For over three decades the treatment for strokes remain limited. Ischemic stroke is the leading cause of long-term disability around the world and is characterized by the sudden onset of neurological deficits following stroke. There is a notable absence of therapeutic drug interventions to mitigate brain damage and facilitate post-stroke recovery.
Currently either rapid use of a clot-busting medication called tPA or surgical removal of a clot from the brain with mechanical thrombectomy. However, only 5% to 13% percent of stroke cases are actually eligible for these interventions.
Note: The current Gold Standard is the IV injection of recombinant tissue Plasminogen Activator (tPA) The two types of TPA are alteplase (Activase) and tenecteplase (TNKase). An injection of TPA is usually given through a vein in the arm within the first three hours. Sometimes, TPA can be given up to 4.5 hours after stroke symptoms started. Sometimes it's possible to treat ischemic strokes directly inside the blocked blood vessel.
Now scientists at the UConn School of Medicine has developed a novel approach to the problem. Their team believe they have found a new innovative therapy to try to stop a stroke's "fire" or inflammation. Note that Once brain cells and tissue are damaged by a stroke, nothing can help restore the damage. The novel approach could effectively control a stroke's damage and turn back time.
They rely on the power of the MicroRNA (miRNA). MiRNAs are small RNA molecules that help cells to regulate multiple gene and protein expression. During a stroke these miRNA get dysregulated, thus leading to brain damage by multiple unchecked proteins.
Their research has confirmed the presence of increased levels of one such miRNA, known as miRNA-141-3p, in blood samples of stroke patients. Subsequently they we have successfully synthesized and tested a novel miRNA-141-3p inhibitor.
PS:
Abstract:
MicroRNA-141-3p plays a detrimental role in the pathology of ischemic stroke, presenting a new target for stroke treatment. This study introduces and validates a novel class of peptide nucleic acid (PNA)-based miR-141-3p inhibitors known as serine gamma PNA-141 (sγPNA-141) for ischemic stroke treatment. After synthesis, physicochemical characterization, and nanoparticle encapsulation of sγPNA-141, we compared its safety and efficacy with traditional phosphorothioate- and regular PNA-based anti-miR-141-3p (PNA-141) in vitro, followed by detailed in vivo and ex vivo efficacy testing of sγPNA-141 for treating ischemic stroke using a mouse model. sγPNA-141 demonstrated higher affinity and specificity toward miR-141-3p, and when applied post-stroke, demonstrated decreased brain damage, enhanced neuroprotective proteins, reduced tissue atrophy, swift improvement in functional deficits, and improvement in learning and memory during long-term recovery. Overall, our data show sγPNA-141 has neuroprotective and neuro-rehabilitative effects during stroke recovery. Furthermore, we demonstrated sγPNA-141’s effects are mediated by the TGF-β-SMAD2/3 pathway. In summary, the present findings suggest that sγPNA-141 could be a potentially novel and effective therapeutic modality for the treatment of ischemic stroke.
Currently either rapid use of a clot-busting medication called tPA or surgical removal of a clot from the brain with mechanical thrombectomy. However, only 5% to 13% percent of stroke cases are actually eligible for these interventions.
Note: The current Gold Standard is the IV injection of recombinant tissue Plasminogen Activator (tPA) The two types of TPA are alteplase (Activase) and tenecteplase (TNKase). An injection of TPA is usually given through a vein in the arm within the first three hours. Sometimes, TPA can be given up to 4.5 hours after stroke symptoms started. Sometimes it's possible to treat ischemic strokes directly inside the blocked blood vessel.
Now scientists at the UConn School of Medicine has developed a novel approach to the problem. Their team believe they have found a new innovative therapy to try to stop a stroke's "fire" or inflammation. Note that Once brain cells and tissue are damaged by a stroke, nothing can help restore the damage. The novel approach could effectively control a stroke's damage and turn back time.
They rely on the power of the MicroRNA (miRNA). MiRNAs are small RNA molecules that help cells to regulate multiple gene and protein expression. During a stroke these miRNA get dysregulated, thus leading to brain damage by multiple unchecked proteins.
Their research has confirmed the presence of increased levels of one such miRNA, known as miRNA-141-3p, in blood samples of stroke patients. Subsequently they we have successfully synthesized and tested a novel miRNA-141-3p inhibitor.
PS:
Abstract:
MicroRNA-141-3p plays a detrimental role in the pathology of ischemic stroke, presenting a new target for stroke treatment. This study introduces and validates a novel class of peptide nucleic acid (PNA)-based miR-141-3p inhibitors known as serine gamma PNA-141 (sγPNA-141) for ischemic stroke treatment. After synthesis, physicochemical characterization, and nanoparticle encapsulation of sγPNA-141, we compared its safety and efficacy with traditional phosphorothioate- and regular PNA-based anti-miR-141-3p (PNA-141) in vitro, followed by detailed in vivo and ex vivo efficacy testing of sγPNA-141 for treating ischemic stroke using a mouse model. sγPNA-141 demonstrated higher affinity and specificity toward miR-141-3p, and when applied post-stroke, demonstrated decreased brain damage, enhanced neuroprotective proteins, reduced tissue atrophy, swift improvement in functional deficits, and improvement in learning and memory during long-term recovery. Overall, our data show sγPNA-141 has neuroprotective and neuro-rehabilitative effects during stroke recovery. Furthermore, we demonstrated sγPNA-141’s effects are mediated by the TGF-β-SMAD2/3 pathway. In summary, the present findings suggest that sγPNA-141 could be a potentially novel and effective therapeutic modality for the treatment of ischemic stroke.
