Ataxias are rare diseases with a prevalence of < 5 : 100,000. Clinical hallmarks are progressive loss of balance and coordination accompanied by slurred speech. Consequently, people affected by ataxia suffer substantial restrictions of mobility and communicative skills. The cause may be acquired, sporadic, or genetic. In our research we are focussing on Spinocerebellar ataxias (SCA). SCAs are autosomal dominantly inherited diseases with an onset in adult life. Until now, there have been no treatment options, but for the first time, gene therapies for SCA are on the horizon. For the most common PolyQ-SCA, spinocerebellar ataxia type 3 (SCA3), we have built up the largest Spinocerebellar ataxia type 3 (SCA3) cohort, bringing together more than 250 mutation carriers from 10 European and 3 US sites (ESMI). Participants underwent standardized clinical assessment, biosampling as well as 3T MR imaging. In analyses of large pooled retrospective cohort data with more than 1400 SCA1, SCA2, SCA3, and SCA6 mutation carriers and > 3600 visits, we explore which clinical features predict disease progression. We use ultra-high field magnetic resonance imaging (MRI) at 7T to detect early imaging signs of neurodegeneration that have the potential to serve as stratification or progression biomarkers (SCAIFIELD). Our aim is to establish SCA disease models enriched with information on fluid and imaging biomarkers as well as digital motor behavior read outs, e.g. wearables, marker less tracking, in particular for the pre-ataxic stage before the clinical onset of the disease. This will pave the way towards the intriguing option of genetic treatments trials in pre-ataxic mutation carriers.
- Disease modelling
- Analyses of structural MRI at 3T and 7T MRI (e.g. T1, DWI, QSM) to identify imaging biomarker
- Automated analyses of structural MRI (AI based cerebellar subsegmentation)
5 selected publications
- Faber J, Schaprian T, Berkan K, Reetz K, França MC Jr, de Rezende TJR, Hong J, Liao W, van de Warrenburg B, van Gaalen J, Durr A, Mochel F, Giunti P, Garcia-Moreno H, Schoels L, Hengel H, Synofzik M, Bender B, Oz G, Joers J, de Vries JJ, Kang JS, Timmann-Braun D, Jacobi H, Infante J, Joules R, Romanzetti S, Diedrichsen J, Schmid M, Wolz R, Klockgether T. (2021) Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3. Mov Disord., doi: 10.1002/mds.28610. (Online ahead of print)
- Faber J, Giordano I, Jiang X, Kindler C, Spottke A, Acosta-Cabronero J, Nestor PJ, Machts J, Düzel E, Vielhaber S, Speck O, Dudesek A, Kamm C, Scheef L, Klockgether T. (2020) Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type. Mov Disord. 35(5):816-824.
- Wilke C, Haas E, Reetz K, Faber J, Garcia-Moreno H, Santana MM, van de Warrenburg B, Hengel H, Lima M, Filla A, Durr A, Melegh B, Masciullo M, Infante J, Giunti P, Neumann M, de Vries J, Pereira de Almeida L, Rakowicz M, Jacobi H, Schüle R, Kaeser SA, Kuhle J, Klockgether T, Schöls L; SCA3 neurofilament study group, Barro C, Hübener-Schmid J, Synofzik M. (2020) Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and mice. EMBO Mol Med. doi: 10.15252/emmm.201911803.
- Reber TP*, Faber J*, Niediek J, Bostrom J, Elger CE, Mormann F. (2017) Single-Neuron Correlates of Conscious Perception in the Human Medial Temporal Lobe. Curr Biol., doi: 10.1016/j.cub.2017.08.025; * contributed equally
- Grobe-Einsler M, Taheri Amin A, Faber J, Schaprian T, Jacobi H, Schmitz-Hübsch T, Diallo A, Tezenas du Montcel S, Klockgether T. Development of SARAhome , a New Video-Based Tool for the Assessment of Ataxia at Home. Mov Disord. 2021 May;36(5):1242-1246. doi: 10.1002/mds.28478. Epub 2021 Jan 12. PMID: 33433030.