Alcobra unveils results from preclinical studies of cognition drug
Israel-based Alcobra has released results from a series of preclinical studies that assessed the mechanism of action of its proprietary drug MG01CI (Metadoxine extended-release) for the treatment of cognitive dysfunctions, such as attention deficit hyperactivity disorder (ADHD) and Fragile X Syndrome.
The trials showed that Metadoxine is a selective antagonist to the 5-HT2B receptor, a member of the serotonin receptor family and it did not show any binding to other serotonin receptors as well as the characterised targets of the current stimulant and non-stimulant medications.
The company said that in line with the findings, Metadoxine did not affect the concentration of the neurotransmitters or their metabolites in the brain.
The treatment of metadoxine affected many specific molecular targets residing inside the cell in a dose-dependent manner, including critical signalling modulators like 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).
Alcobra president and CEO Yaron Daniely said MG01CI is expected to improve the ability of cells to correct abnormal signalling 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 favourable tolerability profile that we have observed thus far in clinical trials with MG01CI," Daniely said.
It is seen that in a preclinical Fragile X disease model, elevated levels of Akt and ERK were reduced by Metadoxine, while levels of the GST protein were increased.
According to the electrophysiological studies, Metadoxine use resulted in dose-dependent, reversible reduction in glutamatergic excitatory transmission and improvement of GABAergic inhibitory transmission, changes that may be associated with cognitive regulation.
MG01CI is a dual-release formulation of Metadoxine which offers immediate and extended-release formulations in a single oral dose.
Previously, results from a Fragile X study, funded in part by the FRAXA Research Foundation, showed significant improvement in cognitive and social functioning following treatment with Metadoxine in a valid animal model of Fragile X Syndrome.
MG01CI is being developed as a non-stimulant with a differentiated mechanism of action that targets neither dopamine nor norepinephrine. It represents a safer alternative to stimulant-based treatments and a more tolerable and effective treatment than the non-stimulants, which are currently in the market.
The company believes MG01CI to be a promising candidate for the treatment of multiple cognitive dysfunctions, which currently has no approved pharmacological treatment.