Effects of a balanced replacement treatment by polyunsaturated fatty acids on a murine model of SCA38.

The Spinocerebellar ataxia type 38 (SCA38) is a rare neurodegenerative disease with a pure cerebellar phenotype caused by two missense mutations in ELOVL5 gene, which encodes for an enzyme essential for the elongation of both ω-3 and ω-6 fatty acids, precursors for polyunsaturated fatty acids (PUFAs). Elovl5 knock out mice recapitulate the main symptoms of SCA38 patients, such as motor deficits, hyposmia, peripheral neuropathy and cerebellar atrophy. Since dietary supplementation has been proven to be a simple and low risk method to improve the outcome of different neurodegenerative diseases, the purpose of this work is to assess whether it is possible to rescue the SCA38 phenotype by overcoming the loss of function of ELOVL5 gene by administering its downstream products, ω-3 and ω-6 PUFAs (DHA, EPA, ARA). The balanced replacement treatment by PUFAs was administered to a cohort of mice divided in two groups starting the therapy at two different time points of their life. To assess motor symptoms the two groups were subjected to perform the balance beam test. Histological analysis was later performed in order to analyse structural and molecular features of the cerebellum after the treatment. The obtained results led us to assert that Elovl5 loss can be overcome by an early assumption of a PUFA-rich diet, which relieves SCA38 motor symptoms. Despite this evidence, we did not notice any significant improvement in cerebellar atrophy. Therefore, further investigations are required to understand the mechanism underlying this nutraceutical therapy, which could help design more effective SCA38 clinical trials.