來自弗吉尼亞大學(xué)衛(wèi)生系統(tǒng)的兩個醫(yī)生首次發(fā)現(xiàn)消除肌肉細(xì)胞內(nèi)毒性的RNA（核糖核酸）從而可以治愈強(qiáng)直型肌肉營養(yǎng)不良,，這種疾患在成人身上經(jīng)常發(fā)生的最普遍的肌肉營養(yǎng)不良,。
??在美國大學(xué)有40,000人患有肌強(qiáng)直性肌營養(yǎng)不良（MMD）.這種疾患可以導(dǎo)致慢性持續(xù)性的肌肉萎縮，心率不齊,，白內(nèi)障以及胰島素耐受,。很多人知道他們一二十歲才被診斷患有MMD。
??為了證明在MMD疾病中涉及到毒性RNA這種理論,，來自弗吉尼亞大學(xué)（UV）病理學(xué)家Mani Mahadevan博士領(lǐng)導(dǎo)的研究團(tuán)隊在小鼠中重現(xiàn)了這種疾病,。Mahadevan談到：“在我們的小鼠動物模型中，用毒性RNA處理小鼠,，使得它們患各種類型肌強(qiáng)直性營養(yǎng)不良,。這時如果你消除毒性RNA，患病的小鼠可以恢復(fù)正常”,。
??Mahadevan希望該研究可以在未來的幾年內(nèi)引導(dǎo)治療MMD的新療法,。Mahadevan談到：“如果我們研制一種療法來沉默毒性RNA分子的表達(dá)。那么我們將有能找到治療MMD的方法”,。Mahadevan的研究出版在2006年9月份這期的《自然－遺傳學(xué)》雜志上,。
??DNA轉(zhuǎn)變成蛋白過程中，RNA的合成是處在第二步,。這些蛋白決定在機(jī)體細(xì)胞中發(fā)揮什么功能,。MMD是第一個由毒性RNA引起的疾患。
??在1992年,，Mahadevan發(fā)現(xiàn)了引起MMD（Ⅰ型）的基因突變,。突變是發(fā)生在一個叫DMPK基因中出現(xiàn)大量的CTG的重復(fù)序列。每一個MMD的患者在19號染色體發(fā)生突變,，現(xiàn)在也將這作為肌強(qiáng)直性營養(yǎng)不良的遺傳診斷指標(biāo)之一,。
??在他們最近的研究中，Mahadevan和他的同僚建立了一種新型的含有額外多個拷貝CTG重復(fù)序列的小鼠動物模型,，而且每一個結(jié)合到DNA的蛋白都能在顯微鏡下發(fā)綠光,。他們同時在小鼠身上整合了對于MMD的開關(guān)，可以通過在飲水中給予它們強(qiáng)力霉素來激活,。
??當(dāng)小鼠開始產(chǎn)生多拷貝帶有CTG的RNA時,，在幾周內(nèi)它們就出現(xiàn)很多Ⅰ型MMD的癥狀，包括不能自由的肌肉放松以及心率失常,。當(dāng)終止強(qiáng)力霉素的給予時,，小鼠就停止產(chǎn)生毒性RNA并恢復(fù)正常，除了在當(dāng)心臟受到嚴(yán)重傷害的情況下不能恢復(fù)。
??然而,，迄今為止Mahadevan和其他科學(xué)家都不能準(zhǔn)確地解釋在細(xì)胞內(nèi)引起某些人患肌強(qiáng)直性肌營養(yǎng)不良,。Mahadevan認(rèn)為：“目前盛行的理論認(rèn)為RNA是停留在核內(nèi),，而不是被移出來,，蛋白要黏附RNA上，而不能發(fā)揮他們的功效”,。
??Mahadevan said認(rèn)為：“在機(jī)體的每一個細(xì)胞并不能都發(fā)現(xiàn)毒性RNA,，然而它在肌肉、心臟和大腦細(xì)胞中有很高的水平,，以及在腸道的褶上,、晶狀體和眼肌肉細(xì)胞內(nèi)也是如此。
英文原文：
Toxic molecule may cause most common type of muscular dystrophy
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Dr. Mani Mahadevan
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Doctors at the University of Virginia Health System have shown for the first time that getting rid of poisonous RNA (ribonucleic acid) in muscle cells can reverse myotonic dystrophy, the most common type of muscular dystrophy in adults.
About 40,000 people in the United States have myotonic muscular dystrophy (MMD). The disease can cause a slow, progressive wasting of the muscles, irregular heartbeat, cataracts and insulin resistance. Many people don't know they have MMD until their teens or twenties.
To prove the theory that toxic RNA is involved in myotonic muscular dystrophy, a research team led by Dr. Mani Mahadevan, a UVa pathologist, duplicated the disease in mice. "We showed in our mouse model that when you make this poisonous RNA the mice get various aspects of myotonic dystrophy," Mahadevan said. "Then, when you take away the toxic RNA, the mice get back to normal."
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A myotonic mouse muscle with green florescent protein.
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Mahadevan hopes the research might lead to new therapies for MMD in the next few years. "If we develop a therapy to silence the expression of the toxic RNA molecule, that would be a viable approach to treat people with myotonic muscular dystrophy," he said. Mahadevan's research in published in the September 2006 issue of Nature Genetics and can be found online at: http://www.nature.com/ng/index.html
Making RNA is the second step in the conversion of DNA into proteins that determine the function of the body's cells. Myotonic muscular dystrophy is the first example of a disease caused by toxic RNA.
In 1992, Mahadevan discovered the gene mutation that causes myotonic muscular dystrophy (type 1) as part of a research group in Canada. The mutation is an increased number of CTG repeats in a gene called DMPK. Everyone with myotonic muscular dystrophy has that mutation on chromosome 19, which is now part of a genetic, diagnostic test for myotonic dystrophy.
In their latest research, Mahadevan and colleagues created a new type of mouse model with many extra copies of the CTG repeats, each attached to DNA for a protein that glows green under a microscope. They also integrated an "on switch" for MMD in the mice, activated by giving them doxycycline, an antibiotic, in their drinking water.
When mice began to produce many copies of RNA with CTG repeats, they developed the hallmarks of type 1 MMD within a few weeks, including an inability to relax muscles and heart rhythm abnormalities. When doxycycline was stopped, mice stopped producing toxic RNA and returned to normal, except in cases when the heart was severely damaged.
So far, however, Mahadevan and other scientists can't explain exactly what happens inside the cell to cause someone to get myotonic dystrophy. "The prevailing theory is that the RNA remains in the nucleus, rather than moving out of it, and proteins get stuck to the RNA and aren't able to do their job," Mahadevan said.
This toxic RNA in not found in every cell of body, Mahadevan said. Rather, it is produced in higher levels in muscle cells, in the heart and brain, in the lining of the intestines and in the lens and muscles of the eyes.
