Advancements in Dipraglurant Research for Post-stroke Recovery by Addex Supported by Findings in Brain Journal
Monday, September 04, 2023
Addex Therapeutics (SIX and Nasdaq: ADXN), a clinical-stage pharmaceutical company specializing in allosteric modulation-based drug discovery and development, has disclosed new findings published in the journal Brain. These results shed light on the potential therapeutic benefits of mGlu5 receptor negative allosteric modulators (NAMs) in aiding the recovery of neurological function after a stroke. This breakthrough suggests the possibility of advancing dipraglurant as a potential treatment for post-stroke recovery. Dipraglurant, an innovative orally-administered compound with high selectivity for the mGlu5 receptor, is now poised for Phase 2 clinical trials following successful preclinical evaluations in models of post-stroke recovery.
Mikhail Kalinichev, PhD, Head of Translational Science at Addex, commented on this milestone, stating, "The role of the mGlu5 receptor in various neurological conditions and its influence on brain plasticity have been extensively studied. Nevertheless, this marks the first instance where inhibition of this particular receptor subtype has been linked to the enhancement of post-stroke functional recovery. We are highly encouraged by the researchers' specific exploration of mGlu5 NAMs, highlighting the significant potential of this approach in facilitating the neural network recovery crucial for patients to regain lost functions."
The process of functional recovery following a stroke relies heavily on the establishment of new neural connections or the reactivation of existing ones. A growing body of evidence suggests that the mGlu5 receptor plays a pivotal role in modulating brain plasticity and function. Researchers conducted a comprehensive investigation into the impact of mGlu5 inhibition on network reorganization and functional recovery in preclinical stroke models. The published study, titled "Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity," revealed compelling results. Daily administration of mGlu5 NAMs for a 12-day period, beginning either 2 or 10 days post-stroke, led to the restoration of lost somatosensory functions without affecting infarct size. Notably, signs of somatosensory recovery, as reflected in the improved use of affected limbs, became apparent within hours of treatment initiation and continued to progress over the subsequent 12 days. Activation of mGlu5 with a positive allosteric modulator thwarted functional recovery, while it was accelerated in mice with mGlu5 knocked out. Additionally, optical intrinsic signal imaging showed that mGlu5 inhibition reversed widespread disruptions in resting-state functional connectivity in sensorimotor cortices contralateral to the lesion and bilaterally in visual cortices.
Tim Dyer, CEO of Addex, emphasized the significance of these findings, stating, "This groundbreaking research solidifies our strategic decision to explore the potential of dipraglurant in post-stroke recovery. There is an immense unmet medical need for novel therapies to aid stroke patients in their recovery journey, with no approved drugs currently available to promote functional recovery. Based on its oral availability, safety profile, and selectivity for the mGlu5 receptor, we believe dipraglurant is a promising candidate for future development in post-stroke recovery."
