Alcobra Says MG01CI No Effect on Dopamine/Noradrenaline Targets
Alcobra Ltd. (Nasdaq: ADHD) (the "Company"), an emerging biopharmaceutical company primarily focused on the development and commercialization of its proprietary drug, MG01CI (Metadoxine extended-release), to treat cognitive dysfunctions, such as ADHD and Fragile X Syndrome, announced today the results from a series of preclinical studies that evaluated the mechanism of action of MG01CI. MG01CI is composed of a dual-release formulation of Metadoxine that provides immediate as well as extended-release formulations in a single oral dose.
"These studies shed important light on the novel mechanism of action and the unique effects that MG01CI may have in treating cognitive dysfunctions," commented Dr. Yaron Daniely, President and CEO of Alcobra Ltd. "MG01CI appears to enhance the ability of cells to correct abnormal signaling pathways that may be involved with cognitive impairment, while not increasing levels of neurotransmitters in the brain such as dopamine, norepinephrine and serotonin. We believe these findings might account for the improved effect on attention as well as the favorable tolerability profile that we have observed thus far in clinical trials with MG01CI."
The studies showed that Metadoxine is a selective antagonist to the 5-HT2B receptor, a member of the serotonin receptor family. Importantly, Metadoxine did not show any binding to other serotonin receptors, and did not bind the characterized targets of existing stimulant and non-stimulant medications (dopamine and norepinephrine receptors and transporters). In accordance with these findings, Metadoxine did not affect the concentration of these neurotransmitters or their metabolites in the brain.
Metadoxine treatment affected several specific molecular targets residing inside the cell in a dose-dependent manner, including critical signaling modulators such as the proteins Akt and Extracellular signal-related Kinase (ERK), but did not affect other targets such as cyclic AMP (cAMP) and Protein Kinase A (PKA). In a preclinical Fragile X disease model, elevated levels of Akt and ERK were normalized (reduced) by Metadoxine, while levels of the GST protein were increased. Electrophysiological studies also showed that Metadoxine caused a dose-dependent, reversible reduction in glutamatergic excitatory transmission and enhancement of GABAergic inhibitory transmission, changes that may be associated with cognitive regulation.
"Our findings to date suggest a distinct mechanism of action for Metadoxine in treating cognitive disorders such as ADHD and Fragile X Syndrome," added Dr. Jonathan Rubin, Chief Medical Officer of Alcobra Ltd. "We are eager to move forward with additional clinical trials in these populations as we learn more about the differentiated characteristics of our product."
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