Scientific investigation into the world’s second man cleared of the AIDS virus is zooming in on a gene and a treatment side-effect, as newly-enthused researchers strive to find a cure for the disease that has killed millions.
Known as the “London Patient,” the man had HIV and a type of blood cancer called Hodgkin’s lymphoma. He responded successfully to a bone marrow transplant from a donor with rare genetic resistance to HIV infection. The transplant cleared the man’s cancer and his HIV, but the resistant genes may not be the sole cause of his HIV remission.
The London Patient’s case gives fresh hope to scientists and pharmaceutical researchers who have spent decades looking for ways to end AIDS. HIV expert Sharon Lewin said two factors were probably at play in his success story: the genetic resistance and a transplant side-effect that attacks immune cells.
Photo: Reuters
照片:路透
“The new bone marrow is resistant to HIV, and also the new bone marrow is actively eliminating any HIV-infected cells through something called ‘graft versus host’ disease,” said Lewin, co-chair of the International AIDS Society’s cure research advisory board and a researcher at Australia’s Doherty Institute.
The London Patient joins the first case of this kind, Timothy Ray Brown — or the “Berlin Patient” — whose HIV was eradicated by a similar transplant treatment in 2007. It involved the destruction of his immune system and transplanted stem cells with a gene mutation called CCR5 that resists HIV.
The AIDS virus uses CCR5 to enter cells, but if the gene is mutated, HIV cannot latch onto cells and infect them. This “graft versus host” effect is akin to a deadly battle of two immune systems, explained Steven Deeks, an HIV expert at the University of California. The incoming transplanted donor-immune cells seek out and destroy all the host’s immune cells — including those in which HIV can hide out, he said.
“The transplant resulted in the complete destruction of the old immune system and the construction of a new immune system in which the (HIV) virus can’t replicate (because of the genetic mutation). That is the cure,” Deeks told Reuters. But such transplants are complex, expensive and highly risky to the patients, who would run a risk of dying in the process.
Some research teams in the US and elsewhere are developing gene-editing techniques to edit CCR5 cells outside of the body and reintroduce the edited cells back to patients. Specialists said this method has its limits, because it only edits some cells and leaves native wild type cells untouched in the body where HIV can still hide.
Other avenues are also being explored. Dan Barouch, a vaccine researcher at the Harvard-affiliated Beth Israel Deaconess Medical Center in Boston, is working with the pharmaceutical company Gilead Sciences to develop what’s known as a “kick and kill” treatment. The idea is to use an initial drug to flush out HIV that is hiding from the immune system and then use standard antiretrovirals to kill the newly-exposed virus. Animal studies have shown hope, but it has not yet been proven in people.
“All HIV cure approaches in general are in their infancy,” he said in a telephone interview. Rare cases of remission, such as the London and Berlin patients “provide a lot of enthusiasm and motivation” for research teams and show that a cure can be achieved, he said, “but we still have a long way to go.”
(Reuters)
日前全球出現第二例愛滋病患,體內已完全檢驗不到俗稱愛滋病的後天免疫缺乏症候群病毒,讓研究人員重新燃起熱情,力圖找到解藥,治癒這種已奪走數百萬條生命的疾病。對該病例進行研究後,科學家開始聚焦於某個基因和一項療法的副作用上。
這起病例被稱為「倫敦病人」,他曾感染人類免疫缺乏病毒(HIV,俗稱愛滋病毒),還患有一種血癌,稱為何杰金氏淋巴瘤。該名病患後來接受骨髓移植,術後反應良好,而捐贈者帶有罕見的基因變異,能夠抵抗愛滋病毒感染,這場骨髓移植遂完全清除他的癌症和愛滋病毒。不過,抗病基因並不完全是使他愛滋病毒感染獲得「緩解」的唯一原因。
科學家和藥學研究人員已花費數十年的心力,尋找終結愛滋病的方法,而「倫敦病人」這個病例帶給他們嶄新的希望。愛滋病毒專家夏倫‧呂因表示,有兩項因素或許在該成功案例中發揮了作用:也就是基因抗病能力,以及移植手術攻擊免疫細胞的副作用。
呂因擔任國際愛滋病學會解藥研究諮詢委員會的副主席,同時也是澳洲杜赫蒂研究院的研究員,她指出:「新骨髓能抵抗愛滋病毒,而它同時也藉由一種稱作『移植物對抗宿主疾病』的方式,主動消滅任何受愛滋病毒感染的細胞。」
「倫敦病人」是這類情況的第二例,第一例是提莫西‧雷‧布朗──或稱「柏林病人」──他在二○○七年接受一場類似的移植手術,體內的愛滋病毒從此被完全消滅。這個過程包含破壞他的免疫系統,而移植的幹細胞帶有CCR5蛋白質(趨化因子受體5)的基因突變,能夠抵抗愛滋病毒。
愛滋病毒利用CCR5蛋白質來進入細胞,但是一旦控制該蛋白質的基因產生突變,愛滋病毒就無法佔領細胞,進而感染。加州大學的愛滋病毒專家史蒂芬‧迪克斯解釋說,「移植物對抗宿主」效果近似於兩個免疫系統之間發動你死我活的戰鬥。他表示,經移植來到體內的捐贈者免疫細胞,會找出宿主所有的免疫細胞,並且悉數摧毀──其中包括那些可供愛滋病毒躲藏的細胞。
迪克斯向路透表示:「移植手術導致舊的免疫系統完全遭到摧毀,同時又建立起新的免疫系統,愛滋病毒(由於基因突變)無法於其中複製,這就是解方。」然而,像這樣的移植手術既複雜又所費不貲,對病人而言又具高度風險,病人很可能在過程中喪命。
美國和其他國家的研究團隊目前正在研發基因編輯技術,試圖在體外編輯CCR5細胞,再將編輯後的細胞重新引入病人體內。專家認為,這個方法仍有其侷限性,因為它只會編輯某些細胞,體內原生的野生型細胞則不受影響,愛滋病毒仍可躲藏其中。
科學家也在探索其它途徑。疫苗研究學家丹‧巴魯克,服務於隸屬哈佛大學的波士頓貝斯以色列女執事醫療中心,目前正在和藥廠 吉利德科學公司合作,研發所謂的「踢出並殺死」療法。其概念是使用一種初期藥物,把躲在免疫系統裡的愛滋病毒通通趕出來,然後再用正規的抗反轉錄病毒藥物,殺死新暴露出來的病毒。該療法已在動物實驗中展現可能性,但目前還未於人體證實。
在電話訪談中,巴魯克指出:「目前所有治癒愛滋病毒的方法,基本上都還在發展初期。」像倫敦病人和柏林病人這類罕見的「緩解」病例,對研究團隊而言「確實激發許多研究熱忱和動力」,而且顯示愛滋病解藥是可能達成的,他說,「但是我們還有很長的一段路要走。」
(台北時報章厚明譯)
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