據(jù)統(tǒng)計(jì),全球帕金森氏病的患者已經(jīng)超過(guò)1000萬(wàn)人,其中近100萬(wàn)人在美國(guó)。目前尚無(wú)獲批的治療方案,,病患唯一的選擇就是使用抑制退行性病變的藥物,而不是根治其病,。
如今,,一群科學(xué)家希望通過(guò)研究實(shí)驗(yàn)室培養(yǎng)的迷你人腦來(lái)實(shí)現(xiàn)突破,從而加速帕金森氏病的研究和藥物開發(fā),。在首次發(fā)表于《神經(jīng)病學(xué)年鑒》(Annals of Neurology)7月刊的一篇研究中,,科學(xué)家使用這些合成迷你大腦來(lái)模仿正常人類中腦的活動(dòng),而中腦對(duì)于受帕金森氏病影響的肌肉運(yùn)動(dòng),、視覺和聽覺處理至關(guān)重要,。
本質(zhì)上,研究人員再現(xiàn)了真正人腦在出現(xiàn)某種腦疾病具有的所有風(fēng)險(xiǎn)因素后會(huì)發(fā)生的狀況,,而這個(gè)實(shí)驗(yàn)中的腦病就是帕金森氏病,。這一點(diǎn)是異常重要的,因?yàn)檫@種疾病的藥物開發(fā)在當(dāng)前使用的是老鼠大腦,,與人腦相比可能會(huì)產(chǎn)生不同的結(jié)果,。例如,老鼠體內(nèi)不會(huì)出現(xiàn)人類的某些生物性損耗,,而帕金森氏病研發(fā)的老鼠模型可能不會(huì)出現(xiàn)與該病相關(guān)的生物副產(chǎn)品,。
該研究的高級(jí)合著者,、新加坡科技研究局(Agency for Science, Technology and Research)旗下的生物醫(yī)療研究理事會(huì)(Biomedical Research Council)的Ng Huck Hui表示:“在動(dòng)物實(shí)驗(yàn)中重新打造帕金森氏病的模型十分困難,因?yàn)檫@些模型無(wú)法展現(xiàn)帕金森氏病的一個(gè)重要特征——漸進(jìn)性,、選擇性的神經(jīng)元損失,,而神經(jīng)元負(fù)責(zé)分泌神經(jīng)遞質(zhì)多巴胺?!?/p>
無(wú)法直接訪問(wèn)大腦以及神經(jīng)系統(tǒng)的復(fù)雜性是大腦藥物開發(fā)難度如此之大的首要原因,。例如,美國(guó)食品與藥物管理局(Food and Drug Administration)批準(zhǔn)的最后一種帕金森氏病藥物是2019年日本藥企協(xié)和麒麟(Kyowa Kirin)的Nourianz,,而且這種藥物是用于搭配另一種控制癥狀的藥物使用,,并非治療該疾病。
希望在于,,加深對(duì)帕金森氏病患大腦狀況的了解將有助于解構(gòu)疾病,,并推動(dòng)藥物開發(fā)。研究人員通過(guò)培養(yǎng)生成神經(jīng)元的干細(xì)胞,,打造了豌豆大小的迷你大腦,。他們通過(guò)對(duì)干細(xì)胞的基因進(jìn)行調(diào)整,來(lái)修改這一基于人類的迷你大腦,,進(jìn)而模擬了更易出現(xiàn)帕金森氏病的基因組的特性,。
在美國(guó),帕金森氏病是僅次于阿爾茨海默癥,、排名第二位的常見神經(jīng)退行性疾病。在這一研究中,,研究人員僅專注于帕金森氏病,。然而,他們希望其合成的基因模板可以用于未來(lái)各類大腦疾病的研究,。
該研究的研究人員來(lái)自于新加坡科技研究局旗下的基因研究所(Genome Institute of Singapore),、新加坡國(guó)立腦神經(jīng)科學(xué)研究所(National Neuroscience Institute),以及杜克-新加坡國(guó)立大學(xué)醫(yī)學(xué)院(Duke-NUS Medical School),。(財(cái)富中文網(wǎng))
譯者:馮豐
審校:夏林
據(jù)統(tǒng)計(jì),,全球帕金森氏病的患者已經(jīng)超過(guò)1000萬(wàn)人,其中近100萬(wàn)人在美國(guó),。目前尚無(wú)獲批的治療方案,,病患唯一的選擇就是使用抑制退行性病變的藥物,而不是根治其病,。
如今,,一群科學(xué)家希望通過(guò)研究實(shí)驗(yàn)室培養(yǎng)的迷你人腦來(lái)實(shí)現(xiàn)突破,從而加速帕金森氏病的研究和藥物開發(fā),。在首次發(fā)表于《神經(jīng)病學(xué)年鑒》(Annals of Neurology)7月刊的一篇研究中,,科學(xué)家使用這些合成迷你大腦來(lái)模仿正常人類中腦的活動(dòng),,而中腦對(duì)于受帕金森氏病影響的肌肉運(yùn)動(dòng)、視覺和聽覺處理至關(guān)重要,。
本質(zhì)上,,研究人員再現(xiàn)了真正人腦在出現(xiàn)某種腦疾病具有的所有風(fēng)險(xiǎn)因素后會(huì)發(fā)生的狀況,而這個(gè)實(shí)驗(yàn)中的腦病就是帕金森氏病,。這一點(diǎn)是異常重要的,,因?yàn)檫@種疾病的藥物開發(fā)在當(dāng)前使用的是老鼠大腦,與人腦相比可能會(huì)產(chǎn)生不同的結(jié)果,。例如,,老鼠體內(nèi)不會(huì)出現(xiàn)人類的某些生物性損耗,而帕金森氏病研發(fā)的老鼠模型可能不會(huì)出現(xiàn)與該病相關(guān)的生物副產(chǎn)品,。
該研究的高級(jí)合著者,、新加坡科技研究局(Agency for Science, Technology and Research)旗下的生物醫(yī)療研究理事會(huì)(Biomedical Research Council)的Ng Huck Hui表示:“在動(dòng)物實(shí)驗(yàn)中重新打造帕金森氏病的模型十分困難,因?yàn)檫@些模型無(wú)法展現(xiàn)帕金森氏病的一個(gè)重要特征——漸進(jìn)性,、選擇性的神經(jīng)元損失,,而神經(jīng)元負(fù)責(zé)分泌神經(jīng)遞質(zhì)多巴胺?!?/p>
無(wú)法直接訪問(wèn)大腦以及神經(jīng)系統(tǒng)的復(fù)雜性是大腦藥物開發(fā)難度如此之大的首要原因,。例如,美國(guó)食品與藥物管理局(Food and Drug Administration)批準(zhǔn)的最后一種帕金森氏病藥物是2019年日本藥企協(xié)和麒麟(Kyowa Kirin)的Nourianz,,而且這種藥物是用于搭配另一種控制癥狀的藥物使用,,并非治療該疾病。
希望在于,,加深對(duì)帕金森氏病患大腦狀況的了解將有助于解構(gòu)疾病,,并推動(dòng)藥物開發(fā)。研究人員通過(guò)培養(yǎng)生成神經(jīng)元的干細(xì)胞,,打造了豌豆大小的迷你大腦,。他們通過(guò)對(duì)干細(xì)胞的基因進(jìn)行調(diào)整,來(lái)修改這一基于人類的迷你大腦,,進(jìn)而模擬了更易出現(xiàn)帕金森氏病的基因組的特性,。
在美國(guó),帕金森氏病是僅次于阿爾茨海默癥,、排名第二位的常見神經(jīng)退行性疾病,。在這一研究中,研究人員僅專注于帕金森氏病,。然而,,他們希望其合成的基因模板可以用于未來(lái)各類大腦疾病的研究。
該研究的研究人員來(lái)自于新加坡科技研究局旗下的基因研究所(Genome Institute of Singapore),、新加坡國(guó)立腦神經(jīng)科學(xué)研究所(National Neuroscience Institute),,以及杜克-新加坡國(guó)立大學(xué)醫(yī)學(xué)院(Duke-NUS Medical School),。(財(cái)富中文網(wǎng))
譯者:馮豐
審校:夏林
Upwards of 10 million people globally and nearly 1 million in the United States live with Parkinson's disease, which has no approved treatments. The only option for patients is drugs that can keep the degenerative condition in check, rather than tackle its root causes.
A group of scientists now wants to upend that dynamic by leveraging lab-grown, human mini-brains to spur Parkinson's research and drug development. In a study first published in the July edition of the journal Annals of Neurology, scientists used these synthetic mini-brains to mimic the activity of a regular human midbrain, which is critical to muscle movement and visual and auditory processing affected by Parkinson's disease.
In essence the researchers replicated what an actual human brain would go through if it carried all the risk factors for a certain brain disease, in this case Parkinson's. That's particularly important since drug development for the disease must currently be done using mouse brains, which may produce different results than when using those of humans. For instance, certain biological wear and tear doesn't manifest in a mouse, and a mouse model in Parkinson's R&D may not produce the kinds of biological by-products linked with the disease.
"Re-creating models of Parkinson’s disease in animal models is hard, as these do not show the progressive and selective loss of neurons that produce the neurotransmitter dopamine, a major feature of Parkinson’s disease," said Ng Huck Hui of the Agency for Science, Technology and Research's Biomedical Research Council and the study's senior coauthor.
The inability to directly access the brain and the complexity of the nervous system are key reasons brain drugs are so hard to create. To wit: The last Parkinson's treatment approved by the Food and Drug Administration (FDA) was Kyowa Kirin's Nourianz in 2019, and that was as a therapy added on to another one that controls symptoms rather than the disease.
The hope is that a better understanding of what a Parkinson's disease patient's brain goes through will make it easier to deconstruct the illness and spur drug development.The researchers created the pea-size mini-brains by growing stem cells that create neurons. They were able to modify this human-based mini-brain with genetic tweaks to the stem cells that, in turn, mimicked the genomic qualities associated with a higher risk for Parkinson's.
For this study, the researchers focused only on Parkinson's, the second-most common neurodegenerative condition in the U.S. and second only to Alzheimer's. But they hope that their synthetic, genetic template can be used in all manner of future brain disease research.
The study was conducted by researchers from the Agency of Science, Technology and Research's Genome Institute of Singapore, Singapore's National Neuroscience Institute, and Duke-NUS Medical School.