Skip to content

Bill Nye the Science Guy is speaking at the 2024 Annual Ataxia Conference! Register now.  LEARN MORE!

Fishing for a solution to SCA38 – are omega-3 fatty acids the key to symptom relief?

Written by Dr. Siddharth Nath Edited by Dr. Sriram Jayabal

SCA38 results in a deficiency of an omega-3-fatty acid called docosahexaenoic acid (DHA). Scientists from Italy had shown previously that short-term DHA supplementation reduces disease symptoms. Now, new research from the same group finds that this impact continues with long-term DHA supplementation.

What is SCA38?

One of the rarer forms of ataxia, SCA38 is an autosomal dominant SCA that occurs as a result of mutations in the ELOVL5 gene. This gene contains the recipe for the protein called elongase. It is responsible for building long-chain fatty acids in the brain, including docosahexaenoic acid (DHA), a process key for normal cellular function. Importantly, this protein is found mostly in Purkinje cells, a special type of neuron found within the cerebellum of the brain.

In SCA38, mutant elongase is found primarily in a part of the cell called the Golgi apparatus, which is responsible for packaging proteins and finalizing production, similar to a quality-control technician in an assembly line. Normally, elongase is found at the endoplasmic reticulum, which is further up the assembly line, more akin to the fabrication section.

This mislocation of the protein may explain why it is unable to produce sufficient amounts of long-chain fatty acids to support healthy Purkinje cell function. Deficiencies in DHA resulting from mutations in elongase are detectable by blood tests.

Photo by Pixabay on


You’ve probably heard of omega-3-fatty acids. Omega-3 fatty acids are part of a larger group of molecules called polyunsaturated fatty acids to which the omega-6 fatty acids also belong. DHA is a type of omega-3 fatty acid. Omega-3 fatty acids and omega-6 fatty acids are often touted as a key component of a healthy diet.

Omega-3-fatty acids are important building blocks of the cellular membrane, which is part of all cells in the body. Humans aren’t able to make omega-3-fatty acids ourselves, we need to get them from our diet. That is why many food guides have recommended intakes of omega-3 and omega-6 fatty acids from oily fish and nuts. Vegetarians can also supplement their diet with flaxseed or algae capsules to get these fatty acids in their diet.

DHA is just one of many omega-3-fatty acids and it is most prevalent in the membranes of brain cells, where it plays a key role in normal brain function. Thus, when there is a disturbance or deficiency in the level of DHA, we can expect brain function to become impaired, as is the case in SCA38.

What does this study add?

Since SCA38 is thought to be caused by a deficiency of DHA production by mutant elongase, Dr. Borroni and their team at the University of Brescia in Italy tested whether supplementing DHA in the diet of SCA38 patients would improve/alleviate their symptoms.

In this study, the authors tracked the symptoms of nine SCA38 patients receiving 600 mg of DHA per day by oral supplementation over the course of two years. These results build on earlier studies by the group, which investigated DHA supplementation and tracked symptom relief in the same group for 16-weeks and 40-weeks.

Patients in this study had a confirmed diagnosis of SCA38 and received a daily supplement of 600 mg of DHA. They were then examined five times:

  • The beginning of the study, before any DHA was given to them
  • 40 weeks into the study
  • 62 weeks into the study
  • 82 weeks into the study
  • 104 weeks into the study

At each time point, the patients were assessed using two frequently used SCA symptom scales: the Scale for the Assessment and Rating of Ataxia (SARA), and the International Cooperative Ataxia Rating Scale (ICARS).

In addition to looking at clinical symptoms, patients also underwent brain imaging and blood tests. The brain imaging was to look at how DHA was impacting the brain. The blood tests were used to assess if the treatment regimen actually increased DHA levels in the body.

An important component of the study was the “blinding” of the scientists when it comes to the treatment duration of DHA supplementation. That is, the neurologists rating patient symptoms didn’t know how far along they were in the study. This was accomplished by videotaping each neurological assessment and then having one neurologist review the video to rate the clinical presentation, without any clue as to how long the participant was taking DHA supplement. This type of “blinding” is key to a study such as this one as it prevents researchers from imparting their own bias about the treatment into the assessment of their patients.

Through their examinations, researchers found that DHA supplementation reduced patient symptoms by 62 weeks compared to before the intervention. More importantly, this effect was sustained, meaning that these changes remained while treatment continued for up to 2 years. Blood levels of DHA were slightly increased in all patients receiving treatment, but it was not statistically significant. This means the increase seen could have been due to random chance, rather than the treatment itself. Importantly, there were no side-effects associated with supplementation over the entire two-year course.

So, is DHA the miracle drug for SCA38?

While this study is optimistic, it does not find DHA to be the ‘cure’ but only a possible option to treat SCA38 symptoms. Like all SCAs, SCA38 is progressive, and if left unchecked, will continue to cause damage and death to neurons in the cerebellum. The researchers did not look at whether treatment could restore or fix the damage that has already happened in the brain. But this is something they will need to look at in the future. DHA does show potential promise in reducing the burden of SCA38 symptoms, as it was able to reduce symptoms consistently over two years so long patients continued taking DHA.

However, caution should be taken in drawing strong conclusions from this study. It looked only at a cohort of nine patients, which is a very small number. To gather stronger evidence for DHA, studies with a larger number of participants are required to ensure the result being seen here is not simply a result of chance. Future work in animal models will allow researchers to gain a deeper understanding of what goes awry in the brain of SCA38 patients, and how DHA supplementation helps reduce patient symptoms. This approach of understanding how DHA works as a drug in the human body can help us better understand SCA38 as a disease. If we do that, it could shed light on other treatment strategies for SCA38, possibly even before symptoms begin, allowing it to slow or even prevent the most devastating symptoms caused by the disease.

Key Terms

Elongase: Proteins that help build long-chain fatty acids in the brain, like DHA. One elongase, ELOVL5, is mutated in SCA38 and as a result, doesn’t work very well.

Docosahexaenoic acid (DHA): A type of omega-3-fatty acid that is one of the building blocks used to make cell membranes in the brain.

Polyunsaturated Fatty Acids: Fat molecules, like omega-3 and omega-6 fatty acids. These types of fatty acids are needed to keep your body healthy, but humans can’t make them on their own. They need to get them through the food in their diet. 

Conflict of Interest Statement

The author and editor declare no conflicts of interest.

Citation of Article Reviewed

Manes M, Alberici A, Di Gregorio E, et al. Long-term efficacy of docosahexaenoic acid (DHA) for Spinocerebellar Ataxia 38 (SCA38) treatment: An open label extension study. Parkinsonism Relat Disord. 2019;63:191-194. doi:10.1016/j.parkreldis.2019.02.040

Print Friendly, PDF & Email
Translate »

Join the Ataxia community today!

Become a free member for exclusive content from NAF.