PSD-95 Antibody: How to Open a New Era of Neuroprotection for Ischemic Stroke Treatment?.

1. What are the clinical challenges in treating ischemic stroke?

As the neurological disease with the highest global disability rate, ischemic stroke poses significant clinical challenges due to its narrow treatment window and irreversible neural damage. While the standard treatment alteplase can restore blood flow through thrombolysis, it carries high bleeding risks, has a short therapeutic window (typically ≤4.5 hours), and limited applicability. More importantly, reperfusion itself may trigger secondary injuries such as oxidative stress and excitotoxicity. Therefore, developing targeted drugs that can extend the treatment window and reduce neuronal death has become an urgent need in stroke therapy.

2. What is the neuroprotective mechanism of PSD-95 inhibitors?

PSD-95 (Postsynaptic Density Protein-95), as a scaffolding protein, plays a critical role in excitotoxic injury. Under ischemic stress, excessive glutamate release activates NMDA receptors, which through coupling with PSD-95 and neuronal nitric oxide synthase (nNOS), triggers massive nitric oxide (NO) production. Excess NO leads to neuronal apoptosis via multiple pathways including nitrosative stress, mitochondrial dysfunction, and DNA damage. PSD-95 inhibitors specifically block the PSD-95/nNOS interaction, effectively interrupting this death signaling pathway while preserving normal NMDA receptor physiological functions, providing a precise intervention strategy for neuroprotection.

3. What are the innovative aspects of the ESCAPE-NA1 clinical trial design?

This Phase III clinical trial adopted a multicenter, randomized, double-blind, placebo-controlled design, enrolling 1,105 acute ischemic stroke patients undergoing endovascular thrombectomy (EVT) across 48 global research centers. The study innovatively included a pre-specified subgroup analysis: dividing patients into those receiving standard alteplase treatment and those not receiving alteplase. This design was based on an important pharmacological discovery—that plasmin activated by alteplase may degrade the peptide inhibitor Nerinetide, potentially affecting its efficacy. The primary endpoint was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days, with secondary endpoints including neurological deficits, mortality, and imaging-based infarct volume.

4. What clinical efficacy evidence exists for Nerinetide?

In the pre-specified subgroup not receiving alteplase, Nerinetide demonstrated significant clinical benefits:

1. Improved functional recovery: 59.4% of treated patients achieved functional independence (mRS 0-2), significantly better than 49.8% in the placebo group, representing a 19.3% relative improvement;

2. Clear survival advantage: 40% reduction in all-cause mortality, indicating robust neuroprotective effects;

3. Imaging evidence support: MRI showed a 22% reduction in cerebral infarct volume, providing objective biological evidence of drug efficacy;

4. Extended treatment window: Maintained efficacy when administered within 12 hours of stroke onset, significantly prolonging the therapeutic opportunity window.

Notably, no significant benefit was observed in patients concurrently receiving alteplase treatment, validating the plasmin-mediated drug degradation hypothesis.

5. What is the clinical significance of PSD-95 inhibitors?

The success of Nerinetide marks an important shift in stroke treatment philosophy:

1. Therapeutic strategy innovation: Transitioning from simple vascular recanalization to a comprehensive "recanalization + neuroprotection" treatment model;

2. Treatment window breakthrough: Extending effective intervention time to 12 hours, significantly expanding the eligible patient population;

3. Precision medicine practice: Achieving personalized treatment plans through biomarker-guided patient stratification;

4. Mechanistic exploration value: First human validation of the PSD-95/nNOS signaling pathway as a clinically feasible stroke treatment target.

6. What are the future research directions and clinical translation prospects?

Based on key findings from ESCAPE-NA1, subsequent research will focus on:

1. Dosing strategy optimization: Exploring sequential treatment regimens administering Nerinetide before alteplase, such as in the FRONTIER trial implemented during ambulance transport;

2. Precise patient selection: Developing rapid detection methods to identify patient subgroups most likely to benefit;

3. Combination therapy exploration: Investigating synergistic effects with other neuroprotective agents;

4. Application scope expansion: Potential value in other acute neurological injuries like traumatic brain injury and subarachnoid hemorrhage.

These studies will further clarify the position of PSD-95 inhibitors in acute neurovascular disease treatment.

7. ConclusionThe breakthrough progress of PSD-95 inhibitor Nerinetide in acute ischemic stroke treatment marks a crucial step from concept validation to clinical practice. Its unique mechanism of action, favorable safety profile, and significant clinical efficacy—particularly the clear benefits for patients not receiving alteplase—provide a new direction for stroke treatment. With further in-depth research, PSD-95-targeted treatment strategies are expected to reshape the therapeutic landscape of acute ischemic stroke, bringing hope to more patients.

8. Which manufacturers provide PSD-95 antibodies?Hangzhou Start Biotech Co., Ltd. has independently developed the "PSD-95 Recombinant Rabbit Monoclonal Antibody" (Product Name: PSD-95 Recombinant Rabbit mAb (S-1518-4), a high-specificity, excellent sensitivity, and outstanding staining consistency neurobiology research tool. This product was developed using recombinant rabbit monoclonal antibody technology and has been rigorously validated across multiple platforms including immunohistochemistry (IHC), Western Blot (WB), and immunofluorescence (IF). It holds critical application value in synaptic structure and function research, neural development, and exploration of mechanisms in psychiatric and neurological disorders.

Professional Technical Support: We provide comprehensive product technical documentation, including staining protocols for brain tissue sections and neuronal cultures, multicolor immunofluorescence labeling recommendations, and professional image analysis guidance, fully assisting customers in obtaining accurate and reliable experimental results in neuroscience research.

Hangzhou Start Biotech Co., Ltd. is committed to providing high-quality, high-value biological reagents and solutions to global innovative pharmaceutical companies and research institutions. For more details about the "PSD-95 Recombinant Rabbit Monoclonal Antibody" or to request sample testing, please contact us.

Product Information