Application of recombinant human insulin-like growth factor 1 (rhIGF1) in preparation of medicines for treating fragile X syndrome

A syndrome, IGFR1-AKT-S6K technology, applied in the field of medicine, can solve the problems of mouse projection neuron cell body volume, dendritic length, dendritic branching and synaptic density abnormalities, brain volume reduction and other problems

Inactive Publication Date: 2018-06-22
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have shown that IGF1-deficient mice have significant abnormalities in projection neuron cell body volume, dendrite length, dendritic branches, and synapse density, which may lead to a reduction in brain volume

Method used

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  • Application of recombinant human insulin-like growth factor 1 (rhIGF1) in preparation of medicines for treating fragile X syndrome
  • Application of recombinant human insulin-like growth factor 1 (rhIGF1) in preparation of medicines for treating fragile X syndrome
  • Application of recombinant human insulin-like growth factor 1 (rhIGF1) in preparation of medicines for treating fragile X syndrome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: The effect of long-term rhIGF1 treatment on the level of IGF1 in serum and hippocampus of FMR1KO mice

[0035] The present invention first detected the level of IGF1 in the hippocampus of the mouse serum and the key nucleus of learning and memory in the brain at 28 days (P28) and 56 days (P56) after birth, and whether long-term exogenous intraperitoneal injection of rhIGF1 (0.25 mg / kg) can Regulate the level of IGF1 in mouse serum and hippocampus. Take mice of the same age and different treatment groups at 28 and 56 days after birth. On the same day, before the injection of rhIGF1, 2h and 24h after the injection, blood was taken from the heart after anesthesia, left for 30min, centrifuged at 2000 rpm for 5min, and the serum was taken and frozen at -80℃. Check. After the mice were sacrificed, their brains were quickly decapitated, and the hippocampus was quickly separated and weighed separately. The lysate was added according to the tissue weight (mg): volume of...

Embodiment 2

[0037] Example 2: Effect of long-term rhIGF1 treatment on the morphology of hippocampal neurons in FMR1KO mice

[0038] A large amount of evidence proves that the density of immature dendritic spine of hippocampal pyramidal neurons in FMR1KO mice is significantly increased. In the present invention, 5 mice of the same age are taken from each group, directly killed and washed with water. According to the instructions of the Golgi staining kit, 3 neurons are randomly selected, a total of 15 neurons, and dendrites of various levels within 100 μm from the cell body are selected. The number of total dendritic spines and thin dendritic spines with immature long necks and small heads on the 50μm dendrites were recorded using ImageJ software every 10μm.

[0039] See the result figure 2 ,by figure 2 According to the results in, at 56 days of birth (P56), the density of slender dendritic spine neurons in the hippocampal dentate gyrus of the KO+Vehicle group was significantly greater than t...

Embodiment 3

[0040] Example 3: Effect of long-term rhIGF1 treatment on anxiety-like behavior in FMR1KO mice

[0041] A large amount of evidence shows that FMR1KO mice exhibit obvious anxiety-like behaviors, as well as hyperactivity symptoms. The present invention uses the internationally recognized classic open field test (Open field test, OFT) elevated plus maze (Elevated plus-maze test, EPM) to detect anxiety-like behaviors in mice, and mainly uses mice to open the central area of ​​the open field and the elevated plus maze. The nervousness of the conflict between the fear of the arm area and the desire to explore novelty is used to judge the anxiety of the mice. The more anxious the mice, the shorter the residence time in the central area of ​​the open field and the open arm area of ​​the Gaojia plus maze. At the same time, the stronger the mouse's exercise activity, the longer the movement distance in the two experimental devices, and the more times the arm moves.

[0042] The open field e...

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Abstract

The invention discloses application of recombinant human insulin-like growth factor 1 (rhIGF1) in preparation of medicines for treating fragile X syndrome. The research of the invention fully proves that the level of insulin-like growth factor 1 (IGF1) in serum and brain hippocampus of a postnatal mouse with the fragile X syndrome is significantly lower than that of normal mice of the same age, and the intraperitoneal injection of the rhIGF1 can improve the level of the IGF1 of the mouse with the fragile X syndrome and further enables the level of the IGF1 to be similar to that of normal miceof the same age. The rhIGF1 has a good therapeutic effect on the core symptoms, such as hippocampal neuronal dysplasia, learning memory deficit, impaired social interaction, anxiety and giant testicular disease, of the fragile X syndrome; the effect is related to regulation on excessive activation of an IGFR1-AKT-S6K signaling pathway. The rhIGF1 is successfully used in the treatment of Rett syndrome and insulin resistance in clinical practice, has good safety, and has the advantages of being sufficient in research basis and short in possible research period compared with other therapeutic drugs under development.

Description

Technical field [0001] The invention belongs to the technical field of medicine, and is specifically the application of rhIGF1 in preparing medicines for treating fragile X syndrome. Background technique [0002] Fragile X syndrome (Fragile X syndrome, FXS) is a common X-chromosome-linked, single-gene genetic disorder of intellectual development. The incidence rate of males is about 1 / 5000, which brings a heavy burden to patients' families and society. Its main clinical manifestations are moderate to severe mental retardation, often accompanied by autism spectrum disorders (ASDs), anxiety disorders, epilepsy, etc. It also manifests as megarchidism in men. Studies believe that its main cause is due to the excessive amplification of the trinucleotide CGG at the 5'end of the untranslated region of the Fragile X mental retardation gene (FMR1), which leads to its methylation, which causes the Fragile X mental retardation it encodes. Fragile Xmental retardation protein (FMRP) is missi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/30A61P25/00A61P25/22A61P15/08
CPCA61K38/30
Inventor 冯斌王晓娟招明高成黎霏
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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