Supplementing N-163 Beta Glucan Shows Disease-Modifying Effects as Adjuvant in Duchenne Muscular Dystrophy

Samuel Abraham, MD, PhD, FRCP, CACR

Findings from a linear, 6-month clinical study of ambulatory and non-ambulatory patients with Duchenne muscular dystrophy (DMD) showed that treatment with an orally consumed ß-glucan food supplement yielded benefit in several outcomes when used along standard of care regimen, including steroids. Above all, the improvements unravel its potential as a disease-modifying therapy adjuvant in DMD.

These data were presented as a late-breaking poster at the 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 19-22, in Dallas, Texas, by lead investigator Samuel Abraham, MD, PhD, FRCP, CACR, Faculty of Medicine, Yamanashi University. At the conclusion of the analysis, Abraham and colleagues recommended a global, multi-centric clinical study to validate this approach as a drug-adjuvant in safely slowing down the progress of DMD.

The study assessed Neu-REFIX, a commercially available beta-glucan food supplement, produced by the N-163 strain of aureobasidium pallulans. It comprised of 24 individuals with DMD, 12 of which were ambulatory, who consumed the ß-glucan food supplement along with standard of care for 6 months, with muscle function assessed by Medical Research Council (MRC) score, 6-minute walk test (6MWT), and North Star Ambulatory Assessment (NSAA).

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After 6 months of treatment, MRC score in the ambulatory group improved in 11 of the 12 individuals, with average improvements of 7.09%. Additionally, 9 of the 12 individuals in this group demonstrated improvements in 6MWT distance, with 29.5 meters of average improvement. Overall 3 patients experienced improvements of 1 unit on NSAA, 1 patient demonstrated a decline by 1 unit, and the remaining ambulatory patients had no change. In the 12 non-ambulatory patients, the MRC score improved in 8 patients by 9.27% and declined in 2 patients.

These data build on previously published findings from a 45-day, open-label study assessing the effects of Neu-REFIX in young patients with DMD. Published in late 2021, the trial included 27 patients with DMD who were divided into groups: controls on steroids (steroid +ve; n = 4), controls not on steroids (steroid -ve; n = 5) and a treatment group of either N-163 ß-glucan supplement along with conventional therapies. Investigators assessed muscle function, disease status, and levels of IL-6, IL-13, tumor necrosis factor-ß (TNF-ß) creatinine kinase (CK), titin, TNF-α, haptoglobin, and dystrophin in the blood and myoglobin in the urine.

Results showed a significant decrease in IL-6 in the N-163 steroid -ve group, from a baseline value of 7.2 (±1.2) pg/ml to 2.7 (±0.03) pg/ml. Additionally, IL-13 decreased in both treatment groups, from 157.76 (±148.68) pg/ml to 114.08 (±81.5) pg/ml among steroid -ve patients and from 289.56 (±232.88) pg/mg to 255.56 (±214.13) pg/ml in the steroid +ve group. Both groups saw an increase of 32% in dystrophin levels. Additionally, 12 of 18 (67%) patients in the treatment group and 4 of 9 (44%) in the control group showed muscle strength improvements on MRC grading.

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REFERENCES
1. Abraham SJK, Raghavan K, Sivakumar T, et al. Late breaking: efficacy of a safe ß-glucan in improving muscle function in Duchenne muscular dystrophy; results of a 6-month nonrandomized open-label extension trial. Presented at: MDA 2023; March 19-22; Dallas, TX. Virtual.
2. Raghavan K, Depeepiya VD, Srinivasan S, et al. Disease-modifying immune-modulatory effects of the N-163 strain of Aureobasidium pullulans produced 1,3-1,6 Beta glucans in young boys with Duchenne muscular dystrophy: results of an open-label prospective, randomized, comparative clinical study. medRxiv. Published online December 14, 2021. doi:10.1101/2021.12.13.21267706