根據(jù)美國埃默里大學(xué)和佛羅里達(dá)大學(xué)梅歐診所研究人員的一項(xiàng)研究,，測定血液和腦脊液中神經(jīng)損傷蛋白可反映肌萎縮側(cè)索硬化（ALS）的病情進(jìn)展,。這項(xiàng)檢測方法將有望幫助醫(yī)生和研究人員確定ALS病情迅速進(jìn)展風(fēng)險(xiǎn)最高的患者，為這些患者提供目前正在研究或處于測試階段的新治療方法,。
我們都知道,，ALS - 也被稱為盧伽雷氏病 - 是一種漸進(jìn)的神經(jīng)退行性疾病，是由于控制隨意肌運(yùn)動(dòng)的運(yùn)動(dòng)神經(jīng)元功能惡化所致,。佛羅里達(dá)州-梅歐診所ALS診所醫(yī)療主任Kevin Boylan博士說,，ALS患者病情進(jìn)展的速度差異很大，明確診斷后的生存期從數(shù)月至10年或更長時(shí)間不等,。
該項(xiàng)研究的首席研究員Boylan博士說,，“在治療ALS患者時(shí)，我們需要更可靠的方法以確定疾病進(jìn)展速度,。許多ALS的研究人員嘗試尋找神經(jīng)損傷的分子生物標(biāo)志物檢測方法,，讓我們備受鼓舞的是本研究的結(jié)果頗具應(yīng)用前景。因?yàn)椴杉簶颖颈炔杉X脊液更容易,，我們下一步特別感興趣的是對(duì)這一方法檢測腦脊液和外周血標(biāo)本的差異進(jìn)行比較,。
研究所測定的是血液和腦脊液中重鏈神經(jīng)絲蛋白（NF-H）。正常情況下,，這些蛋白質(zhì)維持運(yùn)動(dòng)神經(jīng)元的結(jié)構(gòu),。而當(dāng)發(fā)生疾病導(dǎo)致神經(jīng)受損時(shí)，蛋白質(zhì)分解并游離進(jìn)入血清和腦脊液中,。這方面的前期研究由佛羅里達(dá)大學(xué)神經(jīng)科學(xué)家Gerry Shaw博士進(jìn)行,，他也是這項(xiàng)研究的資深研究者，同時(shí)也建立了本研究神經(jīng)絲蛋白測定方法,。
研究人員測定了梅歐診所和埃默里大學(xué)ALS患者血液和腦脊液樣本中的重鏈神經(jīng)絲蛋白水平,，發(fā)現(xiàn)該蛋白水平與病情進(jìn)展速度相關(guān)。Boylan博士說,，“我們證實(shí)該蛋白水平較高與肌無力進(jìn)展更快顯著相關(guān),，還有證據(jù)表明重鏈神經(jīng)絲蛋白水平較高的ALS患者生存期較短。
目前尚無法治愈ALS,，也沒有能使患者顯著獲益的治療手段,，許多治療方法尚在研究之中。這樣的檢測方法有助于識(shí)別病情進(jìn)展風(fēng)險(xiǎn)高的患者,。Boylan博士說,，對(duì)于主要延緩ALS病情進(jìn)展的實(shí)驗(yàn)性治療，可能更容易在病情進(jìn)展較快的患者中發(fā)現(xiàn)治療反應(yīng),。但現(xiàn)在,，臨床研究中納入的是病情進(jìn)展速度不同的患者,，這可能很難分析藥物的療效。Boylan博士說：“如果有一種方法可以識(shí)別哪些患者病情進(jìn)展可能相對(duì)較快,，就有可能用較小樣本量的患者在更短的時(shí)間內(nèi)進(jìn)行治療性試驗(yàn),。（生物谷Bioon.com）
doi:10.1136/jnnp-2012-303768
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PMID:
Phosphorylated neurofilament heavy subunit (pNF-H) in peripheral blood and CSF as a potential prognostic biomarker in amyotrophic lateral sclerosis
Boylan KB, Glass JD, Crook JE, Yang C, Thomas CS, Desaro P, Johnston A, Overstreet K, Kelly C, Polak M, Shaw G.
BACKGROUND: The phosphorylated neurofilament heavy subunit (pNF-H), a major structural component of motor axons, is a promising putative biomarker in amyotrophic lateral sclerosis (ALS) but has been studied mainly in CSF. We examined pNF-H concentrations in plasma, serum and CSF as a potential biomarker for disease progression and survival in ALS. METHODOLOGY: We measured pNF-H concentration by monoclonal sandwich ELISA in plasma (n=43), serum and CSF (n=20) in ALS patients collected at the Mayo Clinic Florida and Emory University. We included plasma from an ALS cohort (n=20) from an earlier pilot study in order to evaluate baseline pNF-H levels in relation to disease progression using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), survival and anatomical region of ALS onset. RESULTS: Higher pNF-H levels in plasma, serum and CSF showed evidence of association with faster decline in ALSFRS-R. There was evidence for a relationship of higher serum and plasma pNF-H levels with shorter survival, although evidence was weaker for CSF. pNF-H concentration in plasma (n=62) may be higher in patients with bulbar onset than in patients with spinal onset. CONCLUSIONS: In ALS, increased pNF-H concentration in plasma, serum and CSF appears to be associated with faster disease progression. Factors affecting pNF-H levels or their detection in serum and plasma in relation to disease course may differ from those in CSF. Data raising the possibility that site of ALS onset (bulbar vs spinal) may influence pNF-H levels in peripheral blood seems noteworthy but requires confirmation. These data support further study of pNF-H in CSF, serum and plasma as a potential ALS biomarker.
