The proper functioning of the human brain depends on a very strict balance of chemicals, and in cases when it is disturbed, it may cause excessive stimulation, neurological disorders, irreparable damages, and excitotoxicity. Neurological disorders are the most rapidly expanding areas of the global healthcare sector, and excitotoxicity is one of the major impediments to the healing of patients with stroke, dementia, or brain damage.
Through R&D and expedited clinical trials, novel therapeutic approaches and emerging excitotoxicity targeting therapies are paving new frontiers and are a major area of growth in the neuroprotection market.
Neurological diseases are responsible for ~14% deaths globally due to the excitotoxicity mechanism, which leads to strokes, Alzheimer’s, and other brain injuries. But the question is how and why? Let’s search for answers to these questions below.
(Source: WHO)
What is Excitotoxicity and Why Does It Matter?
Excitotoxicity is a pathological mechanism caused by hyperstimulation of glutamate receptors, causing excess release of calcium ions, which causes nerve tissue damage, enzymatic destruction, mitochondrial malfunction, and cellular death. This leads to brain damage, stroke, and neurological conditions.
The major causes of excitotoxicity are ischemia, neuroinflammation, brain injuries, and oxidative stress. Other triggers can be reduced blood flow and metabolic imbalances. Death of neurons, synaptic dysfunction, memory loss, cognitive declines, and motor functioning impairment are the impacts of excitotoxicity.
The disorders associated with excitotoxicity are Alzheimer’s, Parkinson's, strokes, epilepsy, brain ischemia & seizures, and Amyotrophic lateral sclerosis.
Limitations of Traditional Neuroprotection Treatments
The conventional neuroprotective treatments are focused on the prevention of neural structure functioning and further injury. But these traditional approaches have high relapse and progression rates with limited effectiveness in preventing neuron.
The traditional approaches are restricted to the antagonist, channel blockers, anti-inflammatory drugs, and antioxidant therapies. Also, these methods have a low success rate.
Emerging Excitotoxicity Therapies
The emerging therapies targeting excitotoxicity are glutamate receptor modulators, gene therapy approaches, stem-cell-based treatment, RNA-based therapies, and precision medicine strategies.
NMDA receptor modulation therapy involves the regulation of NMDA receptors through ligands, ions, and neurotransmitters. In this therapy, selective antagonists curb excitotoxic signals without disrupting normal communication. Another receptor therapy involves glutamate clearance, boosting glutamate transporters such as GLT-1/EAAT2 which reduces the extracellular glutamate and prevents excitotoxic cascades.