University of Pittsburgh researchers have discovered a TAT-DP-2 peptide that protects neurons from damage following acute ischemic injury (stroke).
Description
Stroke is the main cause of serious long-term disability in the US, with ischemic stroke the most common form (80%). The loss of blood supply to areas of the brain can lead to neuron death. While thrombolytic therapy may restore blood flow to the affected area, irreversible neuronal cell damage may continue to occur, leading to long-term damage to the brain. This novel peptide has the potential to protect neurons from excitotoxic injury and delayed cell death in the tissue surrounding the cells directly impacted by stroke, preventing further neuronal damage, reducing the risk of long-term disability, and improving outcomes for patients.
Applications
Ischemic stroke
Advantages
No neuroprotective treatment options are available to prevent delayed damage to neuronal post-acute ischemic injury.
Kv2.1 channels mediate neuronal cell death by allowing the loss of cytoplasmic potassium, optimizing intracellular conditions for apoptosis. A novel peptide, TAT-DP-2, can permeate the membrane, dispersing Kv2.1 surface clusters. The dispersal of these clusters prevents the association of Kv2.1 with vesicle-associated membrane protein–associated protein A (VAPA), inhibiting delayed apoptosis by Kv2.1 channels. This novel approach, targeting Kv2.1 channels to inhibit delayed neuronal cell death, provides a new method to reduce neurological damage associated with ischemic stroke.
Invention Readiness
Previous research has shown overexpression of the carboxyl terminus (CT) of the cognate channel Kv2.2 disrupts Kv2.1 surface clusters and is neuroprotective. Further experiments identified a key domain within the Kv2.2 CT (DP-2); in murine ischemia-reperfusion models, this domain was shown to be neuroprotective. Based on these findings, a peptide, TAT-DP-2, has been synthesized. This injectable peptide has been found to permeate the blood-brain barrier and provide neuroprotection in vitro. Murine studies following ischemic stroke showed this novel peptide targeted disruption of Kv2.1 surface clusters and disrupted interactions between Kv2.1 and VAPA with no binding between TAT-DP-2 and VAPA observed. Further work is required to understand the potential to use this in humans and other neurodegenerative conditions.
IP Status
https://patents.google.com/patent/US11673916B2
