一種令兒童迅速老化的疾病越來越接近治癒 (1/2)

Recently The New York Times on-line reported the following:

(Source: The New York Times)

A Disease That Makes Children Age Rapidly Gets Closer to a Cure (1/2)

The New York Times - By Gina Kolata

July 24, 2024, 5:00 a.m. ET

A cure for an ultrarare disease, progeria, could be on the horizon. The disease speeds up aging in children and dramatically shortens their lives. But, until recently, there was no path toward a highly effective treatment.

Now, a small group of academics and government scientists, including Dr. Francis Collins, the former director of the National Institutes of Health, is working with no expectation of financial gain to halt progeria in its tracks with an innovative gene editing technique.

If gene editing is effective in slowing or halting progeria, researchers say, the method may also help to treat other rare genetic diseases that have no treatments or cures and, like progeria, have aroused little interest from drug companies.

After a quarter-century of research, the group is approaching manufacturers and planning to seek approval from regulators for a clinical trial on progeria gene editing.

The project “has merit, but also risk,” said Dr. Kiran Musunuru, a gene editing researcher at the University of Pennsylvania, who also advises a gene editing company. He cautioned that although the editing worked well in mice, there is no guarantee that it will work in human patients.

Dr. Collins first became interested in progeria while he was training in medical genetics at Yale University in 1982, almost three decades before he was appointed to lead the N.I.H. One day, he saw a new patient, Meg Casey. She was less than four feet tall, hairless under her wig and wrinkled like an older woman. She was only in her 20s.

She had progeria.

Dr. Collins was saddened and moved. Almost nothing was known about the disease, which affects just one in 18 to 20 million people. According to the Progeria Research Foundation, there are only 18 known, living patients in the United States. While Ms. Casey and others have survived into their 20s, people with the disease often live to be only 14 or 15 years old, and many of them die from heart attacks or strokes.

“I thought, ‘Gosh, somebody should work on this,’” Dr. Collins recalled. “Then I went on to other things.”

Nineteen years later, Dr. Collins, who then headed a federal project to map the human genome, was at a party when he was approached by Dr. Scott Berns, a pediatric emergency room physician. He told Dr. Collins that his toddler, Sam, had a fatal disease.

“I don’t know if you’ve heard about it,” Dr. Berns said. “It’s called progeria.”

“I do know a little bit about it,” Dr. Collins replied.

He remembered Ms. Casey.

Dr. Collins invited Dr. Berns ; his wife, Dr. Leslie Gordon, a pediatrics resident; and 4-year-old Sam to his house. Dr. Collins spoke to Sam’s parents about the disease and played Frisbee with the boy. Sam lived to the age of 17.

Dr. Gordon told Dr. Collins she was under no illusions — the disease was a curiosity, but not a research priority because of its rarity. So she, Dr. Berns and her sister Audrey, a lawyer, established the Progeria Research Foundation to support promising studies.

“There was nothing else,” she said.

Dr. Collins was inspired. Although he was an administrator at the N.I.H., he also had a small lab and was free to study whatever he wanted. He decided to take on progeria.

But it took years, and the emergence of a new era of molecular medicine with advances in gene editing, for the prospect of a cure for progeria to seem possible.

The new types of gene editing are “potentially the answer to a dream we all want to come true,” Dr. Collins said. “There are roughly 7,000 genetic diseases for which we know the mutation.”

Of these genetic diseases, 85 percent are ultrarare, affecting fewer than one in a million people.

And among them, Dr. Collins said, “only a few hundred have treatments.”

(to be continued)

Translation

治療一種極為罕見的疾病 - 早衰症- 可能即將出現。這種疾病會加速兒童的衰老並大大縮短他們的壽命。但是，直到最近，還沒有找到高效率的治療方法。

現在，一小群學者和政府科學家，包括美國國立衛生研究院 (NIH)前院長 Francis Collins 博士，在不期望經濟收益的情況下，正透過一種創新的基因編輯技術來阻止早衰症的發展。

研究人員表示，如果基因編輯能有效減緩或阻止早衰症，那麼這種方法也可能有助於治療其他沒有治療方法或治癒方法的罕見遺傳疾病，例如早衰症，都是製藥公司不感興趣的。

經過四分之一個世紀的研究，該小組正在與製造商接洽，並計劃尋求監管機構批准進行早衰基因編輯的臨床試驗。

賓州大學基因編輯研究員 Kiran Musunuru 博士說，該計劃 “有優點，但也有風險”，他也為一家基因編輯公司提供諮詢。他警告說，雖然編輯在小鼠身上效果很好，但不能保證它也適用於人類患者。

Collins博士於 1982 年在耶魯大學接受醫學遺傳學培訓時首次對早衰症產生了興趣，大約三十年後，他被任命為 國立衛生研究院負責人。有一天，他見到了一位新病人，Meg Casey。她身高不到四英尺，假髮下沒有頭髮，滿臉皺紋，像個年長的女人。她才20多歲。

她患有早衰症。

Collins 博士既悲傷又感動。人們對這種疾病幾乎一無所知，這種疾病只影響 1800 萬 至 2000 萬人中的一個。據早衰症研究基金會稱，美國已知的活著的患者只有 18 名。雖然Casey女士和其他人都活到了 20 多歲，但患有這種疾病的人通常只能活到 14 或 15 歲，其中許多人死於心臟病或中風。

Collins 博士回憶道: 「我想，『啊呀，應該有人研究這個吧』」; 「然後我就去做其他事情了」。

十九年後，當時負責繪製人類基因組圖譜的聯邦計畫的 Collins 博士正在參加一個聚會，兒科急診室醫生 Scott Berns 找到了他。他告訴 Collins 博士，他的孩子 Sam 患有致命的疾病。

Berns 醫生說: 「我不知道你是否聽說過」; 「這就是所謂的早衰症」。

Collins 博士回答: 「我確實知道一點點」。

他記得 Casey 女士。

Collins 博士邀請了 Berns 醫生及他的妻子 Leslie Gordon 醫生, 是一名兒科住院醫生；和 4 歲的 Sam 到他家。Collins 博士向 Sam 的父母講述了這種疾病，並與男孩一起玩飛盤。Sam 活到了17歲。

Gordon 醫生告 Collins 博士，她並不抱持任何幻想 - 這種疾病引出一種好奇心，但由於其稀有性而不是研究重點。因此，Gordon 醫生、Berns醫生 和她的律師妹妹 Audrey 建立了早衰症研究基金會來支持有前景的研究。

她說:“ 除此之外再沒有別的事可做”。

Collins 博士受到了啟發。雖然他是國家衛生研究院的行政人員，但他也有一個小實驗室，可以自由地研究他想研究的任何東西。他決定對抗早衰症。

但這需要數年時間，隨著基因編輯技術的進步，分子醫學新時代的出現，治癒早衰症的前景似乎成為可能。

Collins 博士說，新型基因編輯「可能是我們都想去實現的夢想的答案」。 「我們知道大約 7,000 種遺傳疾病的突變」。

在這些遺傳疾病中，85% 是極為罕見的，影響的人數不到百萬分之一。

Collins 博士說，其中「只有幾百種有方法治療」。

（待續）

Note:

1. Progeria (早年衰老症候群,簡稱早衰症) also known as Hutchinson-Gilford progeria syndrome, is an extremely rare, progressive genetic disorder. It causes children to age rapidly, starting in their first two years of life. Children with progeria generally appear healthy at birth. During the first year, symptoms such as slowed growth, loss of fat tissue and hair loss begin to appear. Heart problems or strokes are the eventual cause of death in most children with progeria. The average life expectancy for a child with progeria is about 15 years. Some with the condition may die younger and others may live longer, even to about 20 years. (https://www.mayoclinic.org/diseases-conditions/progeria/symptoms-causes/syc-)

2. Francis Sellers Collins ForMemRS (Fellowship of the Royal Society) is an American physician-scientist who discovered the genes associated with a number of diseases and led the Human Genome Project. Before being appointed director of the NIH, Collins led the Human Genome Project and other genomics research initiatives as director of the National Human Genome Research Institute (NHGRI), one of the 27 institutes and centers at NIH. Before joining NHGRI, he earned a reputation as a gene hunter at the University of Michigan. He has been elected to the Institute of Medicine and the National Academy of Sciences, and has received the Presidential Medal of Freedom and the National Medal of Science. (Wikipedia)