Angela Ruban, Faculty of Medicine, Sagol Neuroscience, Tel Aviv University, Tel Aviv, Israel

Glutamate-regulatory enzymes as an emergency neuroprotective treatment

Funded in: 2021, 2022, 2023


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Problem: Urgent need for novel strategies to alleviate devastating conditions of neurotrauma
Target: Reduce excess of glutamate in the central nervous system
Goal: Treatment of patients with neurotrauma in the very near future

Glutamate is the most widely distributed neurotransmitter in the brain.  Numerous studies over the past decades have consistently shown that high levels of glutamate in the brain can damage and kill neurons. Recognition of this phenomenon (“excitotoxicity”) has spawned intensive research in the fields of neurotrauma and has demonstrated that high levels of extracellular glutamate in the brain results in the deaths of neurons and significant motor impairment. Reducing Central Nervous System (CNS) glutamate levels shortly after the injury will inhibit the cascade of toxic events and significantly reduce secondary damage, improve the functional recovery, and the regenerative process after spinal cord injury. However, there are currently no clinical treatments available to promote neuronal regeneration and functional recovery after SCI.

The aim of this proposed research is to evaluate the applicability and therapeutic efficacy of the first emergency neuroprotective approach to treat spinal cord injury. The neuroscientists have developed a radically different strategy to reduce excess CNS glutamate by reducing its levels in the blood circulation, which has been shown to be extremely effective in stroke, traumatic brain injury, and Paraoxon intoxication in animal models. Recently, they have demonstrated the significant neuroprotective effect of the treatment with two enzymes followed by improved motor function.

Their study will pioneer the testing of this approach. Since no side effects have been reported following initial toxicology study, the novel approach hereby proposed may be of high clinical significance for the treatment of patients with neurotrauma in the very near future.

The proposed novel treatment is of particular therapeutic relevance, because it demonstrates a strong neuroprotective effect and a safe toxicology profile. Therefore, the proposed therapeutic strategy has high feasibility to be tested in Clinical Trials shortly after completing the current study and potentially result in a smaller incomplete injury followed by better functional outcome and significantly higher quality of life in injured people.