Objective: To evaluate the safety and efficacy of docosahexaenoic acid supplementation in patients with spinocerebellar ataxia 38 (SCA 38), on clinical symptoms and changes of brain functional imaging.

Background: SCA 38 is caused by mutations in the ELOVL5 gene, which encodes an elongase enzyme involved in the synthesis of very long-chain fatty acids with a high and specific expression in Purkinje cells, causing both an altered function of the enzyme and a possible gain of function. Its main products are docosahexaenoic acid (DHA) and eicosapentaenoic acid. Mutations in the ELOVL5 gene cause both an altered function of the enzyme and a possible gain of function, with a subsequent reduction of serum DHA, and increased ELOVL5 gene expression and protein levels induced by transcriptional feedback regulation.

Methods: Patients underwent a double-blind randomized placebo-controlled study for 16 weeks, followed by an 102-week open-label study with DHA treatment. At baseline (T0) and at follow-up visit (T1=16 weeks; T2=40 weeks; T3=64 weeks; T4=88 weeks; T5=112 weeks), patients underwent standardized clinical assessment, including the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS), brain 18-fluorodeoxyglucose positron emission tomography (FDG-PET), electroneurography, and ELOVL5 expression analysis

Results: 10 patients with SCA 38 were enrolled. At T1 (16 weeks), we observed a significant clinical improvement in the SARA score in the DHA versus placebo group. At T2 (40 weeks), we observed a clinical improvement in both SARA and ICARS scores, associated by a significant improvement of cerebellar hypometabolism evaluated with FDG-PET. We also observed a decreased expression of serum ELOVL5 at T2 compared to baseline. Furthermore, we observed a stabilisation of clinical symptoms at long-term follow-up (T3=64 weeks; T4=88 weeks; T5=102 weeks) [figure1]. No side effect was recorded.

Conclusions: Supplementation with DHA is safe and effective on clinical symptoms and cerebellar hypometabolism, at short and long-term, in patients with SCA38.

References: Manes M, Alberici A, Di Gregorio E, et al. Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38. Ann Neurol 2017;82:615-621. Di Gregorio E, Borroni B, Giorgio E, et al. ELOVL5 mutations cause spinocerebellar ataxia 38. Am J Hum Genet 2014;95:209-217.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/treatment-with-docosahexaenoic-acid-in-spinocerebellar-ataxia-38/