Research presented at the International Ataxia Research Conference in September 2017 and published in a medical journal, highlights a treatment option for a very rare form of ataxia.
What causes SCA38?
A team at the University of Brescia in Italy found the gene causing SCA38 in three Italian families with late-onset, slowly progressive ataxia. Most of these patients also had nystagmus (involuntary eye movement), pes cavus (hollow foot sole) and a reduced sense of smell.
Following on from that discovery in 2014, the team studied the cellular mechanisms that cause the condition. The researchers found that SCA38 is caused by mutations in a gene called ELOVL5, which codes for an enzyme that makes polyunsaturated fatty acids, including one called docosahexaenoic acid (DHA). Usually, this enzyme is found in high levels, mostly in the cerebellum. In SCA38, however, the enzyme’s function is affected and might be harmful, as it reduces the levels of DHA.
This important discovery has led the team to carry out a treatment trial with 10 of their SCA38 patients, testing the effect of supplementing DHA (a dietary fatty acid supplement). The rationale for the trial is two-fold: firstly, to compensate for the reduction in DHA; secondly, because of the low level of DHA in SCA38, levels of the ELOVL5 enzyme are increased. This enzyme is the mutated, harmful version; therefore, increasing DHA levels should decrease the levels of the harmful ELOVL5 mutated protein.
A four-month, double-blind and placebo-controlled trial was performed in 10 people with SCA38 (five on treatment and five on placebo). This was followed by a 40-week period in which every participant took the DHA supplement. Results showed a statistically significant change in
the ataxia symptoms among the treatment group, as measured by the SARA ataxia rating scale (but not the ICARS rating scale), compared to the placebo group. The assessment made with the SARA and ICARS in the 40-week second phase also showed that there was a statistically significant difference between the scores at the start and at the end of the trial. The researchers also measured results by using a brain scanning technique, which reported a change in the cerebellum’s metabolism after the 40-week treatment, compared to baseline. There were no side effects reported.
Although the trial was very small, the lack of side effects and the fact that the treatment is an inexpensive dietary supplement which makes up for the insufficient natural levels, suggests that this could be a treatment option for neurologists to consider for SCA38 patients.
Lead researcher, neurologist Dr Barbara Borroni, told Ataxia UK: “All participants of the trial have chosen to continue taking the DHA supplementation after the trial ended and we are pleased with the continued improvement in their condition. At this stage we are not planning further trials but we would recommend any patients diagnosed with SCA38 to be treated with DHA under the supervision of their neurologist. Due to genetic screening being done in some hospitals in Italy, we are now aware of two further people having been diagnosed with SCA38 and treatment with DHA has been initiated.”
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Ataxia UK magazine, 203, autumn 2018
This important discovery has led the team to carry out a treatment trial with 10 of their SCA38 patients, testing the effect of supplementing DHA (a dietary fatty acid supplement). The rationale for the trial is two-fold: firstly, to compensate for the reduction in DHA; secondly, because of the low level of DHA in SCA38, levels of the ELOVL5 enzyme are increased. This enzyme is the mutated, harmful version; therefore, increasing DHA levels should decrease the levels of the harmful ELOVL5 mutated protein.
Trial shows positive results
A four-month, double-blind and placebo-controlled trial was performed in 10 people with SCA38 (five on treatment and five on placebo). This was followed by a 40-week period in which every participant took the DHA supplement. Results showed a statistically significant change in
the ataxia symptoms among the treatment group, as measured by the SARA ataxia rating scale (but not the ICARS rating scale), compared to the placebo group. The assessment made with the SARA and ICARS in the 40-week second phase also showed that there was a statistically significant difference between the scores at the start and at the end of the trial. The researchers also measured results by using a brain scanning technique, which reported a change in the cerebellum’s metabolism after the 40-week treatment, compared to baseline. There were no side effects reported.
Implications of the results
Although the trial was very small, the lack of side effects and the fact that the treatment is an inexpensive dietary supplement which makes up for the insufficient natural levels, suggests that this could be a treatment option for neurologists to consider for SCA38 patients.
Lead researcher, neurologist Dr Barbara Borroni, told Ataxia UK: “All participants of the trial have chosen to continue taking the DHA supplementation after the trial ended and we are pleased with the continued improvement in their condition. At this stage we are not planning further trials but we would recommend any patients diagnosed with SCA38 to be treated with DHA under the supervision of their neurologist. Due to genetic screening being done in some hospitals in Italy, we are now aware of two further people having been diagnosed with SCA38 and treatment with DHA has been initiated.”
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Ataxia UK magazine, 203, autumn 2018
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