Neurochlore: understanding and treating developmental brain disorders
In 2011, the discovery of the potential beneficial action of Bumetanide, a diuretic, on autism symptoms led us, Eric Lemonnier, Nouchine Hadjikhani and I, to found Neurochlore, a young Start-Up hosted at Inmed. This Start-Up is leading clinical trials necessary to obtain marketing authorization for Bumetanide for the treatment of autism. Neurochlore is dedicated to both drug development and basic research to understand the molecular mechanisms of autism and the mechanisms of action of Bumetanide.
B&A Therapeutics: understanding and treating Parkinson’s disease
Parkinson’s disease (PD) is caused by the degeneration of dopaminergic neurons of the substantia nigra that innervate the striatum. The drug treatment of PD is based essentially on the compensation of the lack of dopamine by the administration of a dopamine precursor, L-dopa. Still, this approach has its limits including a progressive loss of efficiency and dyskinesias that occur every few years. It is therefore essential to find new therapeutic approaches not based on the dopaminergic system and to this end determine the effects of the lack of dopamine in striatal neurons. In a recent study, we found that the main population of neurons in the striatum, the medium-sized spiny neurons (MSNs), which constitute 95% of striatal neurons, generate giant GABAergic activities in two mouse models of PD. These currents are a signature of the disease as L-Dopa as the lesion of the subthalamic nucleus in humans attenuate disease also eliminate these currents. Therefore, drugs that block these giant currents might provide a new therapeutic approach.
Who generates these activities? Our experimental work suggests that these activities are due to an excessive increase of chloride in striatal neuronal populations. This increase results in excitability of neurons that generate the giant currents. So the question is how to lower the chloride level? But it turns out that the diurétique- Bumétanide- known for its action on a major chloride input mechanisms in the kidney cells as in neurons completely block these giant currents (unpublished results). So, we undertook a pilot clinical trial of 4 PD patients with Professor P. Damier (Nantes) and obtained promising results (in progress).
With these observations, we created B&A Therapeutics with researchers and clinical experts of the understanding and treatment of Parkinson’s disease to understand the regulation of intracellular chloride and their effects on GABAergic signals, identify the neurons that generate these giant currents and undertake clinical trials to bring to market new agents to mitigate Parkinson’s disease.