TDP43

引言 蛋白质的亚细胞定位对蛋白质的功能至关重要，因为它们在不同的细胞区域执行特定的生物学功能。例如，某些蛋白质在细胞核内调控基因表达，而另一些则在细胞质中参与信号传导或物质代谢。这种精确的亚细胞定位是通过复杂的蛋白质转运机制实现的，包括核输入和输出、以及细胞器间的蛋白质运输。蛋白质的异常运输和定位往往与多种疾病的发生发展有关，包括癌症、神经退行性疾病和遗传性疾病等【1,2】。尽管针对性地调控蛋白质的亚细胞定位为治疗这些疾病提供了新的思路，但如何在不干扰细胞其他正常活动的前提下，高效、特异性地控制蛋白质的精确位置，以及如何将这种调控转化为疾病治疗的有效手段，都是该领域所面临的重大科学问题。 通过将目标蛋白与细胞内的穿梭蛋白或锚蛋白耦合来调节其位置，为可编程分子控制提供了另一种途径。为了推进定位控制的理念，以解决导致疾病的蛋白质问题，需要了解使定位被劫持的细胞特征，以及扩展可行的目标蛋白、分子和调控机制的原理。而对定位重编程能力的定量分析也将极大地促进小分子介导的蛋白质重新定位向治疗疾病的应用的扩展。 近日，来自美国斯坦福大学的Steven M. Banik团队在Nature上发表题为Targeted protein relocalization via protein transport coupling的文章，利用一种创新的化学生物学工具——靶向重定位激活分子（TRAM），通过结合穿梭蛋白的转运来控制目标蛋白的亚细胞定位。筛选了一系列具有强效配体的穿梭蛋白，并将其成功用于多种内源蛋白的重新定位。开发了一个定制的成像分析流程，展示了通过分子偶联到含有足够强定位序列的穿梭蛋白，可以调节蛋白质的稳态定位。由此提出了一种通过蛋白质转运重构细胞互作网络的靶向治疗方法，为治疗疾病提供了新的思路。 核定位序列（NLS）和核输出序列（NES）可被karyopherin蛋白家族识别，以调节货物在细胞核和细胞质之间的双向运输。要通过蛋白质运输耦合的方式来克服蛋白质的固有定位，将需要满足2点：（1）在穿梭蛋白上有一个足够强的相反定位序列；（2）穿梭蛋白的必要化学计量比。为此，本文研究人员首先选择了烟酰胺核苷酸腺苷基转移酶1（NMNAT1）作为模型蛋白进行重新定位研究，因为NMNAT1只有一个预测的NLS且没有已知的直接DNA结合域，所以可能容易受到小分子介导的重新定位的影响。为了研究缺乏已知小分子结合位点的蛋白质，研究人员合成了双功能分子TRAM 1，其能够与大肠杆菌二氢叶酸还原酶结构域（EcDHFR）和FKBP12F36V结构域结合，这些结构域因其与大多数哺乳动物蛋白的紧密的结合亲和力和正交性而被广泛使用。然后生成了mCherry融合EcDHFR和来自HIV-1 REV蛋白的NES作为穿梭蛋白，并在HeLa细胞中稳定地整合了mCherry-EcDHFR-NES和FKBP12F36V-GFP-NMNAT1。实验证实在TRAM 1的介导下形成了复合物，而且NMNAT1表现出剂量依赖性地向细胞质的转移，且这种效应在更高浓度下被废除（图1）。 图1:a.通过TRAM的蛋白质转运偶联实现亚细胞核质靶向定位控制示意图。b. TRAM 1的结构。c.用于产生稳定细胞系以研究NMNAT1定位控制的病毒构建体。d. TRAM 1介导形成复合物。e.由TRAM 1驱动的NMNAT1重定位（Credit: Nature） 当同时研究两种蛋白质时，核质转运的量化传统上通过一组代表性图像的共定位度量来完成。而一个开源的计算成像分析流程，能够独立地在细胞核和细胞质中对两种不同蛋白质进行单细胞级别的分析，将是衡量蛋白质运输和比较不同目标蛋白与穿梭蛋白的最准确方法。为此，研究人员建立了这样一个定制的计算成像分析流程，展示了蛋白质稳态定位可以通过分子偶联到含有足够强定位序列并在必要丰度中表达的穿梭蛋白来调节。这种方法适用于不同的细胞类型和密度，将定量分析用于检测剂量、穿梭蛋白和化学计量依赖的再定位，实验结果再次证实NES可以通过小分子介导的偶联主动驱动的NMNAT1再分布。与此同时，研究人员发现，必须存在足够水平的锚或穿梭蛋白才能加强TRAM诱导的靶蛋白的再定位。原则上，只要提供合适的定位强度、表达水平和有效的分子偶联，任何蛋白质的运输都可以重新定位另一个蛋白质。核激素受体如雌激素受体 (ERα) 和糖皮质激素受体 (GR) 表现出从细胞质到细胞核的配体依赖性易位，从而发挥下游转录激活作用。研究人员合成了TRAM 4-7，通过实验证实了这些受体作为核穿梭蛋白的潜力。 为了有效地重新定位靶蛋白，TRAM必须与能够克服靶蛋白内在定位的穿梭蛋白充分结合，蛋白质相对再定位能力的量化将有助于合理选择穿梭-靶组合。为了开发一个定量方法来评估通过TRAM介导的蛋白质重新定位的潜力，研究人员建立了含有一系列遗传构建的多克隆细胞系，这些构建将核激素受体（GR和ERα）与已知的NES序列配对，以及将HIV-1 REV NES与不同的NLS序列配对。随后，研究人员使用不同浓度的相关TRAM处理这些细胞系，然后评估NES标记的蛋白以及核激素受体的重新定位情况。研究结果表明，目标蛋白的重新定位程度依赖于穿梭蛋白（ERα或GR）的特性和目标蛋白的NES序列。此外，研究人员还观察到，不同的NLS构建对HIV-1 REV NES的重新定位能力呈现出梯度变化。通过这些数据，研究人员能够区分不同穿梭蛋白和目标蛋白之间的相对可重新定位性，并为蛋白质对的选择提供了一个定量的评估标准，这对于实现程序化的蛋白质重新定位至关重要。 错位的转录调控蛋白和RNA结合蛋白是多种癌症和神经退行性疾病的特征，将这些蛋白质返回细胞核的靶向方法可能有助于改善疾病驱动表型。本文研究人员利用上述方法，使用核激素受体作为穿梭蛋白，检测了三种已知在疾病中表现出异常定位的突变蛋白——SMARCB1Q318X（一种SMARCB1蛋白的突变型C末端截短，存在于非典型畸胎样和横纹肌样肿瘤，定位与细胞质）、TDP43ΔNLS（缺失了核定位信号的TDP43突变形式，导致它不能正确地定位到细胞核，而是异常地积累在细胞质中，形成病理性的聚集体）和FUSR495X（与ALS相关的FUS蛋白的一种突变形式，通常在细胞质中形成应激颗粒，与疾病的发生发展密切相关）——的重新定位能力。研究结果显示，不同的突变蛋白根据其固有特性，对ERα介导的重新定位的敏感性不同。TDP43ΔNLS和FUSR495X比SMARCB1Q318X更容易被ERα重新定位。此外，研究还发现，FUSR495X在应激颗粒中的定位可以通过TRAM的处理而转移到细胞核，并且这种重新定位与应激颗粒数量的减少相关。这些发现表明，通过靶向蛋白质重新定位的方法，有可能改善疾病相关的蛋白错位现象。 与此同时，研究人员探索了利用TRAM实现内源性蛋白质重新定位的能力。他们采用了CRISPR-Cas9基因编辑技术，将结合域和荧光蛋白标签插入到内源性蛋白PRMT9、SOS1和FKBP12上，使用METAP2和PARP1作为内源性细胞质和核的穿梭蛋白，并合成了能够与它们结合的TRAM 11-13。实验结果证明即使在内源性蛋白表达水平下，通过TRAM介导的内源性蛋白重新定位也是可行的，并且整个细胞群体均显示出均匀的重定位效果，这与外源性表达模型通常只在细胞群体的子集中观察到重定位的现象不同。这表明在内源系统中，可以在整个群体中达到穿梭蛋白与靶蛋白的最低相对比例要求。 最后，研究人员使用TRAM 1处理转导了携带mNMNAT1和EcDHFR标签的腺相关病毒（AAV）的大鼠胚胎的背根神经节（DRG）神经元，发现TRAM 1可以促进NMNAT1从细胞核向轴突的重新定位，NMNAT1在轴突中的表达得到了维持，即使在轴突损伤后也能观察到轴突的健康状况和轴突末端的保护，这表明通过TRAM介导的NMNAT1重新定位确实能够在体外模型中减缓轴突退化的过程。 综上所述，本研究开发了一种定量的单细胞分析方法来检查通过TRAM介导的目标蛋白与穿梭蛋白的耦合潜力，展示了两种蛋白质伙伴的相对表达水平是推动目标蛋白重新定位能力的主要参数，证明通过与内源性穿梭蛋白的耦合可以改变内源性目标蛋白的定位。由此提供了一种新的策略来调控蛋白质的亚细胞定位，为治疗蛋白质定位异常相关疾病提供了新的可能性。通过精确控制蛋白质的定位，不仅可以纠正因蛋白质错位导致的疾病表型，还可以通过蛋白质重新定位赋予有益的功能，更细致地调节细胞功能，从而扩大治疗选择的范围，为开发新的治疗方法提供了理论基础和实验策略。 参考文献 1. Kau, T. R., Way, J. C. & Silver, P. A. Nuclear transport and cancer: from mechanism to intervention. Nat. Rev. Cancer 4, 106–117 (2004). 2. Hung, M.-C. & Link, W. Protein localization in disease and therapy. J. Cell Sci. 124, 3381–3392 (2011). https://doi.org/10.1038/s41586-024-07950-8 责编|探索君 排版|探索君 文章来源|“BioArt” End 往期精选 围观 一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版） 热文 Cell | 是什么决定了细胞的大小？ 热文 Nature | 2024年值得关注的七项技术 热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望 热文 CRISPR技术进化史 | 24年Cell综述

A total of 12 presentations including 6 original posters to showcase MTPA's latest ALS research JERSEY CITY, N.J., Oct. 17, 2024 /PRNewswire/ -- Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced that twelve presentations following expansive research in amyotrophic lateral sclerosis (ALS) will be shared as part of the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) 2024 Annual Meeting, being held virtually October 21-24. "We are excited to present our latest data in ALS research, from preclinical studies to extensive real-world data on RADICAVA® (edaravone) at this year's meeting," said Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs, MTPA. "Our unwavering commitment to ALS research drives us to provide valuable insights to patients, healthcare practitioners and researchers alike, with the ultimate goal of providing treatment options to help improve the lives of those affected by this disease." RADICAVA ORS Results: A presentation will examine the impact of RADICAVA ORS on survival and function in ALS patients, using data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. For this analysis, patients were propensity score-matched with participants from studies MT-1186 A01-A04. Additionally, multiple presentations will explore RADICAVA ORS through multi-center, phase 3b, double-blind, parallel group studies, including a comparison of daily dosing to the U.S. Food and Drug Administration (FDA)-approved on/off regimen, evaluated over 48 weeks (MT-1186-A02) and up to 96 weeks (MT-1186-A04). Safety data from the phase 3 open-label safety extension study (MT-1196-A03) and a post-marketing safety analysis will also be presented. Analysis of Long-term Function and Survival of Radicava ORS® (Oral Edaravone)-Treated Patients With Amyotrophic Lateral Sclerosis vs Propensity Score–Matched PRO-ACT Historical Controls (Stephen Apple, M.D.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Phase 3b Study MT-1186-A02 to Investigate the Superiority of Daily Dosing vs the FDA-approved On/Off Regimen of Oral Edaravone in Patients with ALS (Alejandro Salah, M.D., Ph.D., MBA, MHA; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Phase 3b Study MT-1186-A04 Extension Study to Evaluate the Continued Efficacy and Safety of Radicava ORS® (Oral Edaravone) for up to an Additional 48-Weeks in Patients With Amyotrophic Lateral Sclerosis (Stephen Apple, M.D.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Phase 3, Open-Label, Safety Extension Study of Oral Edaravone Administered Over 96 Weeks in Patients with ALS (MT-1186-A03) (Alejandro Salah, M.D., Ph.D., MBA, MHA; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Summary of the US Safety Data for Radicava ORS®: Findings From the Postmarketing Pharmacovigilance (Stephen Apple, M.D.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Real World Data: Data will be presented from an evaluation of treatment patterns, clinical outcomes and survival rates of RADICAVA-treated individuals living with ALS from the ALS/Motor Neuron Disease (MND) Natural History Consortium (NHC) registry. Additionally, a preliminary analysis will examine the treatment combinations in people with ALS enrolled in the OPTUM claims database. Other presentations include two studies focused on point-of-care quality classifications and at-home telespirometry, evaluating erect and supine slow vital capacity in individuals with ALS, as well as an observational study, Track-ALS, assessing participant compliance and the usability of digital health technologies (DHTs) to remotely monitor ALS progression. Treatment Patterns and Survival Benefit of Edaravone–Treated People With Amyotrophic Lateral Sclerosis in the ALS/MND Natural History Consortium (Stephen Apple, M.D.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Preliminary Analysis of Treatment Combinations in Patients With Amyotrophic Lateral Sclerosis Enrolled in an US-Based Administrative Claims Database (Malgorzata Ciepielewska, M.S.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Smartphone Application-Mediated Supervised At-Home Telespirometry Erect and Supine Slow Vital Capacity (eSVC/sSVC) Measurements in Subjects With Amyotrophic Lateral Sclerosis Identify Statistically Significant Differences in eSVC/sSVC Decline as Function of Non-Invasive Ventilation Treatment Status [NCT05106569] (Eufrosina I. Young, M.D.; SUNY Upstate Medical University) Poster Session: 4:30 p.m. - 6:30 p.m. ET, Tuesday, October 22 Smartphone Application–Mediated, Supervised, At-Home Telespirometry Vital Capacity Measurements in Amyotrophic Lateral Sclerosis: Comparison of American Thoracic Society/European Respiratory Society Point-of-Care Quality Assessment Algorithms Implemented for Slow Vital Capacity and Forced Vital Capacity [NCT05106569] (Eufrosina I. Young, M.D.; SUNY Upstate Medical University) Poster Session: 4:30 p.m. - 6:30 p.m. ET, Tuesday, October 22 Compliance of Home-based Remote Digital Monitoring to Assess ALS progression (Track-ALS) (Katie Terrebonne; Emory University) Poster Session: 4:30 p.m. - 6:30 p.m. ET, Tuesday, October 22 Preclinical Data: Two preclinical studies will be presented, showcasing the effects of edaravone. The first study examines its impact on spinal motor neurons derived from induced pluripotent stem cells (iPSC) taken from a person with ALS carrying the A382T mutation in TDP-43. The second study investigates the role of edaravone on the modulation of glutamate-mediated hyperexcitability in spinal motor neurons using an ALS animal model. Transcriptomic Signature Induced by Edaravone in Motor Neurons From an ALS Patient With a TDP-43 Mutation (Satsuki Mikuriya, M.S.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Edaravone Reduces the Enhanced Glutamatergic Transmission Onto Motor Neurons in the Spinal Cord of a Mouse Model of Amyotrophic Lateral Sclerosis (Alejandro Salah, M.D., Ph.D., MBA, MHA; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 About RADICAVA® (edaravone) and RADICAVA ORS® (edaravone) The U.S. Food and Drug Administration (FDA) approved RADICAVA® (edaravone) on May 5, 2017, and the oral formulation RADICAVA ORS ® (edaravone) on May 12, 2022, for the treatment of amyotrophic lateral sclerosis (ALS). In 2024, the FDA recognized RADICAVA ORS with Orphan Drug Exclusivity based on the major contribution to patient care of the innovative oral formulation. RADICAVA is administered in 28-day cycles by intravenous (IV) infusion. It takes 60 minutes to receive each 60 mg dose. For the initial cycle, the treatment is infused daily for 14 consecutive days, followed by a two-week drug-free period. All cycles thereafter are infused daily for 10 days within a 14-day period, followed by a two-week drug-free period. RADICAVA ORS is taken daily for 14 consecutive days followed by a 14-day drug-free period for the initial treatment cycle. For subsequent treatment cycles, RADICAVA ORS is taken for 10 days within a 14-day period followed by a 14-day drug-free period. RADICAVA ORS should be taken in the morning after overnight fasting. Patients should not eat or drink (except water) within one hour after taking RADICAVA ORS.1 Edaravone was discovered and developed for ALS by Mitsubishi Tanabe Pharma Corporation (MTPC) and commercialized in the U.S. by Mitsubishi Tanabe Pharma America, Inc. (MTPA). The MTPC group companies began researching ALS in 2001 through an iterative clinical platform over a 13-year period. In 2015, edaravone was approved as RADICUT® for the treatment of ALS in Japan and South Korea. Marketing authorizations were subsequently granted in Canada (October 2018), Switzerland (January 2019), Indonesia (July 2020), Thailand (April 2021), Malaysia (December 2021) and Brazil (February 2024). Marketing authorization for RADICAVA® Oral Suspension was granted in Canada (November 2022) and Switzerland (May 2023), and RADICUT® Oral Suspension 2.1% was granted regulatory approval in Japan in December 2022. To date, in the U.S., RADICAVA and RADICAVA ORS have been used to treat over 16,000 people with ALS, with over 2.0-million days of therapy, and have been prescribed by over 2,400 HCPs.2-4 IMPORTANT SAFETY INFORMATION Hypersensitivity Reactions RADICAVA (edaravone) and RADICAVA ORS (edaravone) are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients of this product. Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have occurred with RADICAVA. Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue RADICAVA or RADICAVA ORS, treat per standard of care, and monitor until the condition resolves. Sulfite Allergic Reactions RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown but occurs more frequently in asthmatic people. Adverse Reactions The most common adverse reactions (≥10%) reported in RADICAVA-treated patients were contusion (15%), gait disturbance (13%), and headache (10%). In an open label study, fatigue was also observed in 7.6% of patients receiving RADICAVA ORS. Pregnancy Based on animal data, RADICAVA and RADICAVA ORS may cause fetal harm. To report suspected adverse reactions or product complaints, contact Mitsubishi Tanabe Pharma America, Inc., at 1-888-292-0058. You may also report suspected adverse reactions to the FDA at 1-800-FDA-1088 or . INDICATION RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). For more information, including full Prescribing Information, please visit . About Mitsubishi Tanabe Pharma America, Inc. Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC). It was established by MTPC to develop and advance our pipeline as well as commercialize approved pharmaceutical products in North America. For more information, please visit or follow us on X (formerly Twitter), Facebook and LinkedIn. About Mitsubishi Tanabe Pharma Corporation Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of Mitsubishi Chemical Group (MCG), is one of the oldest pharmaceutical companies in the world, founded in 1678. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. MCG has positioned health care as its strategic focus in its management policy, "Forging the future". MTPC sets the MISSION of "Creating hope for all facing illness". To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on "precision medicine" to provide drugs with high treatment satisfaction and additionally working to develop "around the pill solutions" to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to . Media inquiries: [email protected] 1 RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2022. 2 Data on file. Mitsubishi Tanabe Pharma America, Inc. 3 Data on file. Mitsubishi Tanabe Pharma America, Inc. 4 Data on file. Mitsubishi Tanabe Pharma America, Inc. SOURCE Mitsubishi Tanabe Pharma America WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Results Presented in an Oral Presentation at the Society for Neuroscience Annual Meeting RNS60 Protected Motor Neurons and Neuromuscular Junctions and Reduced Neuroinflammation TACOMA, Wash., Oct. 9, 2024 /PRNewswire/ -- Revalesio, a clinical-stage pharmaceutical company developing treatments for acute and chronic neurological disorders, today announced new data showing that Revalesio's investigational therapeutic, RNS60, protected motor neurons in the prpTDP-43A315T-UeGFP mouse model of ALS. PrpTDP-43A315T-UeGFP mice express a mutation of the human TDP43 gene and develop progressive motor neuron degeneration, leading to gait abnormalities, muscle weakness, and eventually death, mimicking key features of ALS. TDP43-associated pathology is found in approximately 97% of people with ALS. The results were presented today during the Nanosymposium ALS Therapeutics at the Society for Neuroscience Annual Meeting. "There is a great need for treatment options to slow the progression of ALS," said Hande Ozdinler, Ph.D., Associate Professor of Neurology at Northwestern University Feinberg School of Medicine and Principal Investigator of the study. "These promising preclinical findings warrant further investigation of the potential role of RNS60 in protecting motor neurons and preserving mitochondrial function, key factors in the pathogenesis of ALS." "These exciting results suggest that RNS60 has potential to mitigate neurodegeneration due to TDP-43 pathology," said Mukesh Gautam, PhD, Research Assistant Professor of Neurology at Northwestern University Feinberg School of Medicine and presenting author at the Society for Neuroscience Annual Meeting. "Since TDP-43 pathology contributes to a large population of both familial and sporadic ALS patients, these results are particularly promising." In this study, 30-day old prpTDP-43A315T-UeGFP mice showing signs of degeneration were treated with RNS60 every other day for 60 days. Immunohistochemistry was performed to quantitatively assess activated microglia (immune cells that patrol the central nervous system [CNS] for pathogens and damage) and activated astrocytes (cells in the CNS that perform metabolic, structural, homeostatic, and neuroprotective tasks). Ultrastructural integrity of neuronal mitochondria was studied via electron microscopy. RNS60 treatment significantly a) improved mitochondrial ultrastructure in the motor neurons, b) reduced the extent of astrogliosis and microgliosis in mice and c) protected health and stability of upper motor neurons and neuromuscular junctions compared to placebo-treated mice. "These results add to the growing body of preclinical and clinical evidence that RNS60 may provide neuroprotective effects in ALS," said Bert van den Bergh, Revalesio's Executive Chairman on the Board of Directors, and former President of Neuroscience Products at Eli Lilly and Company. "We are simultaneously advancing RNS60 in planned clinical trials for the treatment of patients with ALS and ischemic stroke with the goal of improving the lives of people with these devastating conditions." About RNS60 RNS60 is an investigational therapeutic being developed to provide disease modifying and potentially restorative treatments for neurological diseases. In preclinical studies, RNS60 activated intracellular signaling pathways to increase mitochondrial biogenesis and function and reduce inflammation. RNS60 safely protected neurons and oligodendrocytes and modulated the activity of immune cells to restore homeostasis. RNS60 has been granted Orphan Drug and Fast Track designations for ALS from the U.S. Food and Drug Administration. About Revalesio Revalesio is a clinical-stage pharmaceutical company with a vision to change the future of treatment for acute and chronic neurological disorders. The company's lead clinical program for RNS60 is ischemic stroke with additional programs in ALS and other neurological disorders. The company's pioneering technology, founded in physics, addresses fundamental mechanisms involved with proper cellular function to slow disease progression and improve quality of life. For more information, please visit revalesio.com and engage with us on LinkedIn. Media Lori Murray [email protected] SOURCE Revalesio Corporation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED