新型 ALS 疗法进入全球项目的人体试验阶段

TRCN-1023 is designed to restore nerve-muscle communication

TRCN-1023 旨在恢复神经与肌肉之间的通信

Trace Neuroscience has launched its clinical development program for TRCN-1023, an experimental treatment for amyotrophic lateral sclerosis (ALS) that is designed to restore the function of UNC13A, a protein involved in nerve-muscle communication.

Trace Neuroscience 已启动 TRCN-1023 的临床开发项目。TRCN-1023 是一种用于治疗肌萎缩侧索硬化症（ALS）的实验性疗法，旨在恢复 UNC13A 的功能；UNC13A 是一种参与神经与肌肉通信的蛋白质。

The global clinical program includes FUNCTION ALS , a company-sponsored Phase 1/2 clinical trial authorized in the U.K. and the Netherlands and expected to enroll participants at sites in the U.S., Canada, Germany, the Netherlands, and the U.K. as they open. Another trial in the program is LAUNCH ALS, an investigator-led clinical study underway in China in partnership with Tenacia Biopharmaceutical , where the first patients have already been dosed.

这项全球临床项目包括 FUNCTION ALS，这是一项由公司赞助的 Phase 1/2 临床试验，已获英国和荷兰批准；随着各试验中心陆续启用，预计将在美国、加拿大、德国、荷兰和英国招募参与者。该项目的另一项试验是 LAUNCH ALS，这是一项由研究者发起、与 Tenacia Biopharmaceutical 合作在中国开展的临床研究，首批患者已接受给药。

“Our team helped establish UNC13A as one of the most compelling genetically validated targets in ALS,” Eric Green, MD, PhD, Trace’s co-founder and CEO, said in a company press release . “We are thrilled to now be advancing TRCN-1023 into the clinic with a global early development strategy that is poised to generate a robust clinical data package with the urgency that ALS demands.”

Trace 联合创始人兼首席执行官 Eric Green（MD、PhD）在公司新闻稿中表示：“我们的团队帮助确立了 UNC13A 作为 ALS 领域最具吸引力、且经过遗传学验证的靶点之一的地位。我们非常振奋，如今正通过一项全球早期开发策略推动 TRCN-1023 进入临床阶段；该策略有望以 ALS 所要求的紧迫速度，形成一套扎实的临床数据。”

ALS occurs when motor neurons — the nerve cells responsible for muscle movement — become damaged and die over time. As the disease progresses, muscle weakness causes patients to lose the ability to walk, speak, swallow, and eventually breathe. Current treatments are limited, creating a need for new therapeutic options.

当负责肌肉运动的神经细胞——运动神经元——受损并随时间推移逐渐死亡时，就会发生 ALS。随着疾病进展，肌无力会导致患者失去行走、说话和吞咽的能力，并最终无法呼吸。目前的治疗选择有限，因此亟需新的治疗方案。

TRCN-1023 is an antisense oligonucleotide, a short piece of genetic material, designed to bind to messenger RNA, the “instruction copy” cells use to produce proteins from DNA. By binding to UNC13A messenger RNA, TRCN-1023 is designed to help regulate how that RNA is processed, guiding the formation of functional UNC13A protein.

TRCN-1023 是一种反义寡核苷酸，即一小段遗传物质，旨在与信使 RNA 结合；信使 RNA 是细胞依据 DNA 生成蛋白质时使用的“指令副本”。通过与 UNC13A 信使 RNA 结合，TRCN-1023 旨在帮助调节该 RNA 的加工方式，引导形成功能正常的 UNC13A 蛋白。

The target of TRCN-1023 is UNC13A, whose protein function is disrupted in most people with ALS. This occurs when TDP-43, a protein normally found in the nucleus, forms abnormal clumps outside that cellular compartment and disrupts the normal processing of UNC13A messenger RNA. As a result, faulty segments can remain in the RNA, making it unstable.

TRCN-1023 的靶点是 UNC13A，而大多数 ALS 患者的 UNC13A 蛋白功能均受到破坏。当通常存在于细胞核内的蛋白质 TDP-43 在该细胞区室之外形成异常团块，并扰乱 UNC13A 信使 RNA 的正常加工时，就会出现这种情况。因此，错误片段可能残留在 RNA 中，使其变得不稳定。

By binding to UNC13A messenger RNA, TRCN-1023 is designed to help restore proper RNA processing and guide the formation of functional UNC13A protein. This may help improve signaling between nerves and muscles.

通过与 UNC13A 信使 RNA 结合，TRCN-1023 旨在帮助恢复正确的 RNA 加工，并引导形成功能正常的 UNC13A 蛋白。这可能有助于改善神经与肌肉之间的信号传递。

“UNC13A is among the most promising targets in ALS research today with a strong grounding in human genetics and mechanistic biology,” said Dame Pamela Shaw, MD, a professor of neurology at the University of Sheffield in England and FUNCTION ALS chief investigator. “There is compelling rationale for restoring this protein’s function, which has relevance to the vast majority of ALS patients.”

英国谢菲尔德大学神经病学教授、FUNCTION ALS 首席研究者 Pamela Shaw 女爵（MD）表示：“UNC13A 是当今 ALS 研究中最具前景的靶点之一，拥有坚实的人类遗传学和机制生物学基础。恢复这种蛋白质的功能具有令人信服的科学依据，并且与绝大多数 ALS 患者相关。”

Designed with input from people living with ALS and their caregivers and with help from artificial intelligence tools , the FUNCTION ALS clinical trial will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of TRCN-1023 compared with a placebo in about 30 people with ALS whose symptoms started up to two years prior to enrollment.

FUNCTION ALS 临床试验的设计吸纳了 ALS 患者及其照护者的意见，并借助了人工智能工具。该试验将在约 30 名症状于入组前不超过两年开始出现的 ALS 患者中，评估 TRCN-1023 与安慰剂相比的安全性、耐受性、药代动力学和药效动力学活性。

Before being randomly assigned to receive TRCN-1023 or a placebo, patients will enter a two-week run-in period during which they will be asked to wear digital sensors on their dominant wrist and ankle to collect information about daily movement. They will also complete speech assessments at home.

在被随机分配接受 TRCN-1023 或安慰剂之前，患者将进入为期两周的导入期；在此期间，他们将被要求在惯用侧手腕和脚踝佩戴数字传感器，以收集日常活动信息。他们还将在家中完成言语评估。

TRCN-1023 and the placebo will be delivered into the spinal canal through intrathecal injection. Researchers will record side effects, how TRCN-1023 moves into, through, and out of the body, known as pharmacokinetics, and its biological effects in the body, known as pharmacodynamics. They will also track changes in movement, speech, functional abilities, and biomarkers.

TRCN-1023 和安慰剂将通过鞘内注射给药至椎管内。研究人员将记录副作用、TRCN-1023 进入人体并在体内转运及排出体外的过程（即药代动力学），以及其在体内产生的生物学效应（即药效动力学）。他们还将追踪运动、言语、功能能力和生物标志物的变化。

After completing 24 weeks of follow-up, patients may have the option to enter a long-term extension.

完成 24 周随访后，患者可能可以选择进入长期延长期。

In China, the LAUNCH ALS clinical trial is expected to enroll about 25 patients at Beijing Tiantan Hospital. Researchers led by principal investigator Yilong Wang, MD, PhD, will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of TRCN-1023.

在中国，LAUNCH ALS 临床试验预计将在北京天坛医院招募约 25 名患者。由首席研究者 Yilong Wang（MD、PhD）带领的研究人员将评估 TRCN-1023 的安全性、耐受性、药代动力学和药效动力学活性。

“The potency, durability and biological rationale behind TRCN-1023 make it a particularly exciting drug candidate to bring into the clinic,” said Wang, LAUNCH ALS principal investigator, executive vice president at Beijing Tiantan Hospital, and professor of neurology at Capital Medical University in Beijing. “I am proud to partner with the Trace Neuroscience and Tenacia Biopharmaceutical teams to advance this program and accelerate a potential new treatment for people with ALS worldwide.”

LAUNCH ALS 首席研究者、北京天坛医院常务副院长兼首都医科大学神经病学教授 Wang 表示：“TRCN-1023 的效力、持久性及其背后的生物学依据，使其成为一种特别令人振奋、值得推进临床试验的候选药物。我很荣幸能与 Trace Neuroscience 和 Tenacia Biopharmaceutical 团队合作推进该项目，并加快为全球 ALS 患者开发一种潜在的新疗法。”