Methods Of Treating Fragile X Syndrome And Related Disorders
a fragile x syndrome and related disorder technology, applied in the field of methods of treating or alleviating a symptom of fragile x syndrome and related disorders, can solve the problems of memory loss, anxiety, and deficits of executive function, and young children with fragile x syndrome often have delays in developmental milestones
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example 1
Metadoxine in Fragile X Syndrome
[0106]Mice were injected once daily for one week prior and during behavioural testing. All mice were intraperitonealy injected with 150 mg / kg / day of Metadoxine (referred as M in the figures) and vehicle (referred as V in the figures).
[0107]The experiments presented herein demonstrate that Metadoxine significantly improved memory and learning during the contextual fear paradigm. A significant improvement in memory was also detected in the fmr1 KO mice treated with Metadoxine in several different tests such as Y-maze and T-maze showing significant improvement in cognitive functions. Metadoxine treatment also showed positive effect in some of the social interaction paradigms.
[0108]1A. Contextual Fear Conditioning: Test of Memory and Learning
[0109]Contextual fear conditioning is the most basic of the conditioning procedures. It involves taking an animal and placing it in a novel environment, providing an aversive stimulus, and then removing it. When the a...
example 2
Biochemical Effect of Metadoxine Treatment on FXS-Associated Biomarkers
[0140]After treatment with Metadoxine (150 mg / kg), the brain tissues of WT-V, WT-M, KO-M and KO-M mice were harvested and analyzed for biomarkers reflecting neuronal signaling pathways known to be involved in the pathophysiology of Fragile X syndrome. Specifically, FXS neuronal phenotype is thought to be mediated via induction of RAS-MEK-ERK and PI3K-Akt-mToR pathways. Reduced cAMP induction and PKA signaling have been also linked to FXS.
[0141]The activation of ERK1 / 2 and AKT, as indexed by phosphorylated ERK1 / 2 (pERK1 / 2) and phosphorylated AKT (pAKT), respectively, were increased in KO-V mice as compared to WT-V, while increased pERK and pAKT levels were normalized in KO-M (150 mg / kg) mice, as indicated by a significant reduction of pERK and pAKT levels as compared to KO-V (p<0.01 and p<0.05, respectively). However, we did not see any improvement in cAMP levels nor PKA activity in KO-M mice as compared to KO-V. ...
example 3
Effect of Metadoxine Treatment on Oxidative Stress
[0142]There is a growing body of evidence that oxidative stress and subsequently oxidant-mediated neuronal damage play a role in the pathophysiology of FXS. We therefore examined the effect of Metadoxine on a key component in oxidative stress, the anti-oxidant Glutathione S-Transferase (GST) protein levels in WT-V, WT-M, KO-V and KO-M animals.
[0143]The data shows a decrease in GST protein levels in KO-V mice as compared to WT-V group, while KO-M mice exhibited significant increased GST levels (p<0.01) when compared to KO-V mice, indicating that treatment of KO mice with Metadoxine (150 mg / kg) reduces the oxidative damage induced in KO-V mice. (FIG. 9)
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