New drug could flip the script for stroke treatment, but small Canadian biotech needs funding boost
Researchers used a new peptide drug in an animal model of severe ischemic stroke and found that it improved motor function, sensory function, spatial learning and memory. (iStock / Getty Images Plus)
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Once a stroke happens, the damage can’t be repaired by any drug on the market. But scientists think they have found an option that could protect and repair the damage that occurs with a stroke up to a week after onset—but limited resources may block its path to clinic. Providing the right conditions for science to thrive is crucial to uncovering a cure for cancer. Discover ways to cultivate an environment for growth to ultimately make an impact for patients.
There’s only one drug on the market for stroke treatment: Activase, sold by Roche’s Genentech, has to be administered within 4.5 hours of stroke onset. Most investigational stroke therapies currently under investigation also must be given within one to two days of the condition’s onset.
Researchers now believe they have identified a peptide that could change the script entirely for stroke treatment.
Scientists at the University of Cincinnati and Case Western Reserve University in Cleveland have found that the drug, dubbed NVG-291-R, supports nervous system repair and significant functional recovery in an animal model of severe ischemic stroke, as published in Cell Reports.
NVG-291-R reduced neuronal death and showed neuroreparative effects in animal models. The drug repaired damage by forming new neuronal connections and boosting migration of new neurons to the damaged site.
The researchers used NVG-291-R to block signaling pathways known as chondroitin sulfate proteoglycans, resulting in significant behavioral recovery including improved motor function, sensory function, spatial learning and memory. Researchers also found the drug to be effective even when administered as late as seven days after stroke onset.
NervGen Pharma, a clinical-stage biotech based in Canada, currently holds the rights to NVG-291-R and is planning trials in different neuronal damage diseases. Though the aforementioned research assessed the drug’s effect in neurorepair after stroke, NervGen is first launching clinical trials in patients with spinal cord injury, Alzheimer’s disease and multiple sclerosis, starting in 2022 and 2023.
When asked about the absence of stroke patients in its upcoming trial plans, the biotech cited limited resources. NervGen’s initial focus is based on the weight of scientific evidence to support those indications, the potential for positive impact on patients, feasibility of development, investor sentiment and commercial potential.
“Given this compelling new preclinical data in stroke, we believe there is a solid opportunity to secure non-dilutive funding to advance the program in the clinic through a partnership, either with industry or government,” NervGen said.
Activase® (alteplase) is indicated for the treatment of acute ischemic stroke. Exclude intracranial hemorrhage as the primary cause of stroke signs and symptoms prior to initiation of treatment. Initiate treatment as soon as possible but within 3 hours after symptom onset.
Activase is indicated for use in acute myocardial infarction (AMI) for the reduction of mortality and reduction of the incidence of heart failure.
Limitation of Use: The risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose AMI puts them at low risk for death or heart failure.
Activase is indicated for the lysis of acute massive pulmonary embolism (PE), defined as:
- Acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments.
- Acute pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures.
Important Safety Information
Do not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit: current intracranial hemorrhage (ICH); subarachnoid hemorrhage; active internal bleeding; recent (within 3 months) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding (e.g., some neoplasms, arteriovenous malformations, or aneurysms); bleeding diathesis; and current severe uncontrolled hypertension.
Do not administer Activase to treat acute myocardial infarction or pulmonary embolism in the following situations in which the risk of bleeding is greater than the potential benefit: active internal bleeding; history of recent stroke; recent (within 3 months) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding; bleeding diathesis; and current severe uncontrolled hypertension.
Warnings and Precautions
Activase can cause significant, sometimes fatal internal or external bleeding, especially at arterial and venous puncture sites. Avoid intramuscular injections and trauma to the patient. Perform venipunctures carefully and only as required. Fatal cases of hemorrhage associated with traumatic intubation in patients administered Activase have been reported. Aspirin and heparin have been administered concomitantly with and following infusion with Activase in the management of acute myocardial infarction and pulmonary embolism. The concomitant administration of heparin and aspirin with and following infusions of Activase for the treatment of acute ischemic stroke during the first 24 hours after symptom onset has not been investigated. Because heparin, aspirin, or Activase may cause bleeding complications, carefully monitor for bleeding, especially at arterial puncture sites. Hemorrhage can occur 1 or more days after administration of Activase, while patients are still receiving anticoagulant therapy. If serious bleeding occurs, terminate the Activase infusion, and treat appropriately.
In the following conditions, the risks of bleeding with Activase are increased and should be weighed against the anticipated benefits: recent major surgery or procedure; cerebrovascular disease; recent intracranial hemorrhage; recent gastrointestinal or genitourinary bleeding; recent trauma; hypertension; acute pericarditis; subacute bacterial endocarditis; hemostatic defects including those secondary to severe hepatic or renal disease; significant hepatic dysfunction; pregnancy; diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions; septic thrombophlebitis or occluded AV cannula at seriously infected site; advanced age; and patients currently receiving oral anticoagulants, or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.
Hypersensitivity, including urticarial / anaphylactic reactions, have been reported after administration of Activase. Rare fatal outcome for hypersensitivity was reported. Angioedema has been observed during and up to 2 hours after Activase infusion in patients treated for acute ischemic stroke and acute myocardial infarction. In many cases, patients received concomitant angiotensin-converting enzyme inhibitors. Monitor patients treated with Activase during and for several hours after infusion for hypersensitivity. If signs of hypersensitivity occur, e.g. anaphylactoid reaction or angioedema develops, discontinue the Activase infusion and promptly institute appropriate therapy (e.g., antihistamines, intravenous corticosteroids, epinephrine).
The use of thrombolytics can increase the risk of thrombo-embolic events in patients with high likelihood of left heart thrombus, such as patients with mitral stenosis or atrial fibrillation. Activase has not been shown to treat adequately underlying deep vein thrombosis in patients with PE. Consider the possible risk of re-embolization due to the lysis of underlying deep venous thrombi in this setting.
Cholesterol embolism, sometimes fatal, has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown. It is associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.
Coagulation Tests May be Unreliable during Activase Therapy
Coagulation tests and/or measures of fibrinolytic activity may be unreliable during Activase therapy unless specific precautions are taken to prevent in vitro artifacts. When present in blood at pharmacologic concentrations, Activase remains active under in vitro conditions, which can result in degradation of fibrinogen in blood samples removed for analysis.
The most frequent adverse reaction associated with Activase therapy is bleeding.
Please see full Prescribing Information for additional Important Safety Information.