University of Exeter Business School

OXFORD, United Kingdom, Oct. 10, 2024 (GLOBE NEWSWIRE) -- MitoRx Therapeutics (MitoRx), a platform biotechnology company developing novel mitochondrial-targeted sulfide-donor therapeutics (mtH2SD) in obesity-related disorders and myopathies announces a publication in Elsevier’s prestigious biomedical sciences journal Pharmacological Research. The work led by collaborators at Jagiellonian University Medical College showed that in a preclinical mouse study involving high-fat diet (HFD)-induced obesity, the company’s mtH2SD compound AP39, significantly slowed the rate of gain in weight. This is the first comprehensive study designed to test whether mitochondrial sulfide donors could address weight gain and fatty liver (steatosis). Mounting evidence suggests that hydrogen sulfide is an important signalling molecule in the liver, regulating lipid metabolism and mitochondrial function, but its direct delivery to mitochondria had not been investigated as a therapeutic strategy in obesity-related metabolic disorders. This is what the Pharmacological Research paper examined. MitoRx’s CSO, Prof Matt Whiteman, and their Senior Discovery Chemist, Dr. Roberta Torregrossa, with co-inventor Dr. Mark Wood at the University of Exeter are co-authors on the paper. It showed that treatment with AP39 reduced weight gain in animals fed HFD by 32% at the end of the research. (1) AP39 is a versatile mtH2SD tool compound that mediates very large and statistically significant reductions in liver steatosis, large and significant reductions in triglycerides, reductions in de novo lipogenesis, reductions in inflammatory markers, and significant downregulation of known liver proteomic markers of weight gain and the development of obesity, indicating mtH2SD-mediated downregulation mTOR/SREBP-1/SCD1 pathway alleviates obesity. MitoRx is developing undisclosed next-generation mtH2SDs to take to the clinic. Importantly, this modality is both muscle protective including in a severe fibrotic muscle atrophy model and is also anti-obesogenic. With this double therapeutic benefit, MitoRx’s next-gen mtH2SDs could potentially address the loss of lean muscle mass which is a serious side effect of marketed GLP-1 receptor agonist drugs in general, especially with age. This approach could be applicable in sarcopenic (age-related muscle mass and strength loss) obesity while also addressing muscle wasting in obese patients in general. Dr. Jon Rees, Chief Executive Officer of MitoRx, said: “MitoRx is advancing its first-in-class mitochondriotropic platform initially focused on myopathies and is now applying it to obesity offering a small molecule anti-obesogenic which is also muscle protective. This latest publication provides solid pre-clinical evidence that AP39 substantially suppressed the gain of weight in HFD-fed animals, suggesting a new pathway to alleviate obesity, whilst avoiding the muscle wasting side-effects that blight GLP-1 receptor agonist drugs. Powerful international research collaborations like this, with the talented team at Jagiellonian University’s Faculty of Medicine, help speed therapeutic advances to patients.” Dr. Aneta Stachowicz, Department of Pharmacology at the Faculty of Medicine, Jagiellonian University Medical College, Poland, and lead author of the Pharmacological Research paper, said: “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.” Matt Whiteman, Professor of Experimental Therapeutics at the University of Exeter Medical School, UK, and co-author of the study added: We discovered impaired sulfide metabolism in overweight patients with type 2 diabetes in 2010 (2) and we noticed that this impairment was driven by the amount of fat tissue these individuals were carrying; an observation since confirmed by many others. These findings suggested that treating this impairment with mtH2SD could potentially treat diabetes, obesity and complications arising from having too much fat in the body. It is gratifying to now translate those observations toward clinically viable drugs with MitoRx References: (1): Mitochondria-targeted hydrogen sulfide donor reduces fatty liver and obesity in mice fed a high fat diet by inhibiting de novo lipogenesis and inflammation via mTOR/SREBP-1 and NF-Kappa-B signaling pathways. Pharmacological Research 209 (2024):107428https://doi.org/10.1016/j.phrs.2024.107428 (2): Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulphide. Diabetologia 53(8):1722-6 (2010). https://doi.org/10.1007/s00125-010-1761-5 Company Contact (MitoRx) Jon Rees, CEOEmail: jon.rees@mitorxtherapeutics.com Phone: +44(0)7826 556622 Media Contact (Scius Communications for MitoRx) Katja Stout, Managing PartnerEmail: katja@sciuscommunications.com Phone: +44(0)7789 435990 University of Exeter Press Office  +44 (0)1392 722405 or 722062pressoffice@exeter.ac.uk Jagiellonian University Marcin Kubatrzecznik@uj.edu.pl About MitoRx TherapeuticsAt MitoRx our mission is to become the leading global developer of medicines arresting the progression of degenerative diseases driven by mitochondrial dysfunction. We are a preclinical stage biotechnology company developing our first-in-class first-in-target, mitochondriotropic therapeutics in obesity-related indications and myopathies. Located in Harwell, Oxford, we have raised £5.4m seed financing from investors including the UK Innovation & Science Seed Fund, the Fink Family Office, Oxford Technology Management, Empirical Ventures, Wren Capital and Longevitytech.fund, as well as angel investors. For more information visit our website at www.mitorxtherapeutics.com and follow us on LinkedIn. About the University of ExeterThe University of Exeter is a Russell Group university that combines world-class research with high levels of student satisfaction. Exeter has over 30,000 students and sits within the Top 15 universities in The Complete University Guide 2025, and tenth in the world in the Times Higher Education (THE) Impact Rankings. In the 2021 Research Excellence Framework (REF), more than 99% of our research were rated as being of international quality, and our world-leading research impact has grown by 72% since 2014, more than any other Russell Group university.https://www.exeter.ac.uk/ About Jagiellonian University The Jagiellonian University is the oldest higher education institution in Poland and one of the oldest in Europe. It was founded on 12 May 1364 by the Polish king Casimir the Great. The Jubilee year 2014 marked the 650th anniversary of this remarkable event. Since its very beginning, the Jagiellonian University has been an international institution. Today, the Jagiellonian University comprises 16 Faculties, where nearly 4 thousand academic staff conduct research and provide education to over 40 thousand students, within the framework of more than 80 different fields of study. The eminent researchers and state-of-the-art infrastructure make the JU one of the leading Polish scientific institutions, collaborating with major academic centres from all over the world. The Jagiellonian University is also home to about 150 student societies, where young researchers pursue their academic interests and develop friendships with people who share their passion. For more information visit our website at https://en.uj.edu.pl/en.

MONDAY, Sept. 9, 2024 -- Losing weight can help a person with obesity -- especially those with diabetes -- fend off serious infections, new data shows. It's an important finding, since "up to one in three hospitalizations in people with diabetes are for infections and people with diabetes are twice as likely to be hospitalized with infections than the general population. They are also at high risk of readmission," said study co-lead author Rhian Hopkins . She's at the University of Exeter Medical School in the U.K. Hopkins presented the research Saturday in Madrid at the annual meeting of the European Association for the Study of Diabetes (EASD). The new study used data from the ongoing UK Biobank, a database that includes health info on almost 500,000 Britons. According to the data, about 64,000 had been hospitalized for a bacterial infection (such as a urinary tract infection or pneumonia); almost 15,000 had been hospitalized with a viral infection (such as the flu), and about 408,000 had never been hospitalized for infection. Obesity seemed linked to a higher risk for severe infection, the team found. Every 5-point increase in BMI -- for example, from a BMI of 30 (the threshold for obesity) to 35 -- incurred a 30% rise in the risk of a serious bacterial infection and a 32% rise for severe viral infection. These associations were for all people, regardless of whether or not they had diabetes , Hopkins noted. However, because diabetes brings higher risks for infection generally, the findings are particularly important for people with the blood sugar disease, she said. “Infections are a major cause of death and ill health, particularly in people with diabetes," Hopkins said in a EASD news release. "Anyone admitted to hospital with a severe infection is also at high risk of being admitted again with another." “This study demonstrates that higher BMI is a cause of hospital admission with infection," she added. "Clinicians could discuss weight-loss options for people with a high BMI at risk of severe infections and readmission to hospital for infection.” Because these findings were presented at a medical meeting, they should be considered preliminary until published in a peer-reviewed journal. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Scientists have discovered a new cause of why people who lack a specific blood group are genetically predisposed to be overweight or obese. Scientists have discovered a new cause of why people who lack a specific blood group are genetically predisposed to be overweight or obese. A team of international researchers, led by the University of Exeter, discovered that people with a genetic variant that disables the SMIM1 gene have higher body weight because they expend less energy when at rest. SMIM1 was only identified 10 years ago, whilst searching for the gene encoding a specific blood group, known as Vel. One in 5,000 people lack both copies of the gene, making them Vel-negative. The findings from the new research suggest that this group is also more likely to be overweight, a conclusion which could one day lead to new treatments. The team now hopes to test whether a cheaply and widely available drug for thyroid dysfunction may be effective in treating obesity in people who lack both copies of SMIM1. The study also found that people without both copies of the gene have other measures linked to obesity including high levels of fat in the blood, signs of fat tissue dysfunction, increased liver enzymes as well as lower levels of thyroid hormones. The new research is published in Med and was funded by the National Institute for Health and Care Research and the British Heart Foundation. The collaboration included partners at the University of Cambridge, the Sanger Institute, the Copenhagen University in Denmark, and the Lund University in Sweden. Lead author Mattia Frontini, Associate Professor of Cell Biology at the University of Exeter Medical School, said: "Obesity rates have nearly tripled in the past 50 years, and by 2030, more than one billion individuals worldwide are projected to be obese. The associated diseases and complications create significant economic burden on healthcare systems. Obesity is due to an imbalance between energy intake and expenditure, often a complex interplay of lifestyle, environmental, and genetic factors. In a small minority of people, obesity is caused by genetic variants. When this is the case, new treatments can sometimes be found to benefit these people -- and we're now hoping to run a clinical trial to find out whether widely-available drug for thyroid supplementation may be beneficial in treating obesity in people who lack SMIM1." "Our findings highlight the need to investigate the genetic cause of obesity, to select the most appropriate and effective treatment, but also to reduce the social stigma associated to it." To make the discovery, the team analysed the genetics of nearly 500,000 participants in the UK Biobank cohort, identifying 104 people with the variant that leads to loss of function in the SMIM1 gene (46 females and 44 males). The team also used the NIHR National BioResource to obtain fresh blood samples from both Vel negative and positive individuals.The NIHR National BioResource worked in partnership with NHS Blood and Transplant (NHSBT) -- which includes more than 100,000 blood donors who signed up to support genetic research studies. Extrapolating the frequencies identified in these cohorts would mean the SMIM1 variant could be a significant factor contributing to obesity for around 300,000 people across the world. The team interrogated the effects they found in four additional cohorts of people with the SMIM1 gene variant. They found that having the variant had an impact on weight, equating to an average extra 4.6kg in females and 2.4kg in males. Co-author Jill Storry, Adjunct Professor at Lund University, Sweden, said: "SMIM1 was only discovered a decade ago, as a long-sought blood group protein on red blood cells, but its other function has remained unknown until now. It's very exciting to find that it has a more general role in human metabolism." Co-author Professor Ole Pedersen, at University of Copenhagen, Denmark, said: "The whole team is very much looking forward to seeing how this new knowledge can be translated into practical solutions for people with this genetic make-up." First author Dr Luca Stefanucci, at the University of Cambridge, said: "With the increased availability of genetic data, and more information on SMIM1 mechanism, we would like to see that when individuals lacking SMIM1 are identified, they receive information and support."