Third Rock Ventures, the well-known backer of biotechnology companies, is leading a nine-figure fundraising round for a startup that aims to treat ALS by replacing broken genetic machinery.

著名的生物技术公司支持者Third Rock Ventures正在为一家旨在通过更换损坏的基因机器来治疗ALS的初创公司领导一轮9位数的融资。

The startup, Trace Neuroscience, launched Tuesday with $101 million from an investment group that includes Atlas Venture, RA Capital Management and Alphabet’s venture capital arm, GV. Third Rock led the round and two of its partners, Jeffrey Tong and Dodzie Sogah, will sit on the company’s seven-member board of directors..

这家名为Trace Neuroscience的初创公司于周二成立，投资集团斥资1.01亿美元，其中包括Atlas Venture、RA Capital Management和Alphabet的风险投资部门GV。Third Rock领跑了这一轮，其两名合伙人Jeffrey Tong和Dodzie Sogah将担任该公司七名董事会成员。。

Based in the San Francisco area, Trace’s research centers on a molecule essential for processing RNA — the snippets of genetic code that tell cells what proteins to make. If RNA is like an instruction manual, then this “TDP-43” molecule helps write the text, cut the pages and bind the book.

Trace位于旧金山地区，其研究中心是一种加工RNA所必需的分子，即告诉细胞要制造什么蛋白质的遗传密码片段。如果RNA就像一本说明书，那么这个“TDP-43”分子可以帮助书写文本、剪切页面和装订书籍。

But TDP-43 can sometimes mutate, causing it to become dysfunctional or stop working altogether. That, in turn, impairs the production of key proteins. Over the past several years, scientists believe they’ve uncovered how this problem connects to nerve-destroying disorders. In amyotrophic lateral sclerosis, for example, research suggests that when there isn’t enough TDP-43 in the core of nerve cells, it leads to incorrect splicing of the genetic instructions for a protein those cells need to communicate..

但TDP-43有时会发生突变，导致其功能失调或完全停止工作。这反过来又会损害关键蛋白质的产生。在过去几年中，科学家们相信他们已经发现了这个问题与神经破坏性疾病的关系。例如，在肌萎缩性侧索硬化症中，研究表明，当神经细胞核心中没有足够的TDP-43时，它会导致这些细胞需要交流的蛋白质的基因指令的错误剪接。。

That protein is called UNC13A, with the first half of the name a shortened form of the word uncoordinated. Its discovery dates back to the 1970s, when a genetic screening of ringworms found that those with mutated UNC13A moved more erratically or were paralyzed. About 15 years ago, human genomic studies then determined that changes to this protein are a risk factor for ALS as well as a rarer type of dementia..

这种蛋白质被称为UNC13A，名字的前半部分是单词uncoordinated的缩写。它的发现可以追溯到20世纪70年代，当时对癣虫进行的基因筛查发现，UNC13A突变的癣虫运动更加不稳定或瘫痪。大约15年前，人类基因组研究确定，这种蛋白质的变化是ALS的危险因素，也是一种罕见的痴呆症。。

To address this problem, Trace has been working on a type of drug known as an antisense therapy, which the company designed to bind to the instructions for UNC13A and ensure they’re properly processed. To date, the Food and Drug Administration has approved more than a dozen antisense therapies across a range of diseases.

为了解决这个问题，Trace一直在研究一种被称为反义疗法的药物，该公司设计该药物与UNC13A的说明书结合，并确保它们得到正确处理。迄今为止，美国食品和药物管理局已经批准了一系列疾病的十几种反义疗法。

The first one for ALS — sold by Biogen under the brand name Qalsody — became available last year, though only for the small percentage of patients who have mutations in a different gene..

第一个用于ALS的药物由Biogen以品牌Qalsody出售，去年上市，但仅适用于少数具有不同基因突变的患者。。

Trace is led by Eric Green, a cardiologist-turned-entrepreneur who helped launch and build multiple Third Rock portfolio companies. Green co-founded and served as chief scientific officer of Maze Therapeutics, a San Francisco-based precision medicine company that debuted in 2019. He was also head of translational research at MyoKardia, a drug developer that focused on genetic forms of heart disease and was acquired by Bristol Myers Squibb in 2020 for $13 billion..

Trace由埃里克·格林（EricGreen）领导，埃里克是一位心脏病专家，后来成为企业家，他帮助创办了多家第三摇滚投资组合公司。格林与人共同创立并担任Maze Therapeutics的首席科学官，Maze Therapeutics是一家总部位于旧金山的精准医学公司，于2019年首次成立。他还是MyoKardia转化研究的负责人，MyoKardia是一家专注于心脏病遗传形式的药物开发公司，于2020年被百时美施贵宝以130亿美元收购。。

Green said that, while at Maze, a central question facing his team was: which diseases could benefit most from genetic medicines. ALS, which had some well-established genetic targets, “came to the top of our list.” Green then started working with Aaron Gitler, a Stanford University professor whose research attempts to identify the root causes of neurodegenerative diseases..

格林说，在梅兹，他的团队面临的一个中心问题是：哪些疾病可以从基因药物中获益最多。ALS具有一些公认的遗传靶标，“位居我们的榜首。”然后，格林开始与斯坦福大学教授亚伦·吉特勒（AaronGitler）合作，吉特勒（AaronGitler）的研究试图确定神经退行性疾病的根本原因。。

By 2022, Gitler’s lab and two others — those of Pietro Fratta, a professor of cellular and molecular neuroscience at University College London; and Michael Ward, a senior investigator in the National Institutes of Health’s neurological disorders division — had made concurrent discoveries about the ties between UNC13A and TDP-43.

到2022年，吉特勒的实验室和另外两个实验室——伦敦大学学院细胞和分子神经科学教授彼得罗·弗拉塔的实验室；美国国立卫生研究院神经疾病部门的高级研究员迈克尔·沃德（MichaelWard）同时发现了UNC13A和TDP-43之间的联系。

And it was those discoveries that convinced Green and Third Rock a drug company should be formed..

正是这些发现使Green和Third Rock确信应该成立一家制药公司。。

“That was the ‘aha’ moment for us,” said Tong, of Third Rock.

“这对我们来说是‘啊哈’时刻，”第三石的Tong说。

Green brought the three researchers in as co-founders. Then, he turned his attention to funding.

格林将这三位研究人员作为联合创始人请来。然后，他把注意力转向了资金。

According to Green, Trace sought to raise enough money to get through “key clinical data points.” The startup has just one drug program, which it says is on track to enter human testing in early 2026. The program’s initial target will be ALS, though Trace believes UNC13A restoration could be useful for treating other neurodegenerative illnesses as well..

根据格林的说法，Trace试图筹集足够的资金来获得“关键临床数据点”。这家初创公司只有一个药物项目，它表示有望在2026年初进入人体测试。该计划的最初目标是ALS，尽管Trace认为UNC13A修复也可能对治疗其他神经退行性疾病有用。。

Green said he expects Trace’s program to benefit from the prior work done on Qalsody. Biogen’s medicine won approval because patients given it experienced significant reductions in a protein connected to nerve cell damage. ALS drugmakers have since made this protein, “neurofilament light chain,” a key part of their development plans..

格林说，他预计Trace的项目将从之前在Qalsody上所做的工作中受益。Biogen的药物获得了批准，因为服用该药物的患者经历了与神经细胞损伤有关的蛋白质的显着减少。ALS制药商已经将这种蛋白质“神经丝轻链”作为其开发计划的关键部分。。

“That gives us a much stronger toolkit for evaluating our molecules than we had before,” Green said.

格林说：“这为我们评估分子提供了比以前更强的工具包。”。

The Qalsody saga is also encouraging from an investor standpoint, according to Tong. Neuroscience is a notoriously difficult area of drug development; in ALS alone, many promising treatments have fizzled out in clinical testing over the past several years. That can make the argument for investing in brain research harder..

Tong表示，从投资者的角度来看，Qalsody的传奇故事也令人鼓舞。神经科学是众所周知的药物开发困难领域；仅在ALS中，许多有希望的治疗方法在过去几年的临床试验中都失败了。这可能会使投资大脑研究的论点变得更加困难。。

But with the Qalsody example, “all of a sudden it makes the company creation side of this and the clinical proof of concept — so what does it take to actually prove that we have something important — much more feasible,” Tong said.

但以Qalsody为例，“突然之间，它使公司的创建和临床概念验证变得更加可行，那么需要什么才能真正证明我们有一些重要的东西，”Tong说。