science
Pushing the boundaries of neuroscience drug discovery
At IAMA, we are working to unlock major breakthroughs in neuroscience drug discovery and precision medicine to develop personalized treatments for patients suffering from untreatable neurological conditions. We are advancing treatments to make an impact on individuals affected by neurological disorders and their families.
We are developing diverse classes of small molecules to selectively inhibit validated targets, including the sodium-potassium chloride cotransporter (NKCC1).
our approach
Targeting Chloride Imbalance to Restore Neuronal Inhibition
In many neurological disorders, a disruption in chloride homeostasis leads to an imbalance between excitation and inhibition in the brain. NKCC1, a cation-chloride cotransporter, contributes to this imbalance by driving chloride influx into neurons, which in turn weakens GABAergic inhibition. Our approach targets this dysregulation at its core. By selectively inhibiting NKCC1, we aim to lower intracellular chloride levels and restore inhibitory tone, rebalancing neuronal excitability.
This mechanism becomes particularly relevant in conditions where intracellular chloride accumulates, disrupting the inhibitory action of GABA and tipping the balance toward excessive neuronal excitation. Such chloride imbalance is often observed during early brain development, but also in various pathological states across the lifespan. By targeting the underlying ionic dysregulation, we aim to restore proper inhibitory signaling and rebalance neural circuit activity.
a broad role across cns disorders
A shared pathophysiological mechanism across CNS disorders
NKCC1 dysregulation is a convergent mechanism underlying multiple central nervous system (CNS) disorders. When intracellular chloride accumulates, the inhibitory function of GABA is compromised, leading to neural circuit hyperexcitability, neuroinflammation, and altered synaptic plasticity. This dysregulation has been identified across several major therapeutic areas, including:
- Epilepsies and seizure-related disorders (e.g., refractory epilepsy, status epilepticus)
- Neurodevelopmental disorders (e.g., autism spectrum disorder, Rett and Dravet syndromes)
- Psychiatric disorders (e.g., schizophrenia, bipolar disorder, anxiety)
- Pain disorders (e.g., neuropathic pain, inflammatory pain)
- Neurotraumatic conditions (e.g., spinal cord injury, post-injury trauma, paralysis)
- Neurodegenerative diseases (e.g., Alzheimer’s, ALS, Huntington’s)
