Teriparatide(Eli Lilly)

2岁的小乐（化名）原本活泼好动，最近却变得总是跌跌撞撞，不愿走路。家人以为是缺钙，就一顿猛补钙片和维生素D。可奇怪的是，小乐不仅没好转，反而开始走路“像踩棉花”，甚至出现了X型腿。更让人心惊的是，才两岁的小乐，门牙居然松动脱落了！这可把妈妈吓坏了，赶紧带孩子跑了好几家医院。血钙正常、维生素D也不低，但X光一拍，医生愣住了——小乐的骨头密度异常低，骨骼发育严重滞后。进一步检查发现，小乐碱性磷酸酶（ALP）水平远低于正常儿童的参考值，结合乳牙早脱、骨骼变形、运动发育迟缓，最终确诊为：低磷酸酶症（Hypophosphatasia，HPP）——一种因组织非特异性碱性磷酸酶（TNSALP）基因突变引起的罕见骨矿化遗传病。1什么是磷酸酯酶症磷酸酯酶症（hypophosphatasia，HPP）是一种罕见的遗传性代谢疾病，该病的病因是编码非特异性碱性磷酸酶(TNSALP)的ALPL基因的功能缺失变异引起组织TNSALP活性低下或消失为特征。目前已经报道了超过400个ALPL基因突变。2临床表现低磷酸酶症（HPP）是一种由于碱性磷酸酶活性显著降低所导致的遗传性代谢性骨病，其临床表现高度异质，严重程度差异很大。轻者可能仅表现为乳牙早期脱落，重者则可出现严重的骨质异常、反复骨折、肌肉无力，甚至因呼吸衰竭致死。起病年龄对症状表现有显著影响，越早起病往往代表疾病越严重，尤其是围产期和婴儿型HPP预后最差。骨骼系统异常是HPP最核心的临床特征。乳牙无明显外力下早脱，尤其是下前牙，是患儿最常见和最早期的表现之一。其他骨骼症状包括骨质疏松、身材矮小、骨骼畸形、反复骨折及步态异常等，这些症状多源于骨矿化障碍。成人型患者可因持续性骨痛、肌无力和运动能力下降而影响生活质量。由于骨骼肌附着点的异常，也常见肌无力表现。HPP还可能累及多个系统，导致神经系统、呼吸系统等症状。神经系统方面，部分婴儿可能因维生素B6代谢障碍引发惊厥和抽搐。重症患儿因胸廓畸形、肺发育不足可出现呼吸困难，严重时甚至致命。此外，部分患者报告有慢性疲劳、关节松弛和广泛性疼痛等症状，进一步加重对生活的影响。3诊断低磷酸酶症的诊断应基于典型临床表现与实验室检查的综合评估。对于婴幼儿或成人期起病，表现为乳牙早脱、骨软化或佝偻病样改变，同时血清碱性磷酸酶（ALP）活性呈特异性降低的患者，应高度怀疑HPP的可能。患者常伴有癫痫发作、骨骼疼痛、骨骼畸形、反复骨折、肌肉乏力、步态异常及身材矮小等表现，具有一定的临床特征性。生化检查是诊断的核心。最重要的指标是血清ALP活性显著低于同龄正常参考范围，具有高度特异性。其他常见生化特征包括正常或升高的血钙、磷、25-羟维生素D（25OHD）水平，部分重症患者可合并高钙血症或高尿钙。尿液磷代谢产物（如磷酸乙醇胺、吡哆醛-5-磷酸等）水平升高也可提供支持性信息。影像学检查对于确认骨骼病变及评估其严重程度至关重要。X线平片可显示出佝偻病或骨软化样改变，包括颅骨钙化异常、长骨干骺端模糊或毛糙、四肢弯曲变形、脊柱侧弯、假骨折线等特征性征象。牙齿脱落与牙根发育异常也可见于影像。若条件允许，进行ALPL基因突变分析是确诊的金标准。发现功能性突变（尤其是失活性突变）将进一步明确诊断，同时对遗传咨询和家系筛查也具有指导意义。4治疗低磷酸酶症（HPP）的治疗近年来取得显著进展，酶替代疗法（ERT）已成为核心方法。Asfotase alfa（Strensiq）是首个获批用于HPP的靶向药物，通过补充缺陷的碱性磷酸酶，促进骨矿化，改善骨骼异常，显著降低婴幼儿型HPP的死亡率。目前该药尚未在中国全面上市，仅可在博鳌乐城先行区使用。成人型HPP尚无标准疗法，但特立帕肽可刺激ALP合成，改善骨折愈合；BPS804能提高ALP活性、促进骨形成并减少骨吸收，具有潜在治疗价值。基因治疗方面已有动物实验尝试，但因安全性问题尚未应用于临床。总体来看，HPP治疗正从支持性治疗迈向病因靶向干预，未来有望拓展更多有效手段。参考文献：[1]许莉军, 姜艳, 夏维波. 低磷酸酯酶症的研究进展，国际内分泌代谢杂志，2015,35 (3):211-214.[2]赵真, 夏维波, 邢小平, 等. 婴儿型低磷酸酯酶症组织非特异性碱性磷酸酶基因突变检测. 中华内科杂志,2013,52(10):824-828.[3]Whyte MP,Greenberg CR,Salman NJ, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med, 2012,366(10):904-913.来源 | 梅斯医学编辑 | wanny神经系统罕见病交流群↓点击下方“阅读原文”，下载梅斯医学APP吧！

SAN DIEGO, May 15, 2025 /PRNewswire/ -- Abzena, the leading end-to-end integrated CDMO + CRO for complex biologics and bioconjugates, has announced today the formation of its Scientific Advisory Board (SAB) comprised of biopharma industry experts with diversified expertise in Discovery Research & Development (R&D) and Chemistry, Manufacturing, and Controls (CMC). The new advisory board will work closely with Abzena's scientific and commercial leadership to provide strategic guidance and expert insights that support Abzena's continued commitment to growth and innovation. Matt Stober, CEO of Abzena, said, "The establishment of the Scientific Advisory Board was a strategic decision to help guide the future of Abzena. We have seen considerable momentum over the past few years in supporting complex and innovative modalities, such as Antibody-drug conjugates (ADCs), Antibody-oligonucleotide conjugates (AOCs), and bispecifics. We aim to continue building upon this by offering the most state-of-the-art technologies and capabilities to support our customers' programs. These experts will be instrumental in assisting us with this mission by evaluating our strategies and providing recommendations that will further enhance our ability to move medicines forward to patients faster." Joe Principe, CCO of Abzena, said, "We are honored to welcome these distinguished individuals to our Scientific Advisory Board. These founding members are recognized leaders in our industry, bringing a wealth of expertise that will help guide us as we continue through this significant phase of our growth. We look forward to their contributions and the positive impact that they will have on our organization." Founding members of Abzena's Scientific Advisory Board are: John Knight, Ph.D., is the founder of JKONSULT, a UK-based consulting firm, where he provides process chemistry and CMC consulting services for early-stage chemical development and transfer-to-plant projects, with a primary focus on material supplies for toxicological studies, Phase I, and Phase II clinical trials. Dr Knight has 38 years of pharmaceutical industry experience, with prior roles at GSK, Vernalis, and Evotec. Kamal Egodage, Ph.D., MBA, is the President of Lasanth® Consulting, where he provides consultation services for biologics that span from discovery through commercialization, including CMC development, regulatory strategy, interactions with health authorities, and corporate development strategy. Prior to establishing his consultancy in 2017, Dr. Egodage accumulated over 20 years of industry experience at Eli Lilly, Pharmacia, Monsanto, Symic Bio, and Novartis (Switzerland), where he was the Head of Strategy and Business Development for Biologics. Morris Rosenberg, D.Sc., is an independent consultant with over 25 years of experience in the development of therapeutic agents to treat a variety of human diseases. As a consultant, he provides advisory services to early research and clinical-stage companies on product development strategies for biologics, biosimilars, and ADC therapies. Prior to this, Dr Rosenberg played a key role in the development and commercialization of ADC-based therapies at Seattle Genetics and Immunomedics and participated in the development and launch of Trodelvy®, Adcetris®, Avonex®, Angiomax®, Xigris®, and Forteo®. Scott Rudge, Ph.D., co-founded RMC Pharmaceutical Solutions in 2004, which was acquired by Syner-G BioPharma Group in January 2023. He is a Principal Consultant with Syner-G, and leads its Commercial and Scientific Advisory Boards, and is a member of the Syner-G Board. He also currently serves as SVP of Product Development at Margaux Biologics, Head of CMC for Antidote Therapeutics and Optigo Biotherapeutics, is a Key Advisor to Jurata, and is an Adjunct Professor of Chemical Engineering at the University of Colorado. Dr Rudge has over 33 years of experience directing Process Engineering, Process Development, Product Development, and overall Pharmaceutical Operations, and has built and led several organizations in the biopharmaceutical industry. Steven Sandoval is the founder and serves as the CEO/ Operations Head of Pharmaceutical Technical Solutions, Inc. (PTSI). Providing technical oversight and client representative support to the Biotechnology, Gene Therapy, Viral Vector, Cell Therapy, T-CELL, CAR T, mRNA, 503a/ 503b Compounding, and Vaccine Pharmaceutical Industries since 2010. Prior to this, he held senior leadership roles at Pfenex Inc., Parsons (BMS), and Amgen. He has over 30 years of experience in biopharmaceutical manufacturing, operations, CMC tech transfer, engineering, facilities, and quality leadership services. Tatyana Touzova is the Chief Pharmaceutical Development & Manufacturing Officer at SERA Medicines, where she oversees CMC, regulatory, and nonclinical development from drug discovery through clinical stages. Prior to this, she held the position of Chief Operating Officer at AstralBio, AlmataBio, and ValenzaBio, where she directed CMC, manufacturing, and regulatory operations for multiple clinical-stage programs. She has over 35 years of experience in drug development, regulatory affairs, and commercial manufacturing of biologics and complex therapeutics and is recognized as an expert in CMC strategy, GMP compliance, and global regulatory submissions. About Abzena Abzena is the leading end-to-end bioconjugate and complex biologics CDMO + CRO. From discovery through commercial launch, we support customers with fully integrated programs or individual services designed to de-risk and streamline the development of new treatments for patients in need. With the ability to tailor its strategy and customer experience to each project, Abzena develops and implements innovative solutions that enable biotech and biopharma companies to realize the full potential of their molecule and move medicines forward faster. The company has research, development, and cGMP facilities across locations in San Diego, CA, Bristol, PA, and Cambridge, UK. Abzena is owned by Welsh, Carson, Anderson & Stowe, one of the world's leading private equity investors. Learn more at abzena.com. SOURCE Abzena WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED