作者: Petersen, Kenneth A ; Price, Theodore J ; Sankaranarayanan, Ishwarya ; Kume, Moeno ; Munro, Gordon ; Mwirigi, Juliet M ; Madsen, Torsten M ; He, Lucy ; Tavares-Ferreira, Diana

Chemotherapy-induced peripheral neuropathy is a challenging condition to treat, and arises due to severe, dose-limiting toxicity of chemotherapeutic drugs such as paclitaxel. This often results in debilitating sensory and motor deficits that are not effectively prevented or alleviated by existing therapeutic interventions. Recent studies have demonstrated the therapeutic effects of Meteorin, a neurotrophic factor, in reversing neuropathic pain in rodent models of peripheral nerve injury induced by physical trauma. Here, we sought to investigate the potential antinociceptive effects of recombinant mouse Meteorin (rmMeteorin) using a paclitaxel-induced peripheral neuropathy model in male and female mice. Paclitaxel treatment (4 × 4 mg/kg, i.p.) induced hind paw mechanical hypersensitivity by day 8 after treatment. Thereafter, in a reversal dosing paradigm, five repeated injections of rmMeteorin (.5 and 1.8 mg/kg s.c. respectively) administered over 9 days produced a significant and long-lasting attenuation of mechanical hypersensitivity in both sexes. Additionally, administration of rmMeteorin ( .5 and 1.8 mg/kg), initiated before and during paclitaxel treatment (prevention dosing paradigm), reduced the establishment of hind paw mechanical hypersensitivity. Repeated systemic administration of rmMeteorin in both dosing paradigms decreased histochemical signs of satellite glial cell reactivity as measured by glutamine synthetase and connexin 43 protein expression in the dorsal root ganglion. Additionally, in the prevention administration paradigm rmMeteorin had a protective effect against paclitaxel-induced loss of intraepidermal nerve fibers. Our findings indicate that rmMeteorin has a robust and sustained antinociceptive effect in the paclitaxel-induced peripheral neuropathy model and the development of recombinant human Meteorin could be a novel and effective therapeutic for chemotherapy-induced peripheral neuropathy treatment. PERSPECTIVE: Chemotherapy neuropathy is a major clinical problem that decreases quality of life for cancer patients and survivors. Our experiments demonstrate that Meteorin treatment alleviates pain-related behaviors, and signs of neurotoxicity in a mouse model of paclitaxel neuropathy.

2019-08-01·Pain1区 · 医学

Antihyperalgesic effects of Meteorin in the rat chronic constriction injury model: a replication study

1区 · 医学

Article

作者: Xie, Jennifer Y ; Petersen, Kenneth A ; Porreca, Frank ; Munro, Gordon ; Qu, Chaoling

Abstract:

Data from preclinical research have been suggested to suffer from a lack of inherent reproducibility across laboratories. The goal of our study was to replicate findings from a previous report that demonstrated positive effects of Meteorin, a novel neurotrophic factor, in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Notably, 5 to 6 intermittent subcutaneous (s.c.) injections of Meteorin had been reported to produce reversal of mechanical allodynia/thermal hyperalgesia after injury, wherein maximum efficacy of Meteorin was reached slowly and outlasted the elimination of the compound from the blood by several weeks. Here, we evaluated the efficacy of Meteorin in reversing hindpaw mechanical hyperalgesia and cold allodynia in male, Sprague-Dawley rats with CCI. Nociceptive behavior was monitored before and after CCI, and after drug treatment until day 42 after injury. Systemic administration of recombinant mouse Meteorin (0.5 and 1.8 mg/kg, s.c.) at days 10, 12, 14, 17, and 19 after CCI produced a prolonged reversal of neuropathic hypersensitivity with efficacy comparable with that obtained with gabapentin (100 mg/kg, orally). Despite some protocol deviations (eg, nociceptive endpoint, animal vendor, testing laboratory, investigator, etc.) being incurred, these did not affect study outcome. By paying careful attention to key facets of study design, using bioactive material, and confirming drug exposure, the current data have replicated the salient findings of the previous study, promoting confidence in further advancement of this novel molecule as a potential therapy for neuropathic pain.

2012-10-01·Experimental neurology2区 · 医学

Meteorin reverses hypersensitivity in rat models of neuropathic pain

2区 · 医学

Article

作者: H. Moore Arnold ; Jesper Roland Jørgensen ; Bang Jian Gong ; Carol Huang ; Blake Pepinsky ; Jing-Xia Hao ; Zsuzsanna Wiesenfeld-Hallin ; Teit E. Johansen ; Gordon Munro ; Lars U. Wahlberg ; Xiao-Jun Xu

Neuropathic pain is caused by a lesion or disease to the somatosensory nervous system and current treatment merely reduces symptoms. Here, we investigate the potential therapeutic effect of the neurotrophic factor Meteorin on multiple signs of neuropathic pain in two distinct rat models. In a first study, two weeks of intermittent systemic administration of recombinant Meteorin led to a dose-dependent reversal of established mechanical and cold hypersensitivity in rats after photochemically-induced sciatic nerve injury. Moreover, analgesic efficacy lasted for at least one week after treatment cessation. In rats with a chronic constriction injury (CCI) of the sciatic nerve, five systemic injections of Meteorin over 9 days dose-dependently reversed established mechanical and thermal hypersensitivity as well as weight bearing deficits taken as a surrogate marker of spontaneous pain. The beneficial effects of systemic Meteorin were sustained for at least three weeks after treatment ended and no adverse side effects were observed. Pharmacokinetic analysis indicated that plasma Meteorin exposure correlated well with dosing and was no longer detectable after 24 hours. This pharmacokinetic profile combined with a delayed time of onset and prolonged duration of analgesic efficacy on multiple parameters suggests a disease-modifying mechanism rather than symptomatic pain relief. In sciatic nerve lesioned rats, delivery of recombinant Meteorin by intrathecal injection was also efficacious in reversing mechanical and cold hypersensitivity. Together, these data demonstrate that Meteorin represents a novel treatment strategy for the effective and long lasting relief from the debilitating consequences of neuropathic pain.

项与 Recombinant human meteorin (Hoba Therapeutics) 相关的新闻（医药）

2024-05-09

·Pharmaceutical Technology

Novo Holdings-backed Commit launches with $17.2m in seed funding

Commit was initially incubated at the BioInnovation Institute in Denmark, which receives funding from the Novo Nordisk Foundation. Image Credit: Andrzej Rostek / Getty Images. Commit Biologics has emerged from stealth with €16m ($17.2m) in seed money to develop antibody therapies to treat cancer and autoimmune diseases using its bispecific complement engaging (BiCE) platform. The lead investors included Novo Nordisk ’s holding and investment company, Novo Holdings, along with European venture capital firm, Bioqube Ventures. The Danish biotech was founded in 2021 as a spinout from Aarhus University and was initially incubated at the BioInnovation Institute in Denmark, which receives funding from the Novo Nordisk Foundation. Commit CEO, Krishna Polu explained the workings of its platform: “Our BiCE platform gives us the ability to engage the complement system so that it attacks targeted cells in a highly selective manner.” “This platform also means we can use established antibodies, which cuts development times and reduces risk, to develop best-in-class therapeutics. This is a novel way of harnessing the immune system to tackle cancer and autoimmune disease, and we are confident in the tremendous potential it offers.” Antibody therapies, including antibody drug conjugates (ADCs), have been an area of interest in recent years and have seen multiple high-value deals. In October 2023, Merck & Co signed a licencing deal for three ADC therapies with Daiichi Sankyo worth up to $22bn. See Also: GHIT Fund invests Y1.54bn in malaria and NTD drug projects BridgeBio Oncology Therapeutics launches with $200m funding In November 2023, AbbVie purchased ADC specialist ImmunoGen for $10.1bn. The US pharma giant doubled down on investments in this area and signed a $375m deal with BigHat Biosciences to identify and develop antibody therapies, in December 2023. As per Commit, its BiCE platform can potentially decrease the conventional limitations of antibody therapies such as toxicities, specific target density considerations, and T-cell exhaustion (in the case of T-cell therapies). In December 2023, Novo Holdings invested in another Danish startup , Hoba Therapeutics. The company’s lead candidate is non-opioid therapy, a recombinant human meteorin HB-086. Other candidates in Hoba’s pipeline include HP-086 and HP-097, both of which are being developed to treat hearing loss.

并购抗体药物偶联物

2023-12-11

·PRNewswire

Hoba Therapeutics raises EUR 23 million in a Series A to advance new drug candidate against chronic neuropathic pain

COPENHAGEN, Denmark, Dec. 11, 2023 /PRNewswire/ -- Hoba Therapeutics, a Novo Holdings-founded Danish biotech company dedicated to developing novel therapeutic proteins for patients living with chronic neuropathic pain and hearing loss, today announced that it has raised EUR 23 million (USD 25 million) in a Series A financing first close. The financing was co-led by Indaco Venture Partners and Medical Incubator Japan, and includes investments from current investors Novo Holdings, Eir Ventures, and the Export and Investment Fund of Denmark (EIFO). In the syndicate is also The European Innovation Council Fund with an investment as part of the Accelerator funding program under Horizon Europe. Hoba Therapeutics is developing HB-086 for the treatment of chronic neuropathic pain conditions. Neuropathic pain represents a significant unmet medical need, affecting more than 400 million patients worldwide. HB-086 is a non-opioid compound with a unique mode of action, targeting the underlying cause in the peripheral nervous system to reverse neuropathic pain. A comprehensive preclinical data package demonstrated a fast onset and long-acting analgesic effect, and also the ability to prevent the development of neuropathic pain. The proceeds of the Series A first close will enable Hoba Therapeutics to advance HB-086 through late pre-clinical development to the completion of Phase 1 clinical studies in patients for painful Chemotherapy-Induced Peripheral Neuropathy (CIPN). The indication is selected as a gateway indication into chronic neuropathic pain disorders and is a painful, often debilitating condition caused by cancer treatment with certain chemotherapy drugs. "We are thrilled to close the first round of the Series A," said Torsten M. Madsen, CEO of Hoba Therapeutics. "This is an experienced investor syndicate backing Hoba Therapeutics. In addition to the participation of our current investors, we have strengthened the syndicate with the participation of funds from Europe and Japan, along with strong support from The European Innovation Council Fund. This shows the shared perspective on the large unmet need we aim to fill and reflects our focus and commitment to help patients worldwide and we believe that these funds can contribute significantly to achieving our objectives." "Indaco is proud to have led this Series A round, together with Medical Incubator Japan, and we are excited to join Hoba Therapeutics as an investor," added Goncalo Rebelo de Andrade, Partner at Indaco BIO Fund. "At Indaco, we give priority to companies that, like Hoba Therapeutics, are aimed at tackling the underlying causes of disease and are led by high-profile committed teams. In advancing pioneering pharmaceutical solutions, the leadership team at Hoba Therapeutics exhibits extraordinary expertise and commitment. While focusing firmly on both scientific excellence and patient benefit, they are well-positioned to make a substantial impact in healthcare." Camilla Petrycer Hansen, Principal, Seed Investments, Novo Holdings, said: "As a founding investor, we are excited about the prospects of Hoba Therapeutics. A staggering number of people globally endure the debilitating consequences of chronic pain every day, a vast issue largely neglected by the market due to a dearth of innovation in this field for many years. This unmet need is not only a burden for patients but also imposes significant costs on healthcare systems. Together with Eir Ventures and EIFO, we are delighted to welcome new investors into our syndicate, firmly believing in their substantial contribution to the continued progress of Hoba Therapeutics." Dr. Kenji Harada, Investment Officer at Medical Incubator Japan, expressed his excitement about the investment in Hoba, a Danish innovation: "It's a great honour for us to take a co-lead position in this round. I firmly believe that Hoba Therapeutics' programs will yield significant positive impacts on pain management and related therapies. This investment in an outstanding Danish company not only signifies our support, but also paves the way for future investments from Japan into Danish and other European biotech companies." Svetoslava Georgieva, Chair of the EIC Fund Board, said: "The EIC Fund has established itself as a strong force in EU deep-tech investments. This unique form of financing via EIC – combining grants and equity – is proving itself highly attractive to Europe's most promising start-ups. Our investment will provide Hoba Therapeutics with means to help patients suffering from chronic neuropathic pain worldwide." About chronic neuropathic pain Chronic neuropathic pain is a significant global health issue, affecting a substantial portion of the population worldwide. In Europe, the prevalence is estimated to be 6–8%[1] of the general population. Chronic neuropathic pain represents an enormous personal and economic burden. Neuropathic pain is a chronic disorder resulting from damage or dysfunction of the nervous system. Causative factors are lesions in or disorders of the nervous system, such as injury, pressure, toxic agents (e.g., chemotherapy), viral infections, and metabolic disorders. These lesions lead to aberrant functioning of sensory nerve cells, resulting in a chronic, debilitating sensation of pain. Chronic neuropathic pain is primarily managed with antidepressants (including TCAs, SSRIs, and SNRIs), antiepileptic drugs like pregabalin and gabapentin, and opioids. These medications modify pain perception and stabilise nerve cells, but their effectiveness varies widely among individuals, and they often fail to provide complete pain relief. Side effects, such as dizziness, tiredness, and addiction risks are major concerns. A major limitation is that these drugs generally don't target the specific causes of neuropathic pain, and their efficacy is reduced when the underlying conditions, like nerve damage, cannot be treated effectively[2],[3]. The complexity and variability of chronic neuropathic pain necessitates a multifaceted treatment approach and highlights the need for ongoing research and development of more effective and safer treatment options. The global neuropathic pain market is estimated to be valued at USD 7.6 billion in 2023 and is expected to exhibit a CAGR of 6.2% during the next seven years[4]. About Hoba Therapeutics Hoba Therapeutics is a Danish biotech developing restorative treatments for chronic pain disorders and hearing loss. Both indications have a clear unmet medical need for safe and efficacious treatments for millions of patients worldwide. Hoba Therapeutics is developing HB-086 for the treatment of chronic neuropathic pain. HB-086 is a non-opioid compound with a unique mechanism of action targeting the peripheral nervous system to reverse neuropathic pain and the underlying cause of the disease. The second drug candidate HB-097 is a pharmacological treatment for sensorineural hearing loss. Preclinical data of HB-097 show both a preventive effect of hearing loss by protecting nerve cells and a regenerative effect by reversal of already induced damage. Hoba Therapeutics was founded in 2016 by Novo Holdings and Borean Innovation. Hoba Therapeutics received the Accelerator grant from the European Innovation Council in 2021 and the Grand Solution grant from Innovation Fund Denmark in 2018. About Novo Holdings A/S Novo Holdings is a holding and investment company that is responsible for managing the assets and the wealth of the Novo Nordisk Foundation. The purpose of Novo Holdings is to improve people's health and the sustainability of society and the planet by generating attractive long-term returns on the assets of the Novo Nordisk Foundation. Wholly owned by the Novo Nordisk Foundation, Novo Holdings is the controlling shareholder of Novo Nordisk A/S and Novozymes A/S and manages an investment portfolio with a long-term return perspective. In addition to managing a broad portfolio of equities, bonds, real estate, infrastructure, and private equity assets, Novo Holdings is a world-leading life sciences investor. Through its Seeds, Venture, Growth, and Principal Investments teams, Novo Holdings invests in life science companies at all stages of development. As of November 2023, Novo Holdings had total assets of EUR 150 billion. About The Export and Investment Fund of Denmark The Export and Investment Fund of Denmark (EIFO) is the national promotional bank and export credit agency of Denmark combined in one financial institution. EIFO provides a single point of access for Danish companies as well as for their foreign and domestic business partners who need risk-tolerant government capital. EIFO wants to support the successful businesses which can grow the Danish economy and green the globe. We make the world Denmark's business. About Eir Ventures Eir Ventures I AB is a Nordic life science venture capital fund that invests in private companies with outstanding entrepreneurs developing transformative therapeutic approaches. The fund commenced its investment activities in 2020 and invests in opportunities addressing significant unmet medical needs for new therapies, medical technology, and digital health. Eir Ventures AB is led by a team of experienced life science investors and is supported by a strong investor syndicate consisting of leading local and international institutional investors and, uniquely, leading Nordic universities. About Indaco Venture Partners Indaco Venture Partners SGR is one of the largest independent Italian venture capital asset management companies, with over EUR 350 M in assets under management, focused on companies that innovate in electronics, robotics, new materials, medtech, biotech – pharma and digital. Indaco Bio Fund (around EUR 100 M) is exclusively dedicated to investing in the development of innovative pharmacological therapies, across all therapeutic indications but with particular attention to Oncology, CNS, Ophthalmology, Metabolic diseases, Virology, and Infectious diseases. Indaco is focused on the Italian Biotech sector with select investments in other European countries, USA, Canada, and Israel. About Medical Incubator Japan Medical Incubator Japan is a venture capital firm based in Japan specialising in investments within the biotech sector across the EU, Japan, and the US. Their investment portfolio encompasses pharmaceuticals, medical devices, diagnostics, and cutting-edge life science technologies driven by AI. Although their history is relatively concise, they currently manage approximately USD 50 M in assets. Medical Incubator Japan is on the brink of commencing investments from their newly established fund shortly. About The European Innovation Council Fund The European Innovation Council Fund from the European Commission is an agnostic Fund: it invests across all technologies and verticals, and all EU countries and countries associated to Horizon Europe. It provides the investment component of the EIC Accelerator blended finance. The European Investment Bank acts as investment adviser to the EIC Fund. The EIC Fund aims to fill a critical financing gap and its main purpose is to support companies in the development and commercialisation of disruptive technologies, bridging with and crowding in market players, and further sharing risk by building a large network of capital providers and strategic partners suitable for co-investments and follow-on funding. The Fund pays particular attention to the empowerment and support of female founders as well as the ambition to reduce the innovation divide among EU countries. Hoba Therapeutics ApS Ole Maaløes vej 3 Copenhagen DK-2200 [1] Neuropathic Pain: The Scope of the Problem - PMC (nih.gov) [2] Neuropathic pain in adults: pharmacological management in non-specialist settings - NCBI Bookshelf (nih.gov) [3] Pharmacotherapy for Neuropathic Pain: A Review - PMC (nih.gov) [4] "Neuropathic Pain Market Analysis" by Coherent Market Insights SOURCE Hoba Therapeutics

临床1期

100 项与 Recombinant human meteorin (Hoba Therapeutics) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
三叉神经痛	临床前	丹麦	Hoba Therapeutics ApS初创企业	2023-11-24
神经痛	临床前	丹麦	Hoba Therapeutics ApS初创企业	-
亨廷顿舞蹈病	药物发现	丹麦	NsGene A/S	-