Positive effect of immunomodulatory therapies on disease progression in Huntington's disease? Data from a real-world cohort.

Background

The role of neuroinflammation and autoimmune processes in neurodegenerative diseases is not fully understood. Activation of microglia with expression of proinflammatory cytokines supports the hypothesis that immune processes may play an important role in the pathophysiology of Huntington's disease (HD) and thus, immunomodulating therapies might have potential neuroprotective properties. Until now, no disease-modifying therapy (DMT) is available for HD.

Objective

The aim of this research was to characterize a cohort of patients suffering from both HD and autoimmune demyelinating diseases of the central nervous system (classified as G35-37 in ICD-10; ADD-CNS) in comparison to HD cases without ADD-CNS. In particular, we were interested to investigate potential modulating effects on disease manifestation and progression of HD over time of prescribed immunomodulating medications (DMT).

Methods

We analyzed the course of HD regarding motoric, functional, and cognitive aspects, using longitudinal data of up to 2 years from the worldwide registry study ENROLL-HD. Additional cross-sectional data in the largest cohort worldwide of HD patients was analyzed using demographic and molecular genetic parameters. Data were analyzed using analysis of variance (ANOVA) for cross-sectional and repeated-measures ANOVA for longitudinal parameters in IBM SPSS Statistics V.27.

Results

Within the ENROLL-HD database, we investigated

Conclusion

Patients suffering from motor-manifest HD and simultaneously from ADD-CNS have better cognitive capacities compared with other motor-manifest HD patients. Moreover, DMTs might have beneficial effects on progression of neurodegeneration including the motor phenotype. However, this effect might have been biased by younger age in DMT-treated patients. Pre-manifest HD patients showed more functional impairment as expected due to their additional ADD-CNS disease.

Informations de copyright

© The Author(s), 2022.

Déclaration de conflit d'intérêts

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.A. declares no conflict of interest. C.S. reports personal fees/honoraria from Teva Pharma GmbH, as well as non-financial support and other support from ENROLL-HD study (CHDI), PRIDE-HD (TEVA, Neurosearch), PROOF-HD (Prilenia), LEGATO (TEVA), and Amaryllis (Pfizer), AFQ056 (Novartis), ASO (IONIS Pharmaceuticals, Roche AG, WAVE) for the conducting of studies and grants from Biogen, the German Huntington foundation, and CHDI all outside the submitted work and without relevance to the manuscript. S.F. received speaker’s or scientific advisory board honoraria from Biogen, BMS, Celgene, Novartis, and Roche and grant support from Ruhr-University Bochum, DMSG, Stiftung für therapeutische Forschung, and Novartis, unrelated to the content of this manuscript. G.E. received speaker’s or scientific advisory board honoraria from Biogen, BMS, Celgene, Novartis, and Roche and grant support from Ruhr-University Bochum, none related to this manuscript.