Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38
Open Access
- 4 October 2017
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 82 (4), 615-621
- https://doi.org/10.1002/ana.25059
Abstract
Objective Spinocerebellar ataxia 38 (SCA38) is caused by mutations in the ELOVL5 gene, which encodes an elongase involved in the synthesis of polyunsaturated fatty acids, including docosahexaenoic acid (DHA). As a consequence, DHA is significantly reduced in the serum of SCA38 subjects. In the present study, we evaluated the safety of DHA supplementation, its efficacy for clinical symptoms, and changes of brain functional imaging in SCA38 patients. Methods We enrolled 10 SCA38 patients, and carried out a double‐blind randomized placebo‐controlled study for 16 weeks, followed by an open‐label study with overall 40‐week DHA treatment. At baseline and at follow‐up visit, patients underwent standardized clinical assessment, brain 18‐fluorodeoxyglucose positron emission tomography, electroneurography, and ELOVL5 expression analysis. Results After 16 weeks, we showed a significant pre–post clinical improvement in the DHA group versus placebo, using the Scale for the Assessment and Rating of Ataxia (SARA; mean difference [MD] = +2.70, 95% confidence interval [CI] = +0.13 to + 5.27, p = 0.042). At 40‐week treatment, clinical improvement was found significant by both SARA (MD = +2.2, 95% CI = +0.93 to + 3.46, p = 0.008) and International Cooperative Ataxia Rating Scale (MD = +3.8, 95% CI = +1.39 to + 6.41, p = 0.02) scores; clinical data were corroborated by significant improvement of cerebellar hypometabolism (statistical parametric mapping analyses, false discovery rate corrected). We also showed a decreased expression of ELOVL5 in patients’ blood at 40 weeks as compared to baseline. No side effect was recorded. Interpretation DHA supplementation is a safe and effective treatment for SCA38, showing an improvement of clinical symptoms and cerebellar hypometabolism. Ann Neurol 2017;82:615–621Funding Information
- Fondazione Telethon (GGP14225)
This publication has 25 references indexed in Scilit:
- Movement disorders in spinocerebellar ataxiasMovement Disorders, 2011
- Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyondThe Lancet Neurology, 2010
- Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's diseaseJournal of Lipid Research, 2009
- Deletion of ELOVL5 leads to fatty liver through activation of SREBP-1c in miceJournal of Lipid Research, 2009
- Coenzyme Q10 and vitamin E deficiency in Friedreich’s ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapyEuropean Journal of Neurology, 2008
- Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liverProstaglandins, Leukotrienes & Essential Fatty Acids, 2007
- Friedreich’s ataxia: Coenzyme Q10 and vitamin E therapyMitochondrion, 2007
- Low liver conversion rate of α-linolenic to docosahexaenoic acid in awake rats on a high-docosahexaenoate-containing dietJournal of Lipid Research, 2006
- α‐Linolenic acid does not contribute appreciably to docosahexaenoic acid within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic acidJournal of Neurochemistry, 2005
- Brain phospholipids and fatty acids in Friedreich's ataxia and spinocerebellar atrophy type‐1Movement Disorders, 1998