I’ve been conducting or overseeing scientific research for more than 40 years (yikes!), but I continue to be humbled by its nuances, complexities and ambiguities. Sometimes, just when you think you have something figured out, you find evidence to the contrary. Sometimes, as Vladimir Lenin said, progress is made by taking “one step back, two steps forward.”
The findings reported in a recent research paper from the University of Utah on autosomal dominant Stargardt disease are a great case in point. But before I discuss the new research, which was funded by the Foundation Fighting Blindness, let me give you a little background on this story. One word of warning – as my professional vernacular is loaded with acronyms, I’ll be serving alphabet soup with this post.
Stargardt disease affects approximately 30,000 people in the United States and 40,000 in Europe. A vast majority of the cases, about 95 percent, are autosomal recessive and mainly caused by mutations in the ABCA4 gene.
The other five percent are autosomal dominant, most of which are caused by defects in the gene ELOVL4. This form of disease is often referred to as STGD3. The University of Utah paper is specifically about new findings for ELOVL4 mutations.
In 2001, Foundation-funded researchers found that ELOVL4 was linked to STGD3. They also knew that ELOVL4 was involved in the production of very long chain polyunsaturated fatty acids (VLC-PUFAs), and suspected that a lack of those fatty acids was detrimental to retinal health. Humans get VLC-PUFAs by consuming their precursors, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are abundant in coldwater fish, as well as fish-oil and algal supplements.
In 2007, the University of Utah’s Dr. Paul Bernstein began a clinical trial of DHA and EPA supplementation for people with STGD3 to see if it would slow their vision loss. His observations of a Utah family with ELOVL4 mutations suggest that DHA and EPA supplementation might do so. In 2006, his group published a retrospective analysis, which found that the family members who had most EPA and DHA in their diets had the mildest retinal changes.
But alas, as we seem to be on a logical path forward for treating STGD3, a team of scientists from the University of Utah — which included Drs. David Krizaj, Peter Barabas and Bernstein — found that mice lacking VLC-PUFAs in their photoreceptors did not have retinal degeneration or associated vision loss. It appears to be a classic “one-step back” moment.
Now, these findings come with a major caveat (not to be confused with caviar, which, interestingly, is high in DHA and EPA). This new research is based on mouse models, which are by no means perfect replications of human STGD3.
However, the new study also suggests that ELOVL4 may be involved in something more than the production of VLC-PUFAs, and that “something” may also be linked to STGD3. More Foundation-funded research is underway to get a better picture of what causes STGD3.
Ultimately, Dr. Bernstein’s prospective clinical trial, which will conclude later in 2013, will tell us more about the role of DHA and EPA in STGD3.
In the meantime, comrades, I encourage you to check out my previous blog post on DHA and EPA, which discusses how these healthy fats have exciting potential for treating a wide range of retinal degenerations and other health conditions.
Pictured, above: Dr. David Krizaj (Photo courtesy of Dr. Bryan Jones, retinal neuroscientist at the University of Utah.)