Neuroimaging Spectrum at Pre-, Early, and Late Symptomatic Stages of SCA17 Mice

Chen, Chiao Chi; Yao, Nai Wei; Lin, Chia Wei; Su, Wei Shuo; Wu, Chin Tien; Chang, Chen; Hsieh-Li, Hsiu Mei

doi:10.1007/s12311-020-01127-5

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…It is well known that some non-neurological and neurological symptoms (e.g., anosmia in Parkinson’s disease) can be present at the prodromal stage [ 20 , 21 ]. Consistently, a pre-symptomatic or prodromal stage was observed in an animal model of degenerative ataxia [ 22 ]. In patients with degenerative ataxia, pre-ataxic symptoms have recently been reported in gait stability [ 23 ] and ocular movements [ 24 ].…”

Section: Latent Autoimmune Cerebellar Ataxia (Mario Mano Marios Hadji...mentioning

confidence: 56%

Consensus Paper: Latent Autoimmune Cerebellar Ataxia (LACA)

et al. 2023

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Immune-mediated cerebellar ataxias (IMCAs) have diverse etiologies. Patients with IMCAs develop cerebellar symptoms, characterized mainly by gait ataxia, showing an acute or subacute clinical course. We present a novel concept of latent autoimmune cerebellar ataxia (LACA), analogous to latent autoimmune diabetes in adults (LADA). LADA is a slowly progressive form of autoimmune diabetes where patients are often initially diagnosed with type 2 diabetes. The sole biomarker (serum anti-GAD antibody) is not always present or can fluctuate. However, the disease progresses to pancreatic beta-cell failure and insulin dependency within about 5 years. Due to the unclear autoimmune profile, clinicians often struggle to reach an early diagnosis during the period when insulin production is not severely compromised. LACA is also characterized by a slowly progressive course, lack of obvious autoimmune background, and difficulties in reaching a diagnosis in the absence of clear markers for IMCAs. The authors discuss two aspects of LACA: (1) the not manifestly evident autoimmunity and (2) the prodromal stage of IMCA’s characterized by a period of partial neuronal dysfunction where non-specific symptoms may occur. In order to achieve an early intervention and prevent cell death in the cerebellum, identification of the time-window before irreversible neuronal loss is critical. LACA occurs during this time-window when possible preservation of neural plasticity exists. Efforts should be devoted to the early identification of biological, neurophysiological, neuropsychological, morphological (brain morphometry), and multimodal biomarkers allowing early diagnosis and therapeutic intervention and to avoid irreversible neuronal loss.

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Section: Latent Autoimmune Cerebellar Ataxia (Mario Mano Marios Hadji...mentioning

confidence: 56%

Consensus Paper: Latent Autoimmune Cerebellar Ataxia (LACA)

et al. 2023

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“…The predominant pathology observed in SCA17 patients, post-mortem, is significant cerebellar atrophy, which is attributed to the severe loss of Purkinje cells [144,146]. A 2020 study generated a SCA17 transgenic mouse model harbouring 109 CAG repeats in the human TBP transcript under the Purkinje cell-specific L7/pcp2 promoter [147]. The group aimed to investigate the neuroimaging spectrum at various symptomatic stages (pre-, early, and late stages) using magnetic resonance imaging.…”

Section: Spinocerebellar Ataxia Type 17 (Sca17)mentioning

confidence: 99%

Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies

McIntosh

Wilton

et al. 2021

Biomedicines

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Polyglutamine (polyQ) ataxias are a heterogenous group of neurological disorders all caused by an expanded CAG trinucleotide repeat located in the coding region of each unique causative gene. To date, polyQ ataxias encompass six disorders: spinocerebellar ataxia types 1, 2, 3, 6, 7, and 17 and account for a larger group of disorders simply known as polyglutamine disorders, which also includes Huntington’s disease. These diseases are typically characterised by progressive ataxia, speech and swallowing difficulties, lack of coordination and gait, and are unfortunately fatal in nature, with the exception of SCA6. All the polyQ spinocerebellar ataxias have a hallmark feature of neuronal aggregations and share many common pathogenic mechanisms, such as mitochondrial dysfunction, impaired proteasomal function, and autophagy impairment. Currently, therapeutic options are limited, with no available treatments that slow or halt disease progression. Here, we discuss the common molecular and clinical presentations of polyQ spinocerebellar ataxias. We will also discuss the promising antisense oligonucleotide therapeutics being developed as treatments for these devastating diseases. With recent advancements and therapeutic approvals of various antisense therapies, it is envisioned that some of the studies reviewed may progress into clinical trials and beyond.

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