At the AD/PD 2025 International Conference on Alzheimer’s and Parkinson’s Diseases, Roche outlined the effectiveness of digital health technologies (DHTs) in providing more sensitive measures of disease progression in early Parkinson’s disease (PD). There are no pathological or imaging-based biomarkers to measure a PD patient’s progression. Instead, physicians rely on clinical examinations and obtaining a history of symptoms. DHTs are poised to help bolster the density of outcome data in PD clinical trials. This supports insights from key opinion leaders (KOLs) previously interviewed by GlobalData, who noted the need for more effective measures in PD clinical trials.
PD is a complex, multi-system, neurodegenerative disorder that affects movement control. It is characterised by progressive degeneration of the dopaminergic neurons of the substantia nigra pars compacta (SNpc), which reduces the levels of dopamine available for neurotransmission in the corpus striatum. The biochemical imbalance manifests as an inability to control body movements and disability that progressively worsens over time. There are several challenges in measuring disease progression in PD. This includes the fluctuating nature of the disease and the high variability in progression rates in PD patients. Due to the fluctuating symptoms, it can be difficult for investigators to capture the effect of an investigational drug through traditional methods of assessment during infrequent clinic visits, where physicians see only a small portion of the larger range of motor fluctuations. DHTs can measure symptom fluctuations and variability frequently and remotely, allowing them to be quantified and aggregated. This can help build more robust outcome measures in PD clinical trials, allowing for the development of more effective agents. The progression of PD as measured on clinical scales, such as the Hoehn and Yahr (HY) scale and the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), is slow. This has implications for the costs and duration of clinical trials measuring early PD agents, as the trials will have to be run for longer to discern the effectiveness of pipeline treatments. Furthermore, anti-parkinsonian medications such as monoamine oxidase B (MAO-B) inhibitors and dopamine agonists (DAs) affect all cardinal signs of PD. As such, it is difficult to measure disease progression with traditional measures. DHTs can aid investigators by bolstering sensitivity to disease progression, even when PD patients are under symptomatic treatment.
In the E-Poster presented at AD/PD, Roche investigated the potential of DHTs to measure disease progression in a subset of patients with early PD under stable symptomatic treatment who were enrolled either in the PASADENA trial (NCT03100149) or the McGill observational study. The PASADENA trial implemented a smartwatch, which was used by patients to passively measure aspects of motor function such as mobility and gait. The watch, coupled with Roche’s PD Mobile Application v2 smartphone application, actively measured motor function through targeted tests. Within Roche’s mobile application, ten motor active tests measure the key neurobiological components of PD: upper and lower body dyskinesia, speech, and tremor. Speech and phonation were measured through measurements of vocal volume, articulation, raspiness or hoarseness, volume decay, and expressiveness. Upper body and lower body bradykinesia were measured through slowness, restricted movement, and arrhythmia, with additional testing for stability in the lower body achieved through measurements of balance and U-turn (speed of turning while walking). The tremor was assessed through measurements of postural tremor and rest tremor. To decide upon these tests, Roche mapped 767 features to neurobiological concepts. These features were evaluated based on their test-retest reliability, validity as demonstrated by known-group differences, sensitivity to six-month progression in stable symptomatic-treated PD patients, and linear progression present in both early PD and the later stages of PD. The feature in each neurobiological category that optimally balanced the aforementioned criteria was selected. In the PASADENA trial, the bradykinesia simple sum score (BSS) was able to show disease progression in patients undergoing symptomatic treatment over six months, with a test-retest reliability of 0.87, as measured by intraclass correlation coefficient (ICC). This indicates that BSS is sensitive to measuring the worsening of motor symptoms in patients with early PD on MAO-B and DA treatments. Motor fluctuations are difficult to measure as they vary throughout the day, so the infrequent collection of clinical data makes the process of monitoring the effects of a potential treatment even more difficult. However, digital tools enable the remote and frequent assessment of motor fluctuations.
The data presented by Roche at AD/PD instils confidence in the DHT feature space and points toward a potential roadmap for honing optimally reliable and valid measures of disease progression in early PD. That being said, the results were driven by a small cohort, and a large-scale study is needed to validate the use of DHTs. The use of DHTs could facilitate the development of more effective clinical endpoints for use in PD clinical trials, which would be beneficial for investigating the efficacy of pipeline assets that may slow or halt disease progression. According to KOLs previously interviewed by GlobalData, there is an unmet need for validated clinical endpoints and biomarkers to evaluate disease progression. The DHTs being pioneered by Roche would be well-placed to address this unmet need, as they offer objective data to measure symptom fluctuations. More precise measurements of everyday motor fluctuations would be able to fill in the blanks caused by the infrequent collection of clinical data.
The integration of DHTs into PD presents a transformative step forward in addressing longstanding challenges in measuring disease progression. By enabling frequent, remote, and objective assessments of motor fluctuations and variability, DHTs provide more robust and sensitive outcome data to supplement traditional clinical scales. As PD remains a complex and unpredictable neurodegenerative disorder, digital innovations offer promising opportunities to refine therapeutic strategies, improve patient care, and address the unmet need for reliable biomarkers. These advancements will pave the way for more precise interventions and a deeper understanding of PD progression, ultimately benefiting patients and researchers alike
