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.
Another emerging therapy for preventing excitotoxicity is bioengineered therapy, where pre-conditioned mesenchymal stromal cell-derived extracellular vesicles are engineered to enhance neurorecovery, reduce excitotoxic damage, and promote tissue repair. These therapies are holistic and have a long-term effect.
Nano-based and targeted delivery systems, such as dual-targeting liposomes, improve barrier penetration and drug accumulation in injured brain regions. These smart drug delivery systems increase efficiency and reduce side effects.
Future Trends in Excitotoxicity Research
With the current progression report, in the future, we will be witnessing nanotechnology-based drug research, biomarker-driven treatments, regenerative medicines, brain-computer interface systems, and preventive neurotherapies.
AI and machine learning are accelerating the early stages of targeted drug delivery. The AI and machine learning technologies will be integrated with the healthcare systems for more precise treatments, effective clinical trials, and credible innovations and research.
(Source: Elsevier Insights)
Conclusion
Neurological disorders, which are associated with brain cell damage, affect millions of global citizens. Excitotoxicity is at the center of most of these diseases. Attack on excitotoxicity is the most significant advance in neuroprotection.
With the scientific innovation and the augmentation of neuronal demand, there is a clinical opportunity and market possibility in therapies that are viable in alleviating excitotoxic injury. Emerging therapies addressing excitotoxicity represent a shift in the care of the brain by integrating biology, engineering, and precision medicine.
FAQs
- What are the benefits of emerging excitotoxicity therapies?
- The benefits of emerging excitotoxicity therapies are improved neuron survival, slowed disease progression, enhanced quality of life, and reduced side effects from treatments.
- What are the challenges in excitotoxicity therapy?
- The challenges in excitotoxicity therapies are blood-brain barrier penetration, drug delivery issues, high research costs, and safety & ethical concerns.
- What is the role of AI in treating excitotoxicity?
- The AI can be utilized in identifying targets in nano-based and target delivery systems, predictive modeling for neuroprotection, personalized therapy development, and precision medicine delivery.
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