Friedreich's ataxia: a descriptive epidemiological study in an Italian population

Leone, Maurizio; Brignolio, F; Rosso, Michela; Curtoni, E. S.; Moroni, Antonio; Tribolo, Antonella; Schiffer, Davide

doi:10.1111/j.1399-0004.1990.tb03566.x

Cited by 42 publications

(17 citation statements)

References 18 publications

(28 reference statements)

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“…20), but a clear case has been made for their therapeutic efficacy in neurodegenerative disorders. Previously it was unknown whether estrogens and estrogen-like compounds had any effect on the pathogenesis of Friedreich's ataxia, although the observation that females tend to have less severe symptoms and a later onset of the disease process (2) suggests that there is a beneficial effect of estrogens in this disease process. For the first time, this study presents data showing that estrogens and estrogen-like compounds containing a phenol ring are protective against oxidative stress in FRDA cells and that this process is not mediated by any known ER.…”

Section: Discussionmentioning

confidence: 97%

“…Estrogen has been demonstrated to have antioxidant properties (31)(32)(33)(34)(35); modulate Ca 2ϩ flux (36); stabilize mitochondrial membrane potential (20,34,35); maintain the activity of electron transport chain complexes I, III, and IV; help to maintain aerobic ATP production (34,37); and promote a favorable balance of antiapoptotic-proapoptotic proteins in the cell (20,30). Although the neuroprotective effects of estrogens have never been tested in an FRDA model and FRDA shows no gender bias in incidence (21,22), epidemiological studies of FRDA have shown a better prognosis in female patients (2), and the proposed mitochondrial-support mechanisms of E2 suggests a possible role for E2 in the prevention and treatment of FRDA symptoms (38).…”

mentioning

confidence: 96%

“…F riedreich's ataxia (FRDA) is the most common form of inherited ataxia in the world, affecting 1:20,000 to 1:50,000 people in the United States (1)(2)(3)(4)(5). It is inherited in an autosomal recessive manner due to a GAA trinucleotide repeat expansion in the first intron of the FXN gene on chromosome 9q13-21, causing gene silencing and a functional absence of the mitochondrial-localizing protein frataxin (1,(5)(6)(7)(8)(9).…”

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confidence: 98%

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Estrogen Protection in Friedreich's Ataxia Skin Fibroblasts

2011

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Estrogens have been shown to have protective effects on a wide range of cell types and animal models for many neurodegenerative diseases. The present study demonstrates the cytoprotective effects of 17β-estradiol (E2) and estrogen-like compounds in an in vitro model of Friedreich's ataxia (FRDA) using human donor FRDA skin fibroblasts. FRDA fibroblasts are extremely sensitive to free radical damage and oxidative stress, produced here using l-buthionine (S,R)-sulfoximine to inhibit de novo glutathione synthesis. We have shown that the protective effect of E2 in the face of l-buthionine (S,R)-sulfoximine -induced oxidative stress is independent of estrogen receptor-α, estrogen receptor-β or G protein-coupled receptor 30 as shown by the inability of either ICI 182,780 or G15 to inhibit the E2-mediated protection. These cytoprotective effects appear to be dependent on antioxidant properties and the phenolic structure of estradiol as demonstrated by the observation that all phenolic compounds tested were protective, whereas all nonphenolic compounds were inactive, and the observation that the phenolic compounds reduced the levels of reactive oxygen species, whereas the nonphenolic compounds did not. These data show for the first time that phenolic E2-like compounds are potent protectors against oxidative stress-induced cell death in FRDA fibroblasts and are possible candidate drugs for the treatment and prevention of FRDA symptoms.

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Section: Discussionmentioning

confidence: 97%

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confidence: 96%

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confidence: 98%

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Estrogen Protection in Friedreich's Ataxia Skin Fibroblasts

2011

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“…Furthermore, few studies separate the prevalence of ataxia in children vs adults. [4][5][6][7][8][9][10][11][12] Given the multitude of ataxia-causing conditions and recognizing that each can be quite rare, the overall prevalence of childhood ataxia is likely underestimated. Yet overall prevalence data are needed to accurately assess the impact and societal cost of childhood ataxia.…”

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confidence: 99%

Prevalence of ataxia in children

et al. 2014

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Objective: To estimate the prevalence of childhood ataxia resulting from both genetic and acquired causes.Methods: A systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement. Five databases were searched for articles reporting a frequency measure (e.g., prevalence, incidence) of ataxia in children. Included articles were first grouped according to the World Health Organization (WHO) regions and subsequently classified according to etiology (genetic, acquired, or mixed). Each article was assessed for its risk of bias on the domains of sampling, measurement, and analysis. Incidence values were converted to prevalence estimates whenever possible. European prevalence estimates for different etiologies of ataxia were summed to gauge the overall prevalence of childhood ataxia.Results: One hundred fifteen articles were included in the review. More than 50% of the data originated from the Europe WHO region. Data from this region also showed the least susceptibility to bias. Little data were available for Africa and Southeast Asia. The prevalence of acquired ataxias was found to vary more greatly across regions than the genetic ataxias. Ataxic cerebral palsy was found to be a significant contributor to the overall prevalence of childhood ataxia across WHO regions. The prevalence of childhood ataxias in Europe was estimated to be ;26/100,000 children and likely reflects a minimum prevalence worldwide. Conclusions:The findings show that ataxia is a common childhood motor disorder with a higher prevalence than previously assumed. More research concerning the epidemiology, assessment, and treatment of childhood ataxia is warranted. Ataxia refers to a lack or loss of movement coordination. It is associated with damage or dysfunction of the cerebellum or its afferent and efferent projections.1 Ataxia is especially debilitating for children because they are still developing and learning motor competency. The prevalence of some ataxia-causing conditions has been reported. However, most reports are focused on a single condition and a specific geographical location, making it difficult to generalize the prevalence estimates. Furthermore, few studies separate the prevalence of ataxia in children vs adults. [4][5][6][7][8][9][10][11][12] Given the multitude of ataxia-causing conditions and recognizing that each can be quite rare, the overall prevalence of childhood ataxia is likely underestimated. Yet overall prevalence data are needed to accurately assess the impact and societal cost of childhood ataxia.The purpose of this article is to systematically review the literature on the prevalence of ataxia in children across World Health Organization (WHO) regions. The prevalence of childhood From the Department of Neuroscience

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“…First diagnosed by Nikolaus Friedreich in 1863 (Friedreich, 1863a, 1863b, 1863c, 1876, 1877), Friedreich’s ataxia (FA) affects 1 in 50,000 people worldwide with a carrier rate of 1 in 120 making it the most common type of inherited ataxia worldwide (Bradley et al, 2000; Campuzano et al, 1996; Harding, 1983; Leone et al, 1990; Pandolfo, 1998; Schulz et al, 2009). This disorder is autosomal recessive and found mainly in descendents of Mediterranean cultures in Europe, the Middle Eastern and North Africa (Labuda et al, 2000).…”

Section: Introduction Symptoms and Disease Progressionmentioning

confidence: 99%

Therapeutic strategies in Friedreich's Ataxia

Richardson

Kelly

et al. 2013

Brain Research

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First established as a diagnosis by Nikolaus Friedreich in 1863, Friedreich’s ataxia (FA) is an autosomal recessive progressive neurodegenerative disorder cause by a trinucleotide repeat expansion. FA begins with the functional absence of the FXN gene product frataxin, a protein whose exact function still remains unknown. This absence results in impaired intracellular antioxidant defenses, dysregulation of iron-sulfur cluster proteins, depression of aerobic electron transport chain respiration, massive mitochondrial dysfunction, and ultimately cell death in the brain, spinal cord and heart. Herein, we review the molecular and cellular pathogenesis leading to widespread organ system dysfunction, as well as current therapeutic research aimed at preventing the debilitating effects of frataxin loss and preventing the signs and symptoms associated of FA. We also discuss the ongoing treatment strategies employed by our laboratory to prevent mitochondrial damage using synergistic effects of 17β-estradiol and methylene blue, previously shown by our group and others to have protective effects in human FA fibroblasts. This article is part of a Special Issue entitled Hormone Therapy.

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Friedreich's ataxia: a descriptive epidemiological study in an Italian population

Cited by 42 publications

References 18 publications

Estrogen Protection in Friedreich's Ataxia Skin Fibroblasts

Estrogen Protection in Friedreich's Ataxia Skin Fibroblasts

Prevalence of ataxia in children

Therapeutic strategies in Friedreich's Ataxia

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