efficacy of oral trehalose in spinocerebellar ataxia 3

Conditions: Spinocerebellar Ataxia Type 3

Summary: this study evaluates the effectiveness of oral trehalose in alleviating the neuropathological and motor behaviour deficits among patients with sca3. a total of 40 participants with sca3 will be recruited, with 20 participants to be administered with trehalose while another 20 participants to be administered with a maltose placebo.

spinocerebellar ataxia 3 (sca3) is a rare form of inherited neurodegenerative disease involving progressive degeneration of spinocerebellar tract. sca3 is characterised by increasingly worsening cerebellar function leading to gait abnormalities and poor coordination, dysarthria, and abnormal eye movements. non-ataxia features include pyramidal and extrapyramidal manifestations, sensorimotor, neuropsychological and psychiatric symptoms. this is attributed to the role of cerebellum in motor, cognitive and affective processing (i.e. cerebellar cognitive and affective syndrome; ccas), as well as its extensive connection with cerebral structures. trehalose is an omnipotent disaccharide molecule found in lower and higher life forms except in vertebrates. it has an amorphous (i.e. non-reducing) property, which is shown in its high hydrophilicity, chemical stability and strong resistance to denaturation / breakdown by heat, acid or enzyme. it is also shown to help refold partially denatured protein, thereby stabilizes protein aggregates, including those of polyglutamine, in vivo as well as in vitro. this has provided an avenue in which trehalose as a therapeutic agent for neurodegenerative disorders with pathological changes of protein aggregates. in this study, a double-blinded randomised controlled trial (rct) will be employed. a total of 40 patients with sca3 will be randomly allocated to oral trehalose group and a placebo group (20 participants for each arm). with regards to clinical outcomes, motor and cognitive performances will be assessed to infer the efficacy of trehalose. likewise, structural, resting-state fmri (i.e. functional connectivity), and mr spectroscopy (i.e. metabolism), will be used as imaging biomarkers in this study.

Eligibility criteria:
inclusion criteria: * age between 18 and 85 years old. * genetically confirmed sca 3 diagnosis. * presence of progressive cerebellar syndrome (i.e. symptomatic) and genetic confirmation of sca 3 in one of the immediate family members with similar clinical syndrome. * able to read, speak, and understand english or malay. exclusion criteria: * diagnosis of diabetes mellitus type 1 or type 2 * presence of any concomitant neurological condition that might interfere with clinical measures used in this study. * presence of contraindication or hypersensitivity to trehalose. * use of stimulant / medication, caffeine, and tobacco within less than 24 hours washout period prior to assessment and / or scan. * presence of severe visual and / or auditory perceptual deficits. * mri contra-indications: claustrophobia, pregnancy, electronic implants (e.g. pacemaker) in the body, aneurysm clip, and current or past employment as machinists, welders or metal workers.

Keywords: spinocerebellar ataxia type 3 cerebellar cognitive and affective syndrome trehalose neuropsychology magnetic resonance imaging