Recent Advances in the Treatment of Cerebellar Disorders

Abstract

Various etiopathologies affect the cerebellum, resulting in the development of cerebellar ataxias (CAs), a heterogeneous group of disorders characterized clinically by movement incoordination, affective dysregulation, and cognitive dysmetria. Recent progress in clinical and basic research has opened the door of the ‘‘era of therapy” of CAs. The therapeutic rationale of cerebellar diseases takes into account the capacity of the cerebellum to compensate for pathology and restoration, which is collectively termed cerebellar reserve. In general, treatments of CAs are classified into two categories: cause-cure treatments, aimed at arresting disease progression, and neuromodulation therapies, aimed at potentiating cerebellar reserve. Both forms of therapies should be introduced as soon as possible, at a time where cerebellar reserve is still preserved. Clinical studies have established evidence-based cause-cure treatments for metabolic and immune-mediated CAs. Elaborate protocols of rehabilitation and non-invasive cerebellar stimulation facilitate cerebellar reserve, leading to recovery in the case of controllable pathologies (metabolic and immune-mediated CAs) and delay of disease progression in the case of uncontrollable pathologies (degenerative CAs). Furthermore, recent advances in molecular biology have encouraged the development of new forms of therapies: the molecular targeting therapy, which manipulates impaired RNA or proteins, and the neurotransplantation therapy, which delays cell degeneration and facilitates compensatory functions. The present review focuses on the therapeutic rationales of these recently developed therapeutic modalities, highlighting the underlying pathogenesis.

The inherited cerebellar ataxias: an update

“…Allele-specific approaches are advisable since consequences due to wild type protein decrease could be harmful. Other therapies targeting RNA inhibiting gene expression are RNA interference (RNAi), micro RNA (miRNA), short hairpin RNA (shRNA) [ 60 ], gene editing strategies (CRISPR/Cas9) [ 61 ]. For now, in ATX-FXN, the only treatment that has shown positive results is omaveloxolone.…”

Effects of Anodal Cerebellar Transcranial Direct Current Stimulation on Movements in Patients with Cerebellar Ataxias: A Systematic Review

“…A total of 397 records were identified from the databases and reduced to 57 records after removal of duplicates (Figure 1). Among the 57 records, 52 records were further excluded: 40 records were reviews [6,16,18,19,22,[25][26][27][28][29][30][31][32][33][34], conference proceedings [35][36][37][38][39][40], responses [41,42], editors' notes [43], letters to the editors [44], reports [45], corrections [46], updates [47], theoretical papers [48], commentaries [49,50], book chapters [51], published protocols [52], or clinical trials registration records [53][54][55][56][57][58][59]; two studies did not recruit human participants [60,61]; one study did not recruit patients with cerebellar ataxias [62]; one study did not apply tDCS [63]; three studies used cranial electrotherapy stimulation, CES…”

Expression of 1L-myo-Inositol -1-Phosphate Synthase (EC 5.5.1.4) is Deregulated in the Cerebellum of Curly Tail Mutant Mice

“…Studies of the cerebellum have extended its function of motor control to non-motor activities as well, including language, thought modulations, emotions and the ability to organize symbolic activities consecutively [23,24,25]. Moreover, inositol metabolism has been connected to both motor and non-motor functions of the cerebellum.…”