The Electrophysiology of Motor Neuron Diseases
The Electrophysiology of Motor Neuron Diseases
批准号:
6335750
负责人:
Mark B. Bromberg
金额:
$14.5万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-08-01 至 2003-07-31
关键词:
amyotrophic lateral sclerosis child (0-11) clinical research computer program /software computer system design /evaluation data collection methodology /evaluation degenerative motor system disease electromyography electrophysiology genotype human subject infant human (0-1 year) innervation longitudinal human study method development motor neurons muscle strength neurogenetics phenotype polymerase chain reaction progressive spinal muscular atrophy technology /technique development
中文摘要
描述(由申请人提供):
脊髓性肌萎缩症(SMA)和肌萎缩侧索硬化症(ALS)
病因不明的神经退行性疾病。他们有共同的死亡
下运动神经元(LMN)导致肌肉无力,这两种疾病都是
致命的。SMA和ALS的LMN死亡机制不同。在SMA,LMN死亡可能
在有限的一段时间内发生。没有人回答是迟到了还是
持续的LMN损失。最近对SMA的遗传学研究表明,
运动神经元存活基因(SMN2)拷贝数与SMA类型之间的关系。无人应答
是拷贝数和LMN数之间的关系。在肌萎缩侧索硬化症中,
LMN死亡的机制解释了已知的特征和一系列事件
最终有可能导致LMN死亡。在肌萎缩侧索硬化症中没有回答是很自然的
LMN丢失从肌肉到肌肉的进展模式。虽然肌肉
虚弱是LMN丢失的临床表现,对于这两种疾病,
强度损失的大小并不能准确反映LMN的损失率。这个
差异是由于失神经再支配的代偿作用。
从幸存的运动神经末梢发芽的侧枝纤维。同样,
常规电生理检查不能准确测量LMN的损失。无人应答
对于这两种疾病来说,是代偿过程的动态决定了
临床状态和功能水平。
运动单位数估计(MUNE)是一种特殊的电生理测试
可以直接评估支配肌肉的LMN的数量。没有数据
关于SMA的LMN丢失的自然过程,ALS的数据很少。我们建议
为了开发和完善MUNE和其他电生理学技术来研究,
并遵循LMN损失和相关的代偿性变化的过程。对于SMA,
我们将采用MUNE技术来研究婴儿和儿童。适用于较旧的SMA和
此外,我们将改进MUNE技术以优化数据收集。对于SMA,我们
LMN丢失与临床类型和SMN2拷贝数相关。我们将开始,
在两年的赠款执行系列研究中,评估是否
LMN的损失仍在持续。对于肌萎缩侧索硬化症,我们将确定并比较
远端和近端肌肉的LMN丢失模式。在较老的SMA和ALS中,
我们将评估LMN损失与抵押品衡量标准之间的关系
神经再支配和力量。我们预计穆恩和其他人
电生理学技术将直接适用于
SMA和ALS的临床试验,因为这些技术可以用作
提供信息的终点措施。促进MUNE在临床上的应用
试验中,我们将开发和改进这些技术,使其可用于
任何参与试验的临床中心。目前,大多数MUNE技术
依靠专有软件。我们将开发基于PC的软件
计算机系统,使其可供所有实验室使用。
英文摘要
DESCRIPTION (provided by applicant):
Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are
neurodegenerative disorders of unknown etiology. They have in common death of
lower motor neurons (LMN) causing muscle weakness, and both disorders are
fatal. Mechanisms of LMN death differ for SMA and ALS. In SMA, LMN death may
occur over a limited period of time. Unanswered is whether there is late or
continued LMN loss. Recent genetic studies in SMA indicate a relationship
between survival motor neuron gene (SMN2) copy number and SMA type. Unanswered
is the relationship between copy number and LMN number. In ALS, no single
mechanism of LMN death explains known features, and a cascade of events
ultimately leading to LMN death is likely. Unanswered in ALS is the natural
pattern of progression of LMN loss from muscle to muscle. Although muscle
weakness is the clinical manifestation of LMN loss for both disorders, the rate
of loss of strength does not accurately reflect the rate of loss of LMNs. The
discrepancy is due to the compensatory effects of reinnervation of denervated
fibers by collateral sprouting from surviving motor nerve terminals. Similarly,
routine electrophysiologic tests do not accurately measure LMN loss. Unanswered
for both disorders is the dynamics of the compensatory process that determines
the clinical state and level of function.
Motor unit number estimation (MUNE) is a special electrophysiologic test that
can directly assess the number of LMNs innervating a muscle. There are no data
on the natural course of LMN loss for SMA, and little data for ALS. We propose
to develop and refine MUNE and other electrophysiologic techniques to study,
and follow the course of LMN loss and associated compensatory changes. For SMA,
we will adapt MUNE techniques to study infants and children. For older SMA and
ALS, we will refine MUNE techniques to optimize data collection. For SMA, we
will correlate LMN loss with clinical type and SMN2 copy number. We will begin,
in the two years of the grant-performing serial studies, to assess whether
there is continued LMN loss. For ALS, we will determine and compare the rate
and pattern of LMN loss in distal and proximal muscles. In older SMA and ALS,
we will assess relationships between LMN loss and measures of collateral
reinnervation and strength. We anticipate that MUNE and other
electrophysiologic techniques will have direct applicability to the design of
clinical trials for SMA and ALS, because these techniques can be used as
informative end-point measures. To facilitate the use of MUNE in clinical
trials, we will develop and refine the techniques in a form that can be used in
any clinical center participating in trials. Currently, most MUNE techniques
rely on proprietary software. We will develop software for use on PC-based
computer systems, making them available to all laboratories.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
CLINICAL TRIAL: EARLY TREATMENT OF ALS WITH NUTRITION AND NIPPV
-
批准号:7718508
-
项目类别:
-
资助金额:$0.34万
-
财政年份:2008
-
负责人:Mark B. Bromberg
-
依托单位:
EARLY TREATMENT OF ALS WITH NUTRITION AND NIPPV
-
批准号:7604966
-
项目类别:
-
资助金额:$2.19万
-
财政年份:2007
-
负责人:Mark B. Bromberg
-
依托单位:
EARLY TREATMENT OF ALS WITH NUTRITION AND NIPPV
-
批准号:7376476
-
项目类别:
-
资助金额:$1.34万
-
财政年份:2006
-
负责人:Mark B. Bromberg
-
依托单位:
MINOCYCLINE IN 400 SUBJECTS WITH ALS
-
批准号:7376455
-
项目类别:
-
资助金额:$0.93万
-
财政年份:2006
-
负责人:Mark B. Bromberg
-
依托单位:
MINOCYCLINE IN 400 SUBJECTS WITH ALS
-
批准号:7201440
-
项目类别:
-
资助金额:$0.67万
-
财政年份:2005
-
负责人:Mark B. Bromberg
-
依托单位:
The Electrophysiology of Motor Neuron Diseases
-
批准号:6529714
-
项目类别:
-
资助金额:$13.85万
-
财政年份:2001
-
负责人:Mark B. Bromberg
-
依托单位:
COMPARISON OF THE RESPONSE TO THERAPY WITH GAMMAR IV OR PLACEBO
-
批准号:6114845
-
项目类别:
-
资助金额:$2.81万
-
财政年份:1998
-
负责人:Mark B. Bromberg
-
依托单位:
COMPARISON OF THE RESPONSE TO THERAPY WITH GAMMAR IV OR PLACEBO
-
批准号:6276080
-
项目类别:
-
资助金额:$2.66万
-
财政年份:1997
-
负责人:Mark B. Bromberg
-
依托单位: