MitoRx demonstrates mitochondrial therapy holds potential for weight loss

Mitochondrial-targeted sulfide donor therapy shows metabolic disease promise, reducing weight gain and protecting against muscle loss in mice.

British mitochondrial therapeutics developer MitoRx Therapeutics has published the results of a study that demonstrates the potential of its approach to address obesity. The study showed that one of the company’s mitochondrial-targeted sulfide donor (mtH2SD) drugs significantly slowed the rate of gain in weight of mice on a high-fat diet while also protecting against muscle loss.

Published today in Pharmacological Research, the study involved preclinical trials in mice with high-fat diet (HFD)-induced obesity, in what MitoRx claims is the first comprehensive research of its kind to explore mitochondrial sulfide donors as a therapeutic strategy for obesity and its related conditions. Results revealed that treatment with the company’s AP39 compound slowed the rate of weight gain by 32% compared to controls.

“Having comprehensively demonstrated that mitochondrial-targeted sulfide donors alleviate weight gain and significantly reduce multiple markers of obesity, we mark the beginning of a new era in the development of an innovative therapeutic approach for metabolic disease through the modulation of mitochondrial sulfide-signalling,” said the paper’s lead author, Dr Aneta Stachowicz, from Jagiellonian University Medical College in Poland.

MitoRx, which had been primarily focused on mitochondrial treatments for myopathies, led by Duchene Muscular Dystrophy (DMD), is now also applying its platform to obesity. The company is developing next generation mtH2SD treatments that offer anti-obesity effects without the detrimental side effects of muscle loss, with plans to enter clinical trials in around two years’ time.

My take on this: We’ve been following progress at MitoRx closely since it first emerged in 2022. Licensing IP developed by University of Exeter Professor Matt Whiteman, the company is developing a pipeline of mitochondrial-protective therapeutics with potential in multiple age-related diseases, but its work in obesity is something new.

Hydrogen sulfide is known to play a crucial role in liver function, particularly in regulating lipid metabolism and mitochondrial processes. However, until this study, MitoRx says its direct delivery to mitochondria as a possible treatment for metabolic disorders had not been fully explored. We caught up with CEO Dr Jon Rees to find out more.

The recent study showed that AP39 not only reduced weight gain but also mediated substantial reductions in liver steatosis, triglycerides, de novo lipogenesis and inflammatory markers. Moreover, it downregulated key liver proteomic markers associated with weight gain and obesity development, particularly through pathways implicated in lipid synthesis and storage.

“In obesity, the hormonal response to mealtimes is blunted,” says Rees. “It’s been demonstrated independently of us that restoring sulfide signaling restores glucose-responsive GLP-1 release. So, it appears the hormonal response to mealtimes in general requires functional sulfide signaling, which we restore. Effectively, we’re putting the pathway back into order.”

Discover more about the study, including how it helps protect against muscle loss and its potential in both combination and single treatments, with insights straight from Dr Jon Rees HERE.

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