Anti-stroke biologics: from recombinant proteins to stem cells and organoids Presented by - Zarghoona Jawad Zaynah Arafath Nadha Imthiyaz Presented to – Dr. Sumera
Abstract Stroke, a cerebrovascular disease, is the second most common cause of death, and the leading cause of disability with high morbidity worldwide.
Types of strokes
Tenecteplase current clinical trials show that two recombinant proteins, tenecteplase and non-immunogenic staphylokinase, are most promising as new thrombolytic agents for acute ischaemic stroke therapy
Staphylokinase
Introduction to Stem Cells for Stroke Therapy
Mechanisms of Stem Cell Therapy in Stroke
Clinical Trials and Stem Cell Types Clinical Trials : Mostly Phase I or II, focusing on safety and initial efficacy. Stem Cell Types : MNCs : Diverse cell collection, easy accessibility, no immune rejection. MSCs : Self-renewal, immune tolerance, and low tumorigenicity. NSCs : Differentiation into neural cells, promising but with ethical concerns.
Routes and Dosage of Administration Administration Routes : Intravenous (IV) : Minimally invasive but limited cell delivery to the brain. Intra-arterial (IA) : Better delivery but risk of vascular complications. Intracerebral (IC) : High cell engraftment, invasive. Intrathecal : Less invasive, unclear engraftment rates. Alternative Methods : Intranasal and hydrogel-based delivery. Dosage : Typically 10⁶ to 10⁹ cells, varying by phase and route.
Timing of Administration and Outcome Measures Therapeutic Time Windows : Acute Stage : Few days to 1 month post-stroke. Subacute Stage : Few weeks to 6 months. Chronic Stage : 6 months or longer. Optimal Timing : Early transplantation (hours to days) yields the best outcomes. Outcome Measures : Modified Rankin Scale, NIH Stroke Scale, Barthel Index frequently used in trials to assess efficacy.
The challenges of stem cell therapy for stroke Identifying the optimal cell type and timing tailored to different stroke subtypes. ensuring the survival, integration, and appropriate differentiation of transplanted stem cells within the injured brain. Standardizing protocols for stem cell preparation, quality control, and delivery methods. Evaluation and mitigation of safety risks.