Neuroprotective Agent Development
Neuroprotective agents are drugs that prevent, slow, or reverse neuronal damage in a given neurological disorder. At Protheragen, we firmly focus on providing advanced neuroprotective agent development services for exceptionally rare neurodegenerative diseases. We have considerable experience in drug discovery and development and support our clients from the early-stage research to the commercialization process.
Overview of Neuroprotective Agents for Rare Neurological Diseases
Neuroprotective agents are therapeutics intended to protect neurons from damage while slowing the progression of a disease in different disorder pathways. These agents play an important role in maintaining neural function in amyotrophic lateral sclerosis (ALS), as well as in Parkinson's and Huntington's diseases. Despite the numerous neuroprotective drugs that have been issued, the development of these drugs continues to face significant issues such as penetrating the blood-brain barrier (BBB), enduring long-term effectiveness, and coping with the intricate pathophysiological pathways of neurodegenerative disorders.
Fig. 1 Neuroprotective agents exert their effects through various mechanisms of action. (Pekdemir B, et al., 2024)
Mechanisms of Action of Neuroprotective Agents
Neuroprotective agents exert their therapeutic effects through multiple complementary pathways:
- Antioxidant Activity: Dismantles and eliminates oxidative species to reduce the risk of oxidative stress causing damage to the nerves.
- Glutamate Modulation: Controls the level of calcium in the cell by managing the excitatory neurotransmission in order to prevent excitotoxicity.
- Mitochondrial Support: Increases the output of energy to reinforce and improve the stability of mitochondria in the nerves.
- Anti-apoptotic Effects: Stops the pathways of programmed cell death so as to promote the survival of the nerves.
- Anti-inflammatory Action: Alters the activation of microglial cells and the subsequent release of cytokines involved in neuroinflammation, and thus neuroinflammation is reduced.
- Neurotrophic Enhancement: Stimulates growth factor signaling (e.g., BDNF, GDNF) to support neuronal growth and repair.
Development of Neuroprotective Agents for Rare Neurological Diseases
| Drug Names | Indications | Targets | Mechanism of Action | Development Phase |
| Edaravone | Amyotrophic lateral sclerosis | Reactive oxygen species (ROS) | Scavenges free radicals to reduce oxidative stress | Approved |
| Riluzole | Amyotrophic lateral sclerosis | Glutamate transporters | Inhibits glutamate release and modulates neuronal excitability | Approved |
| Idebenone | Friedreich's ataxia | Mitochondrial complex I/III | Enhances mitochondrial electron transport and energy production | Approved |
| Troriluzole | Alzheimer's disease | Glutamate transporters | Modulates glutamate signaling and synaptic plasticity | Phase III |
| BIIB080 | Alzheimer's disease | Tau mRNA | Reduces tau protein production to prevent neurofibrillary tangles | Phase I |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Designing neuroprotective agent therapies for rare motor neuron diseases and other rare neurological disorders is a service we provide at Protheragen, starting from target identification all the way through to preclinical studies. We also specialize in creating biological models to study the specific diseases, including in vitro and in vivo models, to accelerate the development of neuroprotective therapies and disease modification.
Neuroprotective Agent Development Services
Protheragen provides comprehensive neuroprotective agent development services covering a variety of molecular modalities, including small molecules, biologics, nucleic acid therapies, cell therapies, etc.
Workflow of Small Molecule Neuroprotective Agent Development
Target Identification & Validation
Using omics data from patients, CRISPR screenings in iPSC-derived neuronal or glial cells, and verifying through genetic animal models for confirming relevance and drug viability, targets with neuroprotective properties are prioritized employing the underlying mechanisms of diseases (excitotoxicity, oxidative stress, and neuroinflammation).
Hit Discovery & Lead Optimization
High-throughput screening integrates phenotypic assays (such as neurite outgrowth and synaptic activity) with target-based strategies, then refines these assays through medicinal chemistry for optimized BBB penetration, selectivity as well as enhanced PK/PD properties via tailored structure-activity relationship (SAR) and scaffold-hopping approaches.
In Vitro Characterization
Advanced mechanistic studies employ oxygen-glucose deprivation models and microglial activation assays alongside mitochondrial function evaluations in human iPSC-derived neural cells, in addition to biomarker analysis (LDH, ROS, and caspase activation) for quantifying neuroprotection.
In Vivo Efficacy Testing
In vivo efficacy studies incorporate pharmacokinetic/pharmacodynamic (PK/PD) evaluations to determine relevance for further development and utilize disease-specific animal models, behavioral, histopathological and functional endpoints. The studies establish correlates of dose-dependent efficacy with pharmacokinetic parameters, and translatability to humans is ensured through dose predictions made with PK/PD models.
Safety Assessment
A thorough evaluation of neurotoxicity comprises of Irwin tests, seizure propensity assays, and specialized neurobehavioral batteries along with histopathology to assess the safety margins of the central nervous system (CNS).
With extensive experience in neuroscience drug development, we provide end-to-end customized solutions for neuroprotective drug development. Whether you need a blood-brain barrier (BBB) permeable small molecule or a biologic, we can provide a mechanism-driven strategy based on your specific therapeutic goals. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Pekdemir B, Raposo A, Saraiva A, et al. Mechanisms and potential benefits of neuroprotective agents in neurological health[J]. Nutrients, 2024, 16(24): 4368.