World Duchenne Awareness Day (WDAD) is celebrated every year on the 7th of September. Its aim is to spread awareness of the devastating genetic disorder, Duchenne Muscular Dystrophy (DMD). The first diagnosis of DMD was made over 150 years ago but the first World Duchenne Awareness Day was celebrated in 2014, started by Elizabeth Vroom and Nicoletta Madia of the World Duchenne Organization ^[1-3].

Duchenne muscular dystrophy (DMD) constitutes one of the four muscular conditions called dystrophinopathies. The other three being Becker Muscular dystrophy (BMD, a mild form of DMD); an intermediate clinical presentation between DMD and BMD; and DMD-associated dilated cardiomyopathy (heart-disease) with little or no clinical skeletal, or voluntary, muscle disease ^[4]. DMD is a genetic disorder in which there is progressive muscle degeneration and weakness due to the mutations of the gene that produces a protein called dystrophin that helps keep muscle cells intact. 1 in 5000 boys are affected by DMD. Girls can also be carriers of this disease but are only mildly affected. DMD has no cure. The major mode of therapy has been muscle strengthening exercises and corticosteroid therapy. Gene replacement and exon-skipping therapies to correct the mutations in dystrophin gene are being experimented upon ^[5].

The involvement of Nichi-In Centre for Regenerative Medicine (NCRM) and its sister concern GN Corporation, Japan in DMD started in 2009 with research on biological response modifier glucans (BRMGs) ^[6]. The origin of BRMGs goes back to 1980s when Prof. Noboru Fujii of Miyazaki University discovered a specific strain of a poly extremo-tolerant black yeast Aureobasidium pullulans which secretes a novel exo-polysaccharide Beta 1,3-16 glucans with potent BRMG activities ^[7]. This production was then scaled up from lab-scale to industrial scale in GMP apart from continued research yielding multiple strains with unique produce. The AFO-202 beta glucan produce has been reported to have metabolic balancing potential with regulation of blood glucose ^[8,9] apart from immune enhancement while N-163 beta glucan had abilities to balance the lipid profile, anti-inflammatory properties and immunomodulation ^[10] which GNC and NCRM upon proving with several basic, and pre-clinical studies ^{[11, 12]} undertook a clinical study in young adults with DMD yielding a path breaking outcome ^[13]. The study ^[13] showed that supplementation with N-163 strain produced beta glucan led to a significant decrease in inflammation and fibrosis markers, IL-6, IL-13 and TGF-β apart from increase in blood plasma Dystrophin levels and muscle strength improvement.

The increase in blood plasma dystrophin led us to study the implications. There has been increasingly strong emerging evidence that the primary cause of DMD is a lack of dystrophin in the smooth muscle of blood vessels and not the skeletal or cardiac muscle, as believed for long. The restricted blood supply results in muscle ischemia, injury and fatigue during exercise which leads to fibrosis and progressive muscle damage ^[14,15]. The beta glucans capable of modulating vascular pathology by angiogenesis promotion ^[16], decreasing atherosclerosis by positive effects on lipid metabolism, PPAR agonist action and immune-modulation apart from beneficially modulating the gut bacteria ^{[17, 18]} thus helping on a systemic scale via the gut microbiome-brain axis thus can be an effective and affordable solution to children with DMD ^[19] and muscular dystrophies ^[20] until a full blown effective gene therapy is developed after which it can serve as an effective adjunct..

Given the above background from the September, 2022, we are planning to commemorate the World Duchenne Awareness Day (WDAD) in September with participation from caregivers and parents of children with DMD and conduct a scientific panel discussion by internationally eminent researchers, clinicians, rehabilitation specialists, policy makers, psychiatrists and social workers from all over the world.

A webinar has been planned on 10th September, 2023 to commemorate 2023 Duchenne Awareness day. For registration click here.

(1) https://nationaldaycalendar.com/world-duchenne-awareness-day-september-7/
(2) https://www.duchenneuk.org/world-duchenne-awareness-day-2021/
(3) https://www.worldduchenne.org/
(4) https://rarediseases.info.nih.gov/diseases/6291/duchenne-muscular-dystrophy
(5) https://www.mda.org/disease/duchenne-muscular-dystrophy
(6) www.nichiglucan.com
(7) Ikewaki N, Fujii N, Onaka T, Ikewaki S, Inoko H. Immunological actions of Sophy beta-glucan (beta-1,3-1,6 glucan), currently available commercially as a health food supplement. Microbiol Immunol. 2007;51(9):861-73. doi: 10.1111/j.1348-0421.2007.tb03982.x.
(8) Dedeepiya V, Sivaraman G,Venkatesh A, Preethy S, Abraham S. Potential Effects of Nichi Glucan as a Food Supplement for Diabetes Mellitus and Hyperlipidemia; Preliminary Findings from the Study on Three Patients from India. Case Reports in Medicine 2012 (2012), Article ID 895370; doi:10.1155/2012/895370
(9) Ikewaki N, Sonoda T, Kurosawa G, Iwasaki M, Dedeepiya VD, Senthilkumar R, Preethy S, Abraham SJK. Beta 1,3-1,6 glucans produced by two novel strains of Aureobasidium pullulans exert immune and metabolic beneficial effects in healthy middle-aged Japanese men: Results of an exploratory randomized control study. J Aging Res & Lifestyle 2023;12:61-71. doi: 10.14283/jarlife.2023.11.
(10) Ganesh JS, Rao YY, Ravikumar R, Jayakrishnan AG, Iwasaki M, Preethy S, Abraham S. Beneficial effects of Black yeast derived 1-3, 1-6 beta glucan- Nichi Glucan in a dyslipidemic individual of Indian origin - A case report. J Diet Suppl. 2014;11(1):1-6. doi:10.3109/19390211.2013.859211.
(11) Ikewaki N, Onaka T, Ikeue Y, Nagataki M, Kurosawa G, Dedeepiya VD, Rajmohan M, Vaddi S, Senthilkumar R, Preethy S, Abraham SJK. Beneficial effects of 1,3–1,6 β-glucans produced by Aureobasidium pullulans on non-esterified fatty acid levels in diabetic KKAy mice and their potential implications in metabolic dysregulation. J Diabetes Metab Disord (2022).
(12) Ikewaki N, Raghavan K, Dedeepiya VD, Suryaprakash V, Iwasaki M, Preethy S, senthilkumar R, Abraham SJK. Beneficial immune-regulatory effects of novel strains of Aureobasidium pullulans AFO-202 and N-163 produced beta glucans in Sprague Dawley rats. Clinical Immunology Communications 2021. https://doi.org/10.1016/j.clicom.2021.11.001
(13) Raghavan K, Dedeepiya VD, Srinivasan S, Pushkala S, Subramanian S, Ikewaki N, Iwasaki M, Senthilkumar R, Preethy S, Abraham S. Beneficial immune-modulatory effects of the N-163 strain of Aureobasidium pullulans-produced 1,3-1,6 Beta glucans in Duchenne muscular dystrophy: Results of an open-label, prospective, exploratory case-control clinical study. IBRO Neuroscience Reports 15 (2023) 90-99. DOI : 10.1016/j.ibneur.2023.06.007.
(14) Ito K, Kimura S, Ozasa S, et al. Smooth muscle-specific dystrophin expression improves aberrant vasoregulation in mdx mice. Hum Mol Genet. 2006 Jul 15;15(14):2266-75.
(15) Gajendran N. The root cause of Duchenne muscular dystrophy is the lack of dystrophin in smooth muscle of blood vessels rather than in skeletal muscle per se [version 2; peer review: 3 not approved]. F1000Research 2018, 7:1321. ; https://doi.org/10.12688/f1000research.15889.2
(16) Preethy S, Yamamoto N, Osaza S, Raghavan R, Dedeepiya V, Iwasaki M, Abraham S. Re-examining the therapeutic management of muscular dystrophies from a vascular smooth muscle-centred approach. Journal of Smooth muscle research (In print)
(17) Raghavan K, Dedeepiya VD, Yamamoto N, Ikewaki N, Iwasaki M, Dinassing A, Senthilkumar R, Preethy S, Abraham SJK. Randomised trial of Aureobasidium pullulans-produced beta 1,3-1,6-glucans in patients with Duchenne muscular dystrophy: Favourable changes in gut microbiota and clinical outcomes indicating their potential in epigenetic manipulation. medRxiv 2022.12.09.22283273; doi: 10.1101/2022.12.09.22283273
(18) Preethy S, Ikewaki N, Levy GA, Raghavan K, Dedeepiya VD, Yamamoto N, Srinivasan S, Ranganathan N, Iwasaki M, Senthilkumar R, Abraham SJK. Two unique biological response-modifier glucans beneficially regulating gut microbiota and faecal metabolome in a non-alcoholic steatohepatitis animal model, with potential for applications in human health and disease. BMJ Open Gastroenterology 2022;9:e000985. doi: 10.1136/bmjgast-2022-000985
(19) Samuel JK Abraham, Kadalraja Raghavan, Thanasekar Sivakumar, Sudhakar S Bharathidasan, Subramaniam Srinivasan, Vidyasagar Devaprasad Dedeepiya, Nobunao Ikewaki, Masaru Iwasaki, Rajappa Senthilkumar, Senthilkumar Preethy. Efficacy of a safe ß-glucan in improving muscle function in Duchenne Muscular Dystrophy; results of a 6-month nonrandomized open-label extension trial. MDA Conference 2023.
(20) Kadalraja Raghavan, Thanasekar Sivakumar, Koji Ichiyama, Naoki Yamamoto, Mangaleswaran Balamurugan, Vidyasagar Devaprasad Dedeepiya, Rajappa Senthilkumar, Senthilkumar Preethy, Samuel JK Abraham. Efficacy of N-163 beta-glucan in beneficially improving biomarkers of relevance to muscle function in patients with muscular dystrophies in a pilot clinical study. medrxiv 2023.07.20.23292982v1; doi: 10.1101/2023.07.20.23292982.