利魯唑組比值治療前后比較課件

1、ALS關(guān)鍵時(shí)期的關(guān)鍵治療復(fù)旦大學(xué)華山醫(yī)院蔣雨平Ravitts等100例有上、下運(yùn)動(dòng)神經(jīng)元病所致的ALS分析平均年齡62歲（2685歲）。男性58%，女性42%。92%散發(fā)性，8%為家族性。診斷前癥狀時(shí)間平均為11月（336月）延髓發(fā)病為29%。單上肢34%（右24%，左10%）。軀干占6%。單下肢29%（右13%，左15%）。雙側(cè)肢體占1%。不能分型者占2%。延髓和上肢病情進(jìn)展比軀干和下肢快，惡化嚴(yán)重。288例ALS各亞型存活時(shí)間（Tomik等2006)單上肢型單下肢型進(jìn)行性延髓麻痹單肢型偏側(cè)型比率10%90%男/女5.3/13.6/11.5/1平均病程(月)74.253.142.158.2就

2、診后平均存活(月)34.22928.743.7關(guān)鍵時(shí)期診斷的要點(diǎn)-找到肯定的運(yùn)動(dòng)神經(jīng)元損害的依據(jù)及早找到“治療窗”216/301試驗(yàn)的綜合分析，降低風(fēng)險(xiǎn)35%。最新研究數(shù)據(jù)，降低風(fēng)險(xiǎn)67%。利魯唑組（n=17）CTX組（n=7）治療前治療后治療前治療后NAA/Cr1.850.161.930.16*1.940.171.920.16Cho/Cr1.030.111.020.101.060.091.090.15利魯唑組和CTX組1H-MRS檢查隨訪結(jié)果（NAA/Cr和Cho/Cr比值以XS表示）*利魯唑組NAA/Cr比值治療前后比較:P0.05,有統(tǒng)計(jì)學(xué)差異.利魯唑組CTX組治療前治療后治療前治療后A

3、LS-FRS評(píng)分33.536.1033.706.4032.438.0232.297.89Appel評(píng)分44.9417.5932.438.0248.4320.1149.0020.26利魯唑和CTX治療ALS病的兩組臨床評(píng)分比較兩組治療前后比P0.05.在利魯唑組和Appel量表-延髓部分評(píng)分隨訪由治療前的9.055.29改善至8.234.29,P0.05。利魯唑組（n=10）免疫治療組（n=7）治療前治療后治療前治療后血漿谷氨酸濃度251.3554.37205.7455.33*261.8950.01228.0748.63不同治療組對(duì)血漿谷氨酸濃度的影響 （濃度單位為molL-1)*利魯唑組治療前

4、后血漿谷氨酸濃度下降,P5yrsEldepryl inhibitor, USAAcetylcysteine24 N-=110 Death, Antioxidant negative The Netherlands 50mg/kg/day sc tracheostomy Follow-up 12 months CoenzymeQ10105N=185ALSFRSrMitochondrialcofactor,antioxidantIncludesFVC60% andSymptomonset 5yearsUSAPhase 9 months studyperiodVerapamil104 N=72 MV

5、IC and pulmonary Antioxidant negative Treatment function effect compared to USA 3 months lead- Calcium natural history lead-in in, 6 months channel period treatment, 3 blocker months post- treatment Creatine41 N:175 Death, tracheostomy Energy negative metabolism The Netherlands 16 months follow-up,

6、sequential design Creatine42 N=104 MVIC in 8 arm Energy Negative, well muscles metabolism tolerated USA 5gms PO QD 6 months follow- up Creatine105 n=156 MVIC, Energy Includes disease change in metabolism duration 5 years USA Phase III arm strength 10gms for 5 d, 5 gms thereafter study period 9 month

7、sNimodipine103 N=87 MVIC and pulmonary Antioxidant negative function USA Mitigating excitotoxicity IGF-I56 266 Appel scores neurotrophic Functional decline significantly less in USA 9 months high-dose group 0.05 or 0.1mg/kd/day sc IGF-I 57 N=183 Appel scores neurotrophic Negative result. US results

8、not confirmed.Europe 9 months Review combining both trials suggests IGF-1 :placebo modest effect43. randomization = Third trial ongoing. 2:1 0.1mg/kg/day scBDNF52 N=1135 6 months FVC neurotrophic Primary analysis negative, but benefit USA 6 months study in secondary period analyses; 25 or 100pg/kg L

9、ow event rate sc Exclusion ALSFRS18, FVC60% SR 57746A N=867 Death/tracheostomy neurotrophic negative, but non- and VC significant beneficial Xaliproden.61 18 months effect on VC for 2rug follow-up arm multinationa 1mg or 2mg QD, Excluded FVC5 yrsSR 57746A N=1210 Death/tracheostomy neurotrophic Overa

10、ll negative, but and VC trend towardsXaliproden .61 18 months beneficial effect of follow-up 1mg on VC multinational 1mg or 2rug QD, Excluded FVC5 yrs 50mg BID IGF-1105 N=330 MMT Neurotrophic Includes FVC60% agent predicted, USA Phase III progressive motor weakness onset Study period 2 years 24 mont

11、hs CNTF58 N=730 MVlC change neurotrophic Excluded ALSFRS5 yrs 15 or 30 pg/kg No benefit sc TIW Side effects include anorexia, weight loss, cough CNTF.59 N: 570 MVIC and FVC neurotrophic Excluded ALS3 yrs, change combined FVC75%predicted,USAPhase IIIDisease duration 3 years 4 months lead in, 9 months study periodThalidomid 治療ALS的二期開(kāi)放臨床試驗(yàn)動(dòng)物試驗(yàn)中應(yīng)用thalidomid 減少體內(nèi)TNF-的水平，延長(zhǎng)ALS動(dòng)物模型的生存期，是一個(gè)很好的TNF-抑制劑。ALS患者每日用thalidomid 400mg。23 ALS 僅有18人完成整個(gè)試驗(yàn)評(píng)定指標(biāo)ALS功能評(píng)分（ALSFR