Pathogenic Insights and Search for Biomarkers in RFC1-ataxia/CANVAS

Condition(s) studied

Investigational drug(s) / intervention(s)

Assessment of markers of oxidative stress in peripheral blood samples: Participants will perform serial blood samples at interval of 12 months to compare levels of markers of oxidative stress

Study summary

CANVAS (Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome), also referred to as RFC1-ataxia, is a recently molecularly characterized neurodegenerative disorder caused by a biallelic expansion of an AAGGG pentanucleotide repeat in intron 2 of the Replication Factor C subunit 1 (RFC1) gene.

This adult-onset condition presents with a variable combination of cerebellar ataxia, peripheral neuropathy, and vestibular dysfunction. Currently, limited data are available regarding its natural history and the molecular mechanisms by which this dynamic mutation leads to neurodegeneration of selective neuronal populations.

Given that recent literature identifies RFC1/CANVAS as a relatively common genetic cause of late-onset ataxia, elucidation of its underlying pathogenic mechanisms may offer insights into the molecular pathways implicated in more prevalent late-onset neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease.

Eligibility

Primary outcome measure(s)

• Scale for the Assessment and Rating of Ataxia (SARA) scale — 1 year
  SARA is a clinical scale validated in degenerative ataxias, which assesses a range of different impairments related to cerebellar dysfunction. The scale is made up of 8 items related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test ; Each item scores from 0 ( no impairment) to 4 ( maximum impairment) Global SARA score ranges from 0 (no cerebellar ataxia ) to 40 (maximal severity of ataxia )
• INTERNATIONAL CO-OPERATIVE ATAXIA RATING SCALE (ICARS) — 1 year
  ICARS is another, recommended outcome scale for cerebellar ataxias, including 19 items and 4 subscales evaluating postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders (14); Each subscale has an ordinal scale with 0 indicating normal and the higher score indicating greatest impairment or that the patient is unable to complete the task. Global score ranges from 0 to 100 : higher score indicates greater impairment
• SENSORY ATAXIA RATING SCALE (SEARS) — 1 year
  SEARS is a 10-item functional scale developed and validated to cover the clinical spectrum of manifestations in patients with sensory neuronopathies. It has been validated for any forms of sensory ataxia, including 10-meter walking test (10mWT) to assess gait speed. Scores range from 0 (no impairment) to 41 (maximal impairment)
• Berg Balance Scale (BBS) — 1 year
  BBS for balance assessment is an ordinal scale ranging from 0 to 56, consisting of 13 items with a score from 0 to 4 where 0 is the minimum performance and 4 is the maximum performance regarding the item required. This scale mainly evaluates the static balance and minimally the dynamic
• Tinetti scale — 1 year
  The Tinetti Assessment Tool is a simple test that measures both gait and balance abilities based on performing specific tasks. Scoring of the Tinetti Assessment Tool is done on a 3-point ordinal scale with a range of 0 to 2, where 0 represents the most impairment, while 2 represents independence. The individual scores are then combined to form three measures: an overall gait assessment score (maximum score 12), overall balance assessment score (maximum score 16), combined gait and balance score (maximum total score is 28). Scores below 19 indicate high risk for falls
• Dizziness Handicap Inventory Scale (DHI) — 1 year
  The DHI evaluates the self-perception of the incapacitating effects, on the quality of life, caused by dizziness. It comprises 25 items with a total score ranging between 0 and 100 points. DHI can be further subdivided into physical (DHI-P, 28 points), functional (DHI-F 36 points) and emotional (DHI-E 36 points) sub scores. A higher score indicates a more severe handicap.

Trial sites (2)

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