INTRODUCTIONChronic subdural hematoma (cSDH), a condition that develops over time, is characterized by inflammation, angiogenesis, and membrane development. As the population's average age increases, the incidence of cSDH is expected to grow. While surgery is the primary treatment technique, medicinal therapy options are being explored for high-risk patients. Currently, the most effective therapy combination is dexamethasone (Dex) and atorvastatin (Ato); however, it is associated with an increased risk of mortality. This study explored the effects of bevacizumab (Bev), a vascular endothelial growth factor antagonist, on cSDH.MATERIALS AND METHODSNinety-five rats were divided into four groups (n = 18): sham, control hematoma, Dex-Ato, and Bev. Two separate autologous blood injections into the subdural space were used as the model. Weight was monitored for all rats to assess changes in their overall health. The control group was given i.p. saline, the Dex-Ato treatment was given by gavage, and the Bev treatment was given i.p. On seventh, 14th and 21st days six rats from each group were sacrificed and analyzed, while 23 rats were excluded from the experiment.RESULTSThe maximum immunological response to cSDH was observed on day 14. Hematoma volume decreased over time in all groups. Dex-Ato and Bev were both found effective, while Dex-Ato caused weight loss.CONCLUSIONBev had similar effects to the Dex-Ato group and was well tolerated by rats. Given that cSDH is a disease of the elderly and vulnerable populations, Bev may be a viable alternative that can shed light on the disease's etiology for future research.

2024-06-01·Clinical Lymphoma Myeloma and Leukemia

Outcome of Patients With Relapsed Acute Promyelocytic Leukemia

Article

作者: Kantarjian, Hagop ; Borthakur, Gautam ; Short, Nicholas ; Patel, Keyur P ; DiNardo, Courtney D ; Jabbour, Elias ; Kadia, Tapan ; Yilmaz, Musa ; Ravandi, Farhad ; Loghavi, Sanam ; Sasaki, Koji ; Pierce, Sherry

BACKGROUNDThe outcome of patients with acute promyelocytic leukemia (APL) has improved significantly since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as APL therapies. The optimal therapy for APL relapse is believed to require autologous or allogeneic stem cell transplantation (SCT) based on historical experience.STUDY AIMSTo evaluate the outcome of patients with relapsed APL before and after the era of ATRA-ATO.PATIENTS AND METHODSWe reviewed 61 patients with relapsed APL treated from November 1991 to June 2023; 31 patients (51%) received modern therapy with the combination of ATRA and ATO with and without idarubicin and gemtuzumab ozogamicin (GO).RESULTSOverall, 56 patients (92%) achieved CR after the first salvage therapy; 20 patients received SCT (10 autologous SCT;10 allogeneic SCT). With a median follow-up time of 138 months, the median survival durations were 32 months and 164 months with historical therapy vs. modern (ATRA-ATO) therapy (P = .035); the 5-year survival rates were 44% vs. 71%. With a 10-month landmark analysis, the median survival durations were 102 months vs. not reached, and the 5-year survival rates were 57% and 70% without SCT vs. with SCT (P = .193). The survival benefit with SCT was more prominent in the historical therapy era. However, patients who received the modern combination therapy of ATRA-ATO with and without idarubicin and GO had similar outcomes without vs. with SCT (P = .848).CONCLUSIONThe combination of ATRA-ATO (+/- GO and idarubicin) is a highly effective salvage therapy in relapsed APL. The use of SCT may not be needed after first relapse-second remission but may be considered in subsequent relapses.

Pharmaceutics

Co-Delivery of Dragon’s Blood and Alkanna tinctoria Extracts Using Electrospun Nanofibers: In Vitro and In Vivo Wound Healing Evaluation in Diabetic Rat Model

Article

作者: AlMotawa, Rana Y ; Tawfik, Essam A ; Al-Taweel, Areej ; Alhamid, Ghadeer ; Alfassam, Haya A ; Ghaffar, Safina ; Alzahrani, Dunia A ; Almomen, Aliyah ; Badran, Mohamed M ; Alomrani, Abdullah H ; Fathaddin, Amany ; Orfali, Raha

The increasing prevalence of diabetic wounds presents a significant challenge due to the difficulty of natural healing and various obstacles. Dragon’s blood (DB) and Alkanna tinctoria (AT) are well recognized for their potent healing abilities, which include potent antibacterial and anti-inflammatory activities. In this study, electrospun nanofibers (NFs) based on polyvinyl pyrrolidone (PVP) were co-loaded with both DB and AT, aiming to magnify their efficacy as wound-dressing applications for diabetic wound healing. The evaluation of these NFs as wound dressings was conducted using a streptozotocin-induced diabetic rat model. Electrospun NFs were prepared using the electrospinning of the PVP polymer, resulting in nanofibers with consistent, smooth surfaces. The loading capacity (LC) of AT and DB into NFs was 64.1 and 70.4 µg/mg, respectively, while in the co-loaded NFs, LC was 49.6 for AT and 57.2 µg/mg for DB. In addition, X-ray diffraction (XRD) revealed that DB and AT were amorphously dispersed within the NFs. The loaded NFs showed a dissolution time of 30 s in PBS (pH 7.4), which facilitated the release of AT and DB (25–38% after 10 min), followed by a complete release achieved after 180 min. The antibacterial evaluation demonstrated that the DB-AT mixture had potent activity against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). Along with that, the DB-AT NFs showed effective growth inhibition for both P. aeruginosa and S. aureus compared to the control NFs. Moreover, wound healing was evaluated in vivo in diabetic Wistar rats over 14 days. The results revealed that the DB-AT NFs improved wound healing within 14 days significantly compared to the other groups. These results highlight the potential application of the developed DB-AT NFs in wound healing management, particularly in diabetic wounds.

项与 DB ATO 相关的新闻（医药）

2021-02-21

·GlobeNewswire

Decibel Therapeutics to Present at the 44th Annual Association for Research in Otolaryngology (ARO) Conference

BOSTON, Feb. 19, 2021 (GLOBE NEWSWIRE) -- Decibel Therapeutics (Nasdaq: DBTX), a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, announced today that it will present findings from its drug discovery and development programs at the 44th Annual MidWinter Meeting of the Association for Research in Otolaryngology (ARO), which will be held virtually February 20–24, 2021. The Decibel team will have a total of eight podium and poster presentations during this year’s meeting. Several presentations will focus on DB-OTO, Decibel’s investigational gene therapy being developed to restore hearing in children with a deficiency in the otoferlin gene, and DB-ATO, a regenerative gene therapy program designed to restore balance in patients with bilateral vestibulopathy, or BVP, by regenerating lost hair cells within the vestibule. Podium Presentations Podium 18.3 | Promoter Control Optimizes AAV-ATOH1 Gene Therapy for Vestibular Hair Cell Regeneration Presenter: Tian Yang, Ph.D. Session Title: Regeneration of Hair Cells & Synapses Date & Time: Monday, February 22, 3:30–3:45 p.m. ET Podium 25.2 | Development of an AAV-Based Gene Therapy for Children with Congenital Hearing Loss Due to Otoferlin Deficiency (DB-OTO) Presenter: Adam Palermo, Ph.D. Session Title: Inner Ear Therapeutics Date & Time: Tuesday, February 23, 3:15–3:30 p.m. ET Podium 25.3 | Mechanisms of Promoter-Driven AAV Toxicity in the Ear Presenter: Gabriela Pregernig, Ph.D. Session Title: Inner Ear Therapeutics Date & Time: Tuesday, February 23, 3:30–3:45 p.m. ET Podium 25.4 | Safely Delivering Adeno-Associated Viral Vectors to the Ear for Therapeutics Presenter: Peter Weber, MBA, M.D. Session Title: Inner Ear Therapeutics Date & Time: Tuesday, February 23, 3:45–4:00 p.m. ET Poster Presentations SU97 | Leveraging single cell genomics with tissue culture to identify and screen targets for vestibular regeneration M117 | Gentamicin-Induced Models of Vestibular Dysfunction in Mice for Evaluating Therapeutic Potential of Vestibular Hair Cell Regeneration T96 | Transcriptional comparison of AAV-Atoh1 and AAV-Atoh1/Pou4f3/Gfi1 regenerated hair cells in the neonatal mouse cochlea W78 | Inner Ear Tropism of Natural and Engineered AAV Serotypes in Non-Human Primate Enables Therapeutic Targeting of a Diverse Set of Cochlear Cell Types About Decibel Therapeutics Decibel Therapeutics is a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, one of the largest areas of unmet need in medicine. Decibel has built a proprietary platform that integrates single-cell genomics and bioinformatic analyses, precision gene therapy technologies and expertise in inner ear biology. Decibel is leveraging its platform to advance gene therapies designed to selectively replace genes for the treatment of congenital, monogenic hearing loss and to regenerate inner ear hair cells for the treatment of acquired hearing and balance disorders. Decibel’s pipeline, including its lead gene therapy program, DB-OTO, to treat congenital, monogenic hearing loss, is designed to deliver on our vision of a world in which the privileges of hearing and balance are available to all. Investor Contact: Julie Seidel Stern Investor Relations, Inc. julie.seidel@sternir.com 212-362-1200 Media Contact: Matthew Corcoran Ten Bridge Communications mcorcoran@tenbridgecommunications.com 617-866-7350

基因疗法

2021-01-27

·医药合作投融资联盟

Decibel提交纳斯达克IPO，拟募资7500万美元开发基因疗法恢复听力

2021年1月24日，根据纳斯达克报道，Decibel Therapeutics已向美国证券交易委员会提交申请，希望通过首次公开募股筹集至多7500万美元。 2015年10月15日，Third Rock以5200万美元A轮融资创立该公司，2017年7月获得了GV等的投资，2018年完成C轮融资5500万美元，2020年11月完成8200万美元D轮融资。 2020年11月8日，Decibel与佛罗里达大学（UF）和加利福尼亚大学旧金山分校（UCSF）达成独家许可协议以用于腺相关病毒（AAV）基因治疗技术设计基因治疗产品，旨在恢复因otoferlin基因突变而导致严重先天性听力丧失的个体的听力。其与Regeneron合作的领先的基因治疗产品候选产品DB-OTO正在开发中，旨在为因otoferlin基因突变而患有严重听力损失的人提供恢复听力。 Decibel的平台整合了单细胞基因组学和生物信息学分析，使用精准的基因治疗技术来推进一系列临床前基因治疗项目，这些项目旨在有选择地替换基因以治疗先天性，单基因性听力损失。该公司还推进了旨在恢复双侧前庭病患者平衡的基因治疗项目 DB-ATO和用于预防顺铂引起的听力损失的DB-020，目前正在Ib期试验中进行评估。 2020年11月9日，波士顿，临床阶段生物技术公司Decibel Therapeutics正在开发新型修复性基因疗法，以治疗听力损失和平衡障碍，宣布完成超额认购的D轮融资，筹集了8220万美元。 D轮融资由OrbiMed牵头，BlackRock Health Sciences，Casdin Capital，Janus Henderson，Samsara BioCapital和Surveyor Capital进行了新的投资。现有的投资者也参与了此次融资，包括Foresite Capital，GV，S-Cubed Capital，Sobrato Capital，SR One，Third Rock Ventures和其他机构投资者。在筹集资金的同时，该公司已任命OrbiMed的合伙人Peter A. Thompson为其董事会成员。所得款项将部分用于支持推进Decibel治疗项目所需的临床和临床前研究。DB-OTO是Decibel的研究性基因疗法，用于恢复因otoferlin基因缺陷而导致的先天性耳聋儿童的听力，目前正在进行临床前研究，Decibel预计将于2022年开始临床试验。该项目是与Regeneron Pharmaceuticals合作开发的，使用专有的细胞选择性启动子来精准控制耳蜗毛细胞中的基因表达。DB-020是Decibel预防与顺铂为基础的化学疗法相关的耳毒性的研究药物，目前正在癌症患者的1B期研究中，预计在2021年将获得人体最初的疗效数据。 Decibel首席执行官Laurence Reid博士 “听力和平衡障碍历来被生物制药行业所忽视，即使它们对全球数亿人的生命造成了毁灭性的破坏。在Decibel，我们致力于通过精准疗法来恢复听力和平衡，旨在专门为耳朵的正确细胞提供正确的遗传药物。” Decibel首席执行官Laurence Reid博士说。“我们感谢这组杰出的投资者选择与我们合作以推进这一愿景。” OrbiMed的合伙人Peter Thompson表示：“我们相信Decibel已经组建了一支出色的团队，并且正在开发一系列重要的新药来治疗内耳疾病。” “ OrbiMed非常高兴能为Decibel提供支持，因为他们将继续前进并在这一重要的新兴领域中建立领先的公司。” 关于Decibel Therapeutics Decibel Therapeutics是一家临床阶段的生物技术公司，致力于开发可恢复内耳功能性毛细胞以治疗听力和平衡障碍的疗法。借助行业领先的单细胞基因组学功能和专有的基因治疗技术，Decibel建立了世界上第一个旨在恢复听力和平衡功能的综合研究，发现和药物开发平台。Decibel的产品线，包括用于治疗先天性单基因性耳聋的先导基因治疗项目（DB-OTO）和耳毒性预防项目，旨在实现我们对所有人享有听力和平衡特权的世界的愿景。 ‍ 版权声明：本文转自医药合作投融资联盟，如不希望被转载的媒体或个人可与我们联系，我们将立即删除【关于药融圈】药融圈围绕我国生物医药产业链，针对生物医药大数据、技术和资本投资、药融园(产业园)等开展系列系统性工作，促进我国生物医药产业健康发展，完善产业链，共同面对全球合作和竞争。点分享点点赞点在看