SCA38 Clinical Trial
Official title:
Translating Molecular Pathology Into a Therapeutic Strategy in SCA38, a Newly Identified Form of Spinocerebellar Ataxia
The project will study a therapeutic approach in Spinocerebellar Ataxia (SCA38) by DHA
replacement. SCA38 is caused by missense mutations in the ELOVL5 (Elongation of very long
chain fatty acids protein 5) gene.
Background/Rationale: ELOVL5 is a microsomal fatty acid elongase gene required for the
synthesis of arachidonic acid and DHA. In brain, it shows a peculiar high expression in
cerebellar Purkinje cells.
The ELOVL5 products, such as DHA, are decreased in SCA38 patients serum and DHA administered
as a dietary supplement has been shown to improve SARA scores, to ameliorate quality of life,
and to increase brain cerebellar hypometabolism (FDG-PET) in two SCA38 patients.
Experimental Plan: The investigators will perform a randomized placebo-controlled trial by
DHA supplementation on ten SCA38 patients, followed by an open-label phase.
Expected results: DHA supplementation should be able to improve symptoms in SCA38 and to
improve cerebellar hypometabolism in these patients.
Spinocerebellar ataxias (SCAs) include over thirty different subtypes of central nervous
system diseases that affect approximately 1 in 30,000 persons. The investigators have
identified the causative gene for SCA38, a novel rare form of cerebellar ataxia. Estimated
frequency of the disease is below 1% of SCAs. The disease gene encodes an enzyme involved in
omega-3 fatty acid biosynthesis, whose products are reduced in SCA38 patients' serum.
The investigators reasoned that the administration of specific omega-3 fatty acids could
ameliorate the disease symptoms in SCA38 patients. Indeed, preliminary data obtained in a
pilot trial on two patients, now in their 8th-month therapy, are remarkable, with an
improvement of disease symptoms and quality of life, without any adverse effect.
The investigators will perform a clinical trial to prove this therapeutic strategy of SCA38.
The investigators will evaluate clinical SARA scores, ICARS scores, brain PET images, and
plasma metabolic pattern in ten SCA38 patients.
The trial will consist of two phases: 1) a randomized double-blind placebo/treatment (600 mg
DHA/day) from T0 (baseline observation) to T1 (evaluation at four-month). Patients who will
meet the study eligibility criteria will be randomized to receive the drug or the placebo
(ratio 1:1). A second open-label phase on all patients from T2 (6 months) to T5 (30 months)
will be performed with repeated measures of the medication group (n=10).
Patients will complete a personal diary during the whole treatment and a quality of life
questionnaire at each visit. The primary outcome will be the clinical improvement, whilst
secondary outcome will be considered the improvement of brain metabolism by PET-FDG.
At each time point, clinical evaluation (video-record of SARA/ICARS scores) will be
performed. Videos will be randomized and evaluated blindly by two independently clinicians.
At T0, T1, T2, T5, patients will undergo brain PET-FDG scan. PET-FDG scans will be performed
by the same scanner at the University of Brescia.
This project will provide helpful data on possible replacement treatment in this novel form
of cerebellar degeneration.
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