University of Debrecen

Novo Nordisk continues to list monlunabant in its midstage diabetes and obesity pipeline.\n Novo Nordisk’s cannabinoid CB1 receptor blocker has run into another problem. Months after sharing obesity data that left investors underwhelmed, the Danish drugmaker has reported the failure of a midphase diabetic kidney disease trial of the molecule.CB1 receptor blockade is an old idea—Sanofi won approval for a drug with the mechanism in 2006—but Novo identified Inversago Pharma as a company capable of realizing the potential of the approach. Novo acquired the Canadian biotech in a deal worth up to $1.1 billion in 2023. Since then, a mix of lackluster efficacy and concerning safety signals for monlunabant in obesity have taken the shine off the deal.The program took another hit Wednesday when Novo reported a phase 2 flop. Investigators randomized 254 diabetic kidney disease patients to receive one of two doses of monlunabant or placebo. After 16 weeks of once-daily dosing, people on the study drug did no better than their counterparts on placebo on a measure of kidney function. The result caused the trial to miss its primary endpoint.Reporting of mild to moderate neuropsychiatric side effects was more frequent with monlunabant than placebo. The safety data add to concerns that the molecule suffers from some of the same problems that held back CB1 blockers in the past. European authorities withdrew the approval of Sanofi’s CB1 obesity drug in 2009 after studies found it doubled the risk of psychiatric disorders. Novo is yet to share safety and efficacy data from the kidney disease trial, with the only other snippet in the disclosure being the detail that the most common adverse events were gastrointestinal and the vast majority of cases were of mild to moderate severity.Martin Holst Lange, M.D., Ph.D., the company’s executive vice president of development, told analysts on its financial call Wednesday morning that Novo wasn’t discouraged by the fail, pointing out that “we never did the acquisition of monlunabant to develop it purely for diabetic kidney disease—our focus was on the weight loss potential.”“Second, I just remind you that that that these are small studies, so obviously, we try to see them in the context of the full picture,” he said. “When we look at the safety and tolerability profile, it was comparable, albeit at a slightly lower rate than in the dedicated obesity study, basically indicating that we can still have an aspiration of exploring this further in phase 2b with lower doses, looking at weight loss potential, but obviously also—and this has been the intent from the get-go—ruling out a potential safety concern.”

骨骼肌是损伤后少数能够完全再生的器官之一。尽管骨骼肌干细胞卫星细胞(SC)在再生过程中至关重要，但其激活和分化需要与损伤部位存在或出现的各种细胞类型持续相互作用。 骨骼肌是损伤后少数能够完全再生的器官之一。尽管骨骼肌干细胞卫星细胞(SC)在再生过程中至关重要，但其激活和分化需要与损伤部位存在或出现的各种细胞类型持续相互作用。再生过程始于肌纤维的退化，释放各种危险相关分子(DAMPs)，这些分子可被骨骼肌组织内的细胞识别。 浸润性炎性ly6high MΦs是细胞清除的主要参与者，并释放进一步的促炎细胞因子，促进SC增殖所需的炎症环境。炎症在骨骼肌再生中起着决定性的作用，抑制炎症会完全破坏肌肉修复。 图片来源： https://doi-org.libproxy1.nus.edu.sg/10.1038/s41419-023-06228-7 近日，来自德布勒森大学的研究者们在Cell Death Dis.杂志上发表了题为“Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury”的文章，该研究表明抑制A3Rs可能对损伤后骨骼肌再生具有治疗价值。 骨骼肌再生是一个复杂的过程，由多个相互作用的步骤编排。越来越多的报道表明，炎症反应在将初始肌肉损伤反应与损伤后的及时肌肉再生联系起来方面起着核心作用。核苷腺苷长期以来一直被认为是一种内源性抗炎分子，在组织损伤期间大量产生。它通过四种腺苷受体介导其生理作用。由此可见，腺苷A3受体(A3Rs)不通过骨骼肌表达，但存在于各种炎症细胞的表面。 本文研究了A3Rs缺失对心脏毒素损伤小鼠胫骨前肌(TA)再生的影响。在这里，研究者报道了A3R - / -小鼠骨骼肌再生的特点是更强的初始炎症反应，导致更多的炎症细胞迁移到损伤部位，更快地清除细胞碎片，增强卫星细胞(肌肉干细胞)的增殖和更快的分化，并增加了生成的成肌细胞的融合。这导致加速骨骼肌组织修复和形成更大的肌纤维。 虽然浸润性免疫细胞表达A3Rs，并在损伤的A3R - / -肌肉中表现出增加的炎症特征，但骨髓移植实验表明，组织常驻细胞对组织损伤的反应增加是观察到的现象的原因。总之，该数据表明，A3Rs是损伤相关再生炎症的负调节因子，因此也是TA肌肉纤维生长的负调节因子。 ctx诱导损伤后A3R+/+和A3R - / -小鼠TA肌肉的时间依赖性组织学形态 图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1038/s41419-023-06228-7 综上所述，A3Rs是损伤相关再生炎症的负调节因子，因此也是TA肌肉纤维生长的负调节因子。因此，抑制A3Rs可能对损伤后骨骼肌再生具有治疗价值。(生物谷 Bioon.com） 参考文献 Nastaran Tarban et al. Cell Death Dis. Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury. 2023 Oct 28;14(10):706. doi: 10.1038/s41419-023-06228-7.

More than 1 million Hungarians could experience tinnitus Tinnitus Klinika's 3 clinics will provide Lenire throughout Hungary Availability in Hungary follows publication of second large-scale clinical trial results, showing greater improvement in tinnitus symptoms BUDAPEST, Hungary, Sept. 29, 2022 /PRNewswire/ -- Irish medical device company, Neuromod Devices Ltd., which specialises in the treatment of tinnitus, has reached an agreement with Tinnitus Klinika kft, a provider of specialist tinnitus care, to make its Lenire device available in Hungary. Continue Reading Tamás Nagy, CEO & Owner of Tinnitus Klinika Tinnitus patient using Lenire Lenire is a bimodal neuromodulation device which has shown in analysis of real-world patients and multiple large-scale clinical trials to reduce the severity of tinnitus symptoms. Tinnitus, commonly known as "ringing in the ears", is a complex neurological condition resulting in the perception of sound without an external source. Landmark research into the prevalence of tinnitus in Europe was published in renowned scientific journal, The Lancet, in late 2021. It found that prevalence of any tinnitus was 14.7%i, which could mean that 1.4 million Hungarians experience the condition. Through this distribution agreement, Tinnitus Klinika's specialist team has exclusive licence from Neuromod to provide Lenire throughout Hungary to suitable patients for the treatment of their tinnitus. "I'm delighted to work with Tinnitus Klinika to make Lenire available to people living with tinnitus in Hungary. Tinnitus is globally recognised as a significant healthcare challenge and many people living with the condition have unmet clinical needs. Tinnitus specialists like Tinnitus Klinika deeply understand the needs of tinnitus patients and we're proud to be able to support them in improving therapeutic outcomes for their patients," explains Dr Ross O'Neill, Founder and CEO of Neuromod Devices. In the last 12 months Neuromod has expanded availability of Lenire in Europe, launching it in Denmark, Norway, Spain, Switzerland, and the UK. Earlier in 2022 the results of an independent real-world analysis were published in the peer-reviewed scientific journal, Brain Stimulation, demonstrating the safety and efficacy of the Lenire device for improving symptoms in tinnitus patients. The study found that 85% of tinnitus patients experienced a reduction in their tinnitus symptoms, as measured by THIii, following six to 12 weeks of treatment using Lenireiii. The device has also been used in large-scale clinical trials with over 500 patients. In June, the results of Lenire's second large-scale clinical trial were published in the highly regarded scientific journal, Nature – Scientific Reports. They showed a significant further breakthrough for improving tinnitus symptoms severity with Lenireiv. By changing the stimuli patients received halfway through their treatment plan, a clinically significant greater average improvement in tinnitus symptom severity was demonstratediv. 95% of treatment-compliant participants reported an improvement in their tinnitus symptoms, as measured by THIii,iv. 91% of treatment-compliant participants reported an improvement which sustained at least up to 12 months after treatment had endediv. Tinnitus Klinika's team have been providing specialist care for people living with tinnitus since it was founded in 2008 by Tamás Nagy, who holds a degree in Audiology from Oxford-Brookes University. The organisation operates 3 clinics in Hungary at Czeizel Institute in Budapest, Hallomás Center in Veszprém, and at Debrecen University in partnership with the University's Medical school. Tinnitus Klinika offers a suite of therapeutic interventions for people with tinnitus, which now includes Lenire, and has facilitated research of these interventions in their clinical practices under the guidance of the organisation's Advisory Board. "Tinnitus Klinika's partnership with Neuromod is a significant step forward for our tinnitus patients. I'm delighted to be able to provide an evidence-based treatment option that has seen encouraging patient outcomes in large-scale clinical trials and in the real world as part our suite of services for people living with the condition. I'm looking forward to working closely with Neuromod's team to achieve the best possible patient outcomes in our clinics ," explains Tamás Nagy, CEO at Tinnitus Klinika. Lenire is a bimodal neuromodulation device which combines mild electrical pulses to the tongue with sound stimulation to drive neuroplasticity in the brain which reduces the symptoms of tinnitus. It has CE-mark certification for the treatment of tinnitus under the supervision of an appropriately qualified healthcare professional and is currently available throughout Europe. The device consists of Bluetooth® headphones which play customised sounds to activate the auditory nerve, a proprietary intra-oral device which provides mild electrical stimulation to the surface of the tongue, known as a Tonguetip®, and a controller which controls the duration and intensity of treatment with the device. The device's sound and electrical stimuli can be calibrated to suit a patient's tinnitus after an initial assessment of their condition which includes an audiological exam. The supervising healthcare professional demonstrates how to use the device and provides the patient with instructions for use. Subsequently, patients use Lenire for 60 minutes per day typically for at least 10 weeks. Follow-up visits with the healthcare professional occur during treatment to monitor patients' progress. At the end of the prescribed treatment plan, the healthcare professional advises the patient about their continued use of Lenire. For more information please contact: Neil Doyle Global Director of Marketing, Neuromod Devices [email protected] About Neuromod Devices Ltd Founded in 2010, Neuromod Devices Ltd. is a medical technology company headquartered in Dublin, Ireland. Neuromod specialises in the design and development of neuromodulation technologies to address the clinical needs of underserved patient populations who live with chronic and debilitating conditions. The lead application of Neuromod's technology is in the field of tinnitus, where Neuromod has completed extensive clinical trials to confirm the efficacy of its non-invasive neuromodulation platform in this common disorder. Neuromod's tinnitus treatment device, Lenire, is currently available throughout Europe. For more information visit . About Tinnitus Klinika kft Tinnitus Klinika kft, established in 2008, is a provider of specialist tinnitus care operating 3 clinics throughout Hungary at Czeizel Institute in Budapest, Hallomás Center in Veszprém, and at Debrecen University. Tinnitus Klinika provides a range of treatment interventions for people living with tinnitus. About Lenire Lenire is the first non-invasive bimodal neuromodulation tinnitus treatment device shown to soothe and relieve tinnitus in a large-scale clinical trial. Lenire has CE-mark certification for the treatment of tinnitus under the supervision of an appropriately qualified healthcare professional in Europe. Further details about Lenire including a list of providers can be found at . References (i) R. Biswas et al., Tinnitus prevalence in Europe: a multi-country cross-sectional population study, The Lancet Regional Health (2021), (ii) THI or Tinnitus Handicap Inventory is a clinical standard for measuring the impact of tinnitus on someone's day-to-day life. Measured on a scale of 100, the higher the score, the greater the impact of tinnitus. Reducing a person's THI score should correspond to improved quality of life by reducing how their tinnitus is affecting them. (iii) Buechner A, Lesinski-Schiedat A, Becker P, Lenarz T, Real-world clinical experience with bimodal neuromodulation for the treatment of tinnitus - A case series, Brain Stimulation (2022), doi: . (iv) Conlon et al., Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial, Sci Rep, (2022) Photo: Photo: SOURCE Neuromod Devices Ltd