Natural Sugar Fructose May Improve DMD Treatment Delivery, Mouse Study Suggests

The natural sugar fructose, commonly found in fruits and vegetables, may improve a type of treatment for Duchenne muscular dystrophy (DMD), according to researchers.

The study, “Fructose Promotes Uptake and Activity of Oligonucleotides With Different Chemistries in a Context-dependent Manner in mdx Mice,” was published in the journal Molecular Therapy – Nucleic Acids.

A therapeutic approach for DMD that delivers small molecules called antisense oligonucleotides to muscle cells has shown promising results in both preclinical and clinical studies.

This therapeutic strategy – called antisense oligonucleotide (AO)-mediated exon-skipping therapeutics – is capable of restoring partial dystrophin production (the protein whose absence causes Duchenne MD).

“Despite the promise, low systemic delivery efficiency remains a critical challenge for therapeutic use of AOs,” researchers wrote. As a result, there is a growing need to find new ways to enhance delivery of AOs to muscle cells.

In this study, following previous results, a team of researchers investigated the role of carbohydrates, one of the main types of nutrients, which include fructose and other sugars.

They used dystrophin-deficient rodents, known as mdx mice, to investigate the effect of fructose alone in enhancing AO delivery to the animals. Researchers observed that fructose significantly increased AO delivery, an effect particularly noticeable with a specific AO, the phosphorodiamidate morpholino oligomer (PMO).

When compared to delivery without fructose, PMO delivery with fructose into mice muscle cells was four times higher. This led to increased production of dystrophin and better recovery of some muscle use.

Exondys 51 (eteplirsen) is the first PMO approved by the U.S. Food and Drug Administration (FDA). The drug is also the first FDA-approved treatment for DMD in the U.S.

“Currently the approved drug has minimal efficacy, and the underlying problem is the morpholino by itself has very limited muscle uptake,” Hong Moulton, at Oregon State University College of Veterinary Medicine and an author of the study, said in a press release.

“If you can get more material into the muscle, then you can have more dystrophin produced. The fructose approach we studied can do that,” Moulton said.

Overall, the researchers concluded, their results show that fructose is a “safe and efficient delivery formulation for enhancing the uptake of different AOs to muscle and can be used as a delivery tool for optimization of AO sequences and backbones.

“Our findings unveil a new role of fructose in drug delivery and might have implications for current exon-skipping clinical trials for DMD,” they wrote.