNE, EU-FP7, Ipsen, Lundbeck, Novartis, Pfizer, Teva, Vaccinex, and uniQure.