Exploring the Therapeutic Potential of Ectoine in Duchenne Muscular Dystrophy: Comparison with Taurine, a Supplement with Known Beneficial Effects in the mdx Mouse

Abstract

Duchenne Muscular Dystrophy (DMD) is a debilitating muscle disorder that condemns patients to year-long dependency on glucocorticoids. Chronic glucocorticoid use elicits many unfavourable side-effects without offering satisfying clinical improvement, thus, the search for alternative treatments to alleviate muscle inflammation persists. Taurine, an osmolyte with anti-inflammatory effects, mitigated pathological features in the mdx mouse model for DMD but interfered with murine development. In this study, ectoine is evaluated as an alternative for taurine in vitro in CCL-136 cells and in vivo in the mdx mouse. Pre-treating CCL-136 cells with 0.1 mM taurine and 0.1 mM ectoine prior to exposure with 300 U/mL IFN-γ and 20 ng/mL IL-1β partially attenuated cell death, whilst 100 mM taurine reduced MHC-I protein levels. In vivo, histopathological features of the tibialis anterior in mdx mice were mitigated by ectoine, but not by taurine. Osmolyte treatment significantly reduced mRNA levels of inflammatory disease biomarkers, respectively, CCL2 and SPP1 in ectoine-treated mdx mice, and CCL2, HSPA1A, TNF-α and IL-1β in taurine-treated mdx mice. Functional performance was not improved by osmolyte treatment. Furthermore, ectoine-treated mdx mice exhibited reduced body weight. Our results confirmed beneficial effects of taurine in mdx mice and, for the first time, demonstrated similar and differential effects of ectoine.

Valorisation of cheese whey for ectoine production by Halomonas neptunia

“…Besides these application areas, ectoine has been shown to be used in relieving mucositis, treating atopic dermatitis, reducing the effect of irradiation and ameliorating the Duchenne Muscular Dystrophy's symptoms (Fondevilla et al 2022;Merckx et al 2022;Alexopoulos et al 2023). This compound has also been demonstrated to be useful in enhancing some industrial processes including the growth of an industrial lactic acid producer bacterium (Tetragenococcus halophila) and an ethanol producer bacterium (Zymomonas mobilis) (Baliarda et al 2003;Zhang et al 2008).…”

New Pharmacological Approaches for Rare Diseases

“…New ongoing therapeutic approaches for treating specific MDs are also discussed for application in myotonic dystrophy type 1 (DM1), the most common form of adult MD, in Duchenne MD [ 3 ], or in limb-girdle MD R1 calpain 3-related (LGMDR1). These strategies explore different drug discovery approaches, including drug repurposing of the antitumor drug vorinostat for DM1 [ 4 ], the potential of natural products such as ectoine or of biologicals such as BLS-M22 for Duchenne MD [ 5 , 6 ], or the validation of glycogen synthase kinase 3β (GSK-3β) as a new therapeutic target for LGMDR1 [ 7 ]. Emerging therapies for other genetic rare diseases such as inherited peripheral neuropathies, collectively called Charcot–Marie–Tooth disease (CMT), are also covered [ 8 ].…”