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zoom RSS 脊髄電気刺激によるパーキンソン病の治療

<<   作成日時 : 2009/03/21 12:44   >>

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画像 齧歯類の脊髄を電気刺激することによって、パーキンソン病の最も悪い徴候のいくつかが改善した。穏やかな電流が脊髄上と脳の中に流れている間、正常であるかのように、動物は、かごのまわりではね回る能力を取り戻す。
 研究者は、深部脳刺激という直接的な刺激への代案となりうるだろうと言う。症状の強い患者の30%が治療の適応となる。脊髄刺激はより安全でより侵襲性がなく、病気治療に必要な薬の量を減らせる可能性があると言う。現在猿で試験中であり、成功すれば人の臨床試験がその後数年で始まるだろう。
 クリーブランド・クリニックのDr. Ali Rezaiは、脊髄刺激が「技術的には簡単」であり、慢性疼痛、痙性、脳卒中などの医学的問題を治療するために数万人の人々について実行されたと言う。主な副作用は、決して、休止しないピンと針のような振動の感覚であるという。
 パーキンソン病は、ドーパミン(正常な動きに必須の脳化学物質)を分泌する細胞の消失に起因している。患者は、震え、堅い姿勢、バランスの障害、および動き出し難さが進行する。米国で、少なくとも50万人がパーキンソン病に苦しむと推計され、約50,000人が毎年新たに報告される。治療の第1選択は、L-ドーパである。直接的な脳深部刺激は、ドーパミン伝播に関係する脳部位をねらうことで症状を弱める。
 新しい治療においては、脳ドーパミンが枯渇した動物に小さい電極(手指のつめのサイズ)を脊髄の上に移植された。穏やかな電気の刺激が始まった3秒後に、正常に動き回ることができた。治療はL-ドーパと併用で効果的であり、(薬剤単独では5回必要なところ)わずか2回分で有効であった。
 ドーパミンが無い小さな部位のように脳のどこで起きるかよりも、ニューロンの大きい回路の動的な点火パターンの中で、いつ事が起こるかに研究は集中している。これらの回路は同調して発振し、正常脳機能を動かしている。
 Dr. Nicolelisによれば、パーキンソンの患者は動きをコントロールしている脳部位に異常な低周波振動を持っている。感触感覚を脳に伝える脊髄の最上階層の刺激は、自発的な運動コントロールに関係している複数の脳構造を繋いで正常な点火パターンを復元して、これらの異常な振動を混乱させることによって働くのかもしれない。
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Spinal Shocks Ease Parkinson’s in Mice
http://www.nytimes.com/2009/03/20/health/20spinal.html

By SANDRA BLAKESLEE
Published: March 19, 2009

By electrically stimulating the spinal cords of rodents, scientists have reversed some of the worst symptoms of Parkinson’s disease.

As long as a mild current flows up their spines and into their brains, the animals regain the ability to scamper around their cages, as if they were normal.

The therapy, described in Friday’s issue of the journal Science, is a potential alternative to direct stimulation, which requires risky and invasive surgery to implant electrodes deep in the brain, researchers said. Only 30 percent of severely impaired Parkinson’s patients qualify for the operation.

Spinal cord stimulation would be less invasive and inherently safer, and it would reduce the amount of drugs needed to treat the disease, said the report’s lead author, Dr. Miguel A. L. Nicolelis, a neuroscientist at Duke. Dr. Nicolelis added that the procedure was now being tested on monkeys, and “if it succeeds, human clinical trials could begin in the next few years.”

An expert on stimulation theories who was not involved in the research, Dr. Rodolfo Llinás, said the treatment “makes good sense,” but he added:

“How successfully it will translate to humans is an important issue. The human spinal cord is much more complex than the rodent counterpart, and long-term stimulation might result in nasty secondary effects.”

Dr. Llinás is chairman of neuroscience and physiology at the N.Y.U. School of Medicine.

Dr. Ali Rezai, a neurosurgeon and director of the Center for Neurological Restoration at the Cleveland Clinic, said spinal cord stimulation was “technically simple to do” and had been performed on tens of thousands of people to treat chronic pain, spasticity, stroke and other medical problems. The main side effect is a sense of vibration, like pins and needles, that never lets up.

The idea of using spinal cord stimulation to treat Parkinson’s disease, however, is entirely new, Dr. Rezai said, and he called it both “provocative” and “fascinating,” though further research was needed on how it would work in practice.

Parkinson’s disease results from a loss of cells that secrete dopamine, a brain chemical essential for normal movement. Patients develop tremors, rigid posture, impaired balance and an inability to initiate movement. In the United States, at least half a million people are believed to suffer from Parkinson’s disease, and about 50,000 new cases are reported each year.

The first line of treatment is L-dopa, a drug that restores dopamine but stops working over time. Direct brain stimulation seeks to ease symptoms by focusing on specific brain regions involved in dopamine transmission.

In the new treatment, animals whose brains were depleted of dopamine had tiny electrodes, the size of a fingernail, implanted on their spinal cords. Three seconds after a mild electrical stimulation began, they could move about normally.

The treatment was also effective when combined with L-dopa in further experiments; only two doses of L-dopa were needed to produce movement, compared with five doses when it was used by itself.

Spinal cord stimulation represents a “big conceptual change” in how to treat Parkinson’s disease, Dr. Nicolelis said. Rather than looking at where things happen in the brain, as in small regions missing dopamine, the approach focuses on when things happen, as in the dynamic firing patterns of large circuits of neurons. These circuits oscillate in harmony and underlie normal brain function.

Parkinson’s patients have abnormal low-frequency oscillations in the brain regions controlling movement, Dr. Nicolelis said. Stimulation of the topmost layer of the spinal cord, which conveys touch sensations to the brain, may work by disrupting these abnormal oscillations, restoring normal firing patterns across multiple brain structures involved in the control of voluntary movements.

Dr. Nicolelis added that more research was needed to determine whether other mechanisms might explain the therapy’s success in rodents.

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Science 20 March 2009:
Vol. 323. no. 5921, pp. 1578 - 1582
DOI: 10.1126/science.1164901

Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's Disease

Romulo Fuentes,1*{dagger} Per Petersson,1,2* William B. Siesser,3 Marc G. Caron,1,3 Miguel A. L. Nicolelis1,4,5,6,7,8

Dopamine replacement therapy is useful for treating motor symptoms in the early phase of Parkinson's disease, but it is less effective in the long term. Electrical deep-brain stimulation is a valuable complement to pharmacological treatment but involves a highly invasive surgical procedure. We found that epidural electrical stimulation of the dorsal columns in the spinal cord restores locomotion in both acute pharmacologically induced dopamine-depleted mice and in chronic 6-hydroxydopamine–lesioned rats. The functional recovery was paralleled by a disruption of aberrant low-frequency synchronous corticostriatal oscillations, leading to the emergence of neuronal activity patterns that resemble the state normally preceding spontaneous initiation of locomotion. We propose that dorsal column stimulation might become an efficient and less invasive alternative for treatment of Parkinson's disease in the future.

1 Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
2 Department of Experimental Medical Science, Neuronano Research Center, Lund University, BMC F10, 221 84 Lund, Sweden.
3 Department of Cell Biology, Duke University, Durham, NC 27710, USA.
4 Center for Neuroengineering, Duke University, Durham, NC 27710, USA.
5 Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA.
6 Department of Psychology and Neuroscience, Duke University, Durham, NC 27710, USA.
7 Edmond and Lily Safra International Institute of Neuroscience of Natal (ELS-IINN), Natal RN 59066060, Brazil.
8 Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: fuentes@neuro.duke.edu

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脊髄電気刺激によるパーキンソン病の治療 医師の一分/BIGLOBEウェブリブログ
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