Spastic ataxia Charlevoix-Saguenay type

A complex hereditary NEURODEGENERATIVE DISORDER that exhibits autosomal recessive inheritance. Onset is typically in early childhood and is characterized b CEREBELLAR ATAXIA; PYRAMIDAL TRACT signs, and PERIPHERAL NEUROPATHY. Most patients become wheelchair-bound, but cognitive function is usually not affected. Some patients may have atypical features, such as later onset or initial presentation of peripheral neuropathy. Mutations in the SACS gene have been identified. OMIM: 270550

Also Known As:

Networked: 84 relevant articles (2 outcomes, 7 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Spastic ataxia Charlevoix-Saguenay type
2.	Friedreich Ataxia (Friedreich's Ataxia)
3.	Olivopontocerebellar Atrophies (Olivopontocerebellar Atrophy)
4.	Neurodegenerative Diseases (Neurodegenerative Disease)
5.	Ataxia (Dyssynergia)

Experts

1.	Giunti, Paola: 7 articles (10/2021 - 01/2013)
2.	Brais, Bernard: 7 articles (10/2021 - 06/2011)
3.	Chapple, J Paul: 6 articles (01/2018 - 05/2009)
4.	Santorelli, Filippo Maria: 5 articles (07/2022 - 09/2011)
5.	Santorelli, Filippo M: 5 articles (12/2021 - 01/2011)
6.	Nethisinghe, Suran: 5 articles (10/2021 - 01/2013)
7.	Doccini, Stefano: 4 articles (07/2022 - 01/2020)
8.	Bremner, Fion: 4 articles (01/2021 - 01/2013)
9.	Gehring, Kalle: 4 articles (10/2015 - 06/2011)
10.	Gagnon, Cynthia: 3 articles (09/2022 - 10/2018)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Spastic ataxia Charlevoix-Saguenay type:

1.	AntioxidantsIBA 06/02/2020 - "Their protective antioxidant activity in human healthy primary skin fibroblasts and their therapeutic efficacy in ARSACS-derived primary skin fibroblasts have been also investigated, showing their potential for future development as therapeutic agents." 12/01/2015 - "Therefore, on the basis of our findings, which suggest a potential therapeutic role for antioxidant agents, ARSACS seems to fall within a larger group of disorders. " 07/12/2022 - "In vitro study of polydopamine nanoparticles as protective antioxidant agents in fibroblasts derived from ARSACS patients." 01/01/2023 - "A mitochondrial-targeted antioxidant (MitoQ) improves motor coordination and reduces Purkinje cell death in a mouse model of ARSACS." 07/12/2022 - "In this work, we assessed the effect of PDNPs on human fibroblasts derived from ARSACS patients in terms of antioxidant properties and protein expression. "
2.	mitoquinoneIBA 01/01/2023 - "Our data suggest that MitoQ is a potential therapeutic treatment for ARSACS and that it improves motor coordination via increasing cerebellar Purkinje cell mitochondria function and reducing Purkinje cell death." 01/01/2023 - "Purkinje cells in anterior vermis of Sacs-/- mice normally undergo cell death in ARSACS; however, Purkinje cells numbers were elevated after chronic MitoQ treatment. " 01/01/2023 - "A mitochondrial-targeted antioxidant (MitoQ) improves motor coordination and reduces Purkinje cell death in a mouse model of ARSACS." 01/01/2023 - "We investigated whether mitochondrial function could be restored in Sacs-/- mice, a mouse model of ARSACS, using the mitochondrial-targeted antioxidant ubiquinone MitoQ. "
3.	Proteins (Proteins, Gene)FDA Link 01/10/2023 - "This article has provided a review for the structure and function of sacsin protein and the mechanisms underlying abnormalities of sacsin in ARSACS disease." 01/01/2023 - "To investigate the impact of the mutated sacsin protein in these cells in vitro, induced pluripotent stem cell- (iPSC-) derived motor neurons and iPSC-derived Purkinje cells were generated from three ARSACS patients. " 12/01/2022 - "Correction: The ARSACS disease protein sacsin controls lysosomal positioning and reformation by regulating microtubule dynamics." 11/01/2022 - "Our findings suggest that disrupted trafficking of synaptic adhesion proteins is a causal molecular deficit in ARSACS." 01/01/2022 - "The ARSACS disease protein sacsin controls lysosomal positioning and reformation by regulating microtubule dynamics."
4.	VimentinIBA 10/29/2021 - "This study shows that ARSACS patient cells have significantly increased vimentin bundling compared to control, and this was also present in ARSACS carriers despite them being asymptomatic. " 01/01/2017 - "To investigate if loss of sacsin affects intermediate filaments more generally, the distribution of vimentin was analysed in ARSACS patient fibroblasts and in cells where sacsin expression was reduced. " 10/29/2021 - "Our preliminary findings presented here suggest that targeting the heat-shock response by Hsp90 inhibition alleviates vimentin bundling and may represent a promising area for the development of therapeutics for ARSACS." 01/01/2017 - "In ARSACS patient fibroblasts HSP70, ubiquitin and the autophagy-lysosome pathway proteins Lamp2 and p62 relocalized to the area of the vimentin accumulation. "
5.	EndocannabinoidsIBA 09/01/2022 - "While our study did not assess the therapeutic effects of cannabis, our results highlight that there is a potential role for cannabis and cannabinoids in the management of multiple ARSACS-associated symptoms and that agents modulating the endocannabinoid system need to be properly investigated."
6.	Therapeutic UsesIBA 09/01/2022 - "While our study did not assess the therapeutic effects of cannabis, our results highlight that there is a potential role for cannabis and cannabinoids in the management of multiple ARSACS-associated symptoms and that agents modulating the endocannabinoid system need to be properly investigated."
7.	Molecular Chaperones (Chaperone, Molecular)IBA 08/26/2011 - "In this study, we assign a novel molecular chaperone activity to the protein sacsin responsible for autosomal recessive spastic ataxia of Charlevoix-Saguenay, a degenerative disorder of the cerebellum and spinal cord. "
8.	Tryptophan (L-Tryptophan)FDA Link 05/01/2001 - "The aims of the present study were: i) to measure levels of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxindoleacetic acid (5HIAA) and precursor tryptophan, as well as the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and thiamine in the cerebrospinal fluid (CSF) of patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA), and the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSAC), as compared with sex- and age-matched control subjects. "
9.	Thiamine (Aneurin)FDA Link 05/01/2001 - "The aims of the present study were: i) to measure levels of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxindoleacetic acid (5HIAA) and precursor tryptophan, as well as the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and thiamine in the cerebrospinal fluid (CSF) of patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA), and the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSAC), as compared with sex- and age-matched control subjects. "
10.	Serotonin (5 Hydroxytryptamine)IBA 05/01/2001 - "The aims of the present study were: i) to measure levels of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxindoleacetic acid (5HIAA) and precursor tryptophan, as well as the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and thiamine in the cerebrospinal fluid (CSF) of patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA), and the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSAC), as compared with sex- and age-matched control subjects. "

Therapies and Procedures

1.	Activities of Daily Living (ADL) 04/27/2023 - "This study aimed to document the natural history of ARSACS over a 4-year period in terms of upper and lower limb functions, balance, walking capacity, performance in daily living activities, and disease severity. " 10/02/2018 - "To document the decline of upper and lower limb functions, mobility, and independence in daily living activities in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) over a 2-year period. "
2.	Walkers 10/14/2021 - "This study aimed to describe lower limbs impairments, balance and activity limitations related to indoor mobility in adult walkers with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). "
3.	Therapeutics 12/01/2022 - "Lastly in the perspectives section, we address gene correction strategies for monogenic disorders such as ARSACS, along with their common delivery methods, representing a hopeful area for ARSACS therapeutics development." 06/02/2020 - "In order to design a suitable therapy for ARSACS, it is essential to consider that treatments need to cross the blood-brain barrier (BBB), a specialized structure that separates the subtle environment of the brain from blood circulation. " 08/05/2021 - "Although mouse models of ARSACS mimic largely the disease progression seen in humans, their use in the validation of effective therapies has not yet been proposed. " 10/29/2021 - "Our preliminary findings presented here suggest that targeting the heat-shock response by Hsp90 inhibition alleviates vimentin bundling and may represent a promising area for the development of therapeutics for ARSACS."
4.	Conservative Treatment 12/01/1999 - "As a complement to conservative treatment, surgery has a place in the care of patients with ARSACS. "