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Composition for preventing and treating amyotrophic lateral sclerosis

A technique for lateral sclerosis and compositions, applied in the fields of relieving or treating mammalian amyotrophic lateral sclerosis, preparation prevention, homocysteine ​​down-regulator, capable of solving specific and effective treatment methods, lack of amyotrophic lateral sclerosis Cable hardening and other issues

Inactive Publication Date: 2010-03-24
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Because the etiology and pathogenesis of amyotrophic lateral sclerosis are still unclear, so far, there is still a lack of specific and effective treatment methods for amyotrophic lateral sclerosis in this field

Method used

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  • Composition for preventing and treating amyotrophic lateral sclerosis
  • Composition for preventing and treating amyotrophic lateral sclerosis
  • Composition for preventing and treating amyotrophic lateral sclerosis

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0089] A. Sample Preparation

[0090] 1. Sample preparation: Accurately draw 50 μl of plasma sample into a 1.5ml centrifuge tube, add 50 μl of internal standard solution (DL-homocystine-D8) and 50 μl of reducing agent (1,4-dithiothreitol), and mix uniform. Leave at room temperature for 30 minutes, add 50 μl of protein precipitant (trichloroacetic acid), vortex and mix for 30 seconds, centrifuge at 15,000 rpm for 3 minutes at high speed, and absorb the supernatant for chromatographic analysis.

[0091] 2. Standard product preparation: Accurately draw 5 μl of control solution (DL-homocysteine), add 45 μl of diluent (calf serum aqueous solution) to dilute, and process in the same way as the plasma sample, and the obtained supernatant is used for chromatographic analysis Used.

[0092] B. Liquid chromatography-tandem mass spectrometry analysis (LC-MS / MS analysis)

[0093] 1. Chromatographic conditions: the chromatographic column is filled with octadecylsilane bonded silica gel;...

Embodiment 1

[0112] Example 1. The combination of folic acid or folic acid and vitamin B12 delays the onset time of SOD1-G93A model mice and prolongs the lifespan of mice

[0113] The onset symptoms of SOD1-G93A transgenic mice are very similar to the clinical manifestations of ALS patients, showing progressive muscle weakness, muscle atrophy, until paralysis and death, and the pathological sign is selective degeneration of motor neurons.

[0114] In the embodiment, the inventors used the Rotarod instrument to detect the exercise ability of mice, which was used as an indicator for evaluating the occurrence and development of diseases. Through observation, it was found that the average onset time of the mice in the FA-SOD1 group administered with folic acid was delayed by 7 days compared with the mice in the SOD1 group administered with normal saline (114.4±1.7 days (FA-SOD1) vs 107.9±1.8 days (SOD1) , x 2 =6.33, P2 =8.989, P2 =0.015, P>0.05), see figure 1 a.

[0115] The present invento...

Embodiment 2

[0116] Example 2. Combination of folic acid or folic acid and vitamin B12 reduces plasma homocysteine ​​levels in mice

[0117] In view of the damage effect of homocysteine ​​on nerve cells, and may cause neurodegeneration in SOD1-G93A mice, the Hcy levels in the plasma of model mice and wild-type mice in each group were measured to quantify the significant changes. Particularly important.

[0118] According to the results of LC-MS / MS, the inventors saw that there was a significant difference (6.84±0.4 μmol / L (SOD1) vs 3.8 μmol / L (SOD1) vs 3.8 ±0.26μmol / L (WT), P0.05), see figure 2 .

[0119] The results showed that the plasma Hcy level of SOD1-G93A model mice was significantly higher than that of wild-type mice, and folic acid or the combination of folic acid and vitamin B12 could significantly reduce the plasma Hcy level of model mice.

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Abstract

The invention relates to a composition for preventing and treating amyotrophic lateral sclerosis. The invention discloses a use of homocysteine downregulator in the preparation of a composition for preventing, alleviating or treating the amyotrophic lateral sclerosis of mammal, wherein the downregulator is a folic acid or a mixture of the folic acid and a vitamin B12. The downregulator can effectively alleviate the amyotrophic lateral sclerosis of mammal, reduce the level of inflammatory factors in the spinal cord of mammal, reduce the level of apoptosis protein in the spinal cord, and improvethe level of anti-apoptotic protein in the spinal cord.

Description

technical field [0001] The invention belongs to the field of biotechnology, and more specifically, the invention relates to the use of a homocysteine ​​down-regulator in the preparation of a composition for preventing, alleviating or treating amyotrophic lateral sclerosis in mammals. Background technique [0002] Amyotrophic lateral sclerosis (ALS) is a disease that results in the selective death of motor neurons, and about 20% of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the copper / zinc superoxide dismutase (SOD1) gene related. Model mice overexpressing the mutant SOD1 gene exhibit clinical manifestations similar to patients with amyotrophic lateral sclerosis, and are therefore widely used in clinical and basic research on the disease. [0003] Amyotrophic lateral sclerosis is a fatal neurodegenerative disease, its etiology and pathogenesis are still unclear, current studies have confirmed that glutamate excitatory amino acid toxicity, ...

Claims

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Application Information

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IPC IPC(8): A61K31/519A61K31/714A61P25/02A61P37/06
Inventor 乐卫东张晓洁陈晟李靓王倩
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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