A target for peptide-based and small molecule-based therapies for treating neurological diseases

A novel cell permeable peptide targeted therapy to tackle the devastating ischemic stroke New strategy of targeting excitotoxicity without directly antagonizing NMDAR when preventing ischemic strokeIn vitro and in vivo studies with the cell permeable p…
  • A novel cell permeable peptide targeted therapy to tackle the devastating ischemic stroke
  • New strategy of targeting excitotoxicity without directly antagonizing NMDAR when preventing ischemic stroke
  • In vitro and in vivo studies with the cell permeable peptide demonstrates neuron protection against ischemic injury

Background and Unmet Need:

15 million individuals worldwide suffer from a stroke each year resulting in patient disability and mortality. The hallmark and most devastating consequence of stroke is the neuronal cell death caused by injury-induced oxidative stress. Currently, the only 2 effective therapies are thrombolysis and thrombectomy; however, these 2 approaches have significant limitations and do not protect against neuronal loss. Numerous factors are involved in neuronal damage during ischemic stroke, among which NMDAR mediated calcium overload has been the center of extensive research for understanding the underlying mechanisms and for developing effective therapeutics for ischemic stroke. However, the development of stroke-mitigating drugs by antagonizing NMDARs has only been characterized by success in animal studies but subsequent failure in a clinical trial. The lack of clinical success with excitotoxic NMDAR antagonists prompted a shift of the focus of stroke neuroprotection research towards the identification of downstream intracellular signaling pathways triggered by NMDAR. Thus, there is a significant need for a more complete therapeutic approach that is effective for all types of strokes, including that outside of the current therapeutic window and addresses both the short and long-term consequences of neuronal injury.

Technology:

UConn researchers have developed a membrane-permeable peptide that effectively protects mice against ischemic stroke injury by disrupting the interactions between TRPM2 and NMDA receptors (NMDAR) which may provide a new therapeutic strategy to tackle the devastating ischemic stroke. Dr. Lixia Yue and her team discovered that TRPM2 enhances NMDAR activation and excitotoxicity, resulting in calcium overload and subsequent neuronal death. The combination of non-excitotoxic calcium entry in response to oxidative stress and TRPM2 mediated excitotoxicity was abrogated after peptide treatment both in vivo and in vitro.

Advantages:

Targeting TRPM2 and its coupling with NMDARs provides a novel therapeutic strategy to tackle the devastating ischemic stroke
Uncoupling TRPM2-NMDAR interactions eliminate extra-synaptic toxicity while preserving pro-survival synaptic NMDAR function
Targeting TRPM2 provides a convergent inhibitory strategy to eliminate both non-excitotoxic and excitotoxic Calcium signal-mediated neuronal toxicity

Abstract:

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Potential Applications:

Market Application:

The peptide can be used to treat neurological injuries such as traumatic brain injury (TBI), hemorrhagic stroke, and ischemic stroke

Additional Information:

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Contact Information:

  • Name: Amit Kumar
  • Title :
  • Department :
  • Email : a.kumar@uconn.edu
  • Phone : (860) 486-6938
  • Address :