Amyotrophic Lateral Sclerosis (ALS) Mouse Models

Biospective’s validated ALS animal models (including rNLS8 TDP-43ΔNLS and our proprietary "Low Dox" model variant) are purpose-built for neuroscience drug development. Our ALS mice feature motor deficits, cytoplasmic mislocalization & phosphorylated TDP-43 aggregates, neuroinflammation, and neurodegeneration. As a leading neuroscience CRO, Biospective delivers decision-ready in vivo data supported by translational biomarkers, including neurofilament light (NfL), to biotech & pharmaceutical companies.

Biospective specializes in Amyotrophic Lateral Sclerosis (ALS) models. We have developed industry-leading ALS mouse models and have deep expertise in TDP-43 pathology. As a global preclinical neuroscience contract research organization (CRO), we support biotech & pharmaceutical drug development programs using validated ALS animal models for therapeutic efficacy, target engagement, mechanism-of-action, biodistribution, and PK/PD studies across small molecules, antisense oligonucleotides (ASOs), gene therapy, antibodies, and other biologics.

Biospective’s TDP-43 mouse models (including the conventional "Off Dox" rNLS8 model and our proprietary, slower progressing "Low Dox" TDP-43ΔNLS model) recapitulate key features of human ALS, including phosphorylated protein aggregation in brain and spinal cord neurons, axonal degeneration, neuroinflammation, muscle atrophy, denervation of the neuromuscular junction (NMJ), and motor dysfunction. Studies include translational biomarkers, such as neurofilament light chain (NfL) in plasma and CSF, advanced neuroimaging, and quantitative multiplex immunofluorescence. With fully integrated, end-to-end preclinical services, and unmatched experience conducting ALS contract research studies in animal models, Biospective enables translational Amyotrophic Lateral Sclerosis research from study design through data analysis.

Why Choose Biospective as Your ALS Models CRO?

Biospective is a neuroscience CRO with a focus on ALS animal models, strong scientific expertise, and extensive experience conducting preclinical studies TDP-43 models.

• Specialized ALS Mouse Models CRO: Focused exclusively on ALS and neurodegenerative disease models, not a generalist animal provider.

• Multiple Validated ALS Models: "On Dox" and "Low Dox" rNLS8 mice are readily available for studies.

• TDP-43 Expertise: Deep scientific expertise in TDP-43 biology and pathology, a central misfolded protein in ALS.

• Integrated Services: Fully integrated preclinical services from study design to data interpretation, ensuring seamless execution.

• Proven Efficacy Data: Industry-standard TDP-43 efficacy datasets and extensive historical controls for robust benchmarking.

• In-House Transgenic Mouse Colony: Large internal colony of rNLS8 (TDP-43ΔNLS) transgenic mice, enabling large scale studies with well-characterized animals.

• Accelerated Timelines: Rapid study initiation and efficient workflows to compress timelines without sacrificing quality.

• Translational Biomarkers: Advanced biomarkers (NfL CSF/blood assays, in vivo MRI) that bridge preclinical findings to clinical outcomes.

• Flexible Study Designs: Our scientists work with your team to customize the study design to best fit your goals.

• Global Support: Experience supporting biotech and pharmaceutical industry clients worldwide, with responsive project management and communication.

Our scientists work as an extension of your internal team, collaborating closely to ensure scientific rigor, reproducibility, and translational relevance at every stage of your ALS drug discovery & development programs.

TDP-43 Mouse Models – Our Core Expertise

Biospective specializes in disease-relevant TDP-43 mouse models for ALS drug development.

TDP-43 protein aggregation is central to Amyotrophic Lateral Sclerosis pathophysiology. Biospective has built specialized capabilities around TDP43–based ALS animal models, making this competency a core differentiator of our CRO services.

These mouse models enable direct evaluation of target engagement and downstream neurodegenerative processes under pathological conditions. Notably, our TDP-43 models recapitulate key features of human ALS – including pTDP-43 (p409/410) aggregates, neurodegeneration, neuroinflammation, motor impairments, muscle weakness and wasting, and altered EMG. Our animal model portfolio emphasizes reproducibility, well-defined phenotypes, and the integration of behavioral, imaging, biochemical, molecular, and histopathological endpoints to enable comprehensive in vivo ALS therapeutic efficacy and exploration of mechanism-of-action studies.

Translational Pathology and Biomarkers in ALS Models

Biospective has established a broad range of clinically-relevant disease markers to facilitate translation to clinical studies.

As a Preclinical Neuroscience CRO, we design our ALS rodent models with translational relevance to mirror key aspects of the human disease. A major differentiator of Biospective is our focus on translational biomarkers that align preclinical findings with clinical outcomes – including fluid & advanced neuroimaging biomarkers. We incorporate:

• TDP43–related biomarkers (pathology and spread)

• Neuroinflammation markers (microglial/astrocyte activation)

• Neurodegeneration endpoints (axonal degeneration, atrophy)

• Mechanism-of-action confirmation (target/pathway engagement)

Our modeling and biomarker strategies ensure that preclinical successes meaningfully predict clinical potential, de-risking the transition from animal studies to human trials.

How are ALS Mouse Models Used in Drug Development?

We work closely with our biotech and pharmaceutical sponsors to:

• Evaluate therapeutic efficacy and dose-response in ALS models

• Assess target engagement and disease-modifying effects

• Support translational biomarker strategies, including fluid biomarkers (e.g. NfL) for clinical readiness

Our ALS mouse models are optimized for in vivo testing of multiple therapeutic modalities, including both traditional and advanced approaches:

End-to-End ALS Preclinical CRO Services

Biospective offers fully integrated preclinical ALS contract research services.

• Study design & model selection – expert guidance on choosing the most appropriate ALS model and designing robust studies

• In vivo efficacy studies – execution of treatment studies with thorough monitoring of outcomes

• Biodistribution & PK/PD – analysis of drug distribution and pharmacokinetics/pharmacodynamics in CNS and periphery

• Target engagement assays – confirmation that the therapeutic hits its molecular target (e.g. TDP-43 reduction, pathway modulation)

• Behavioral analysis – motor function testing (grip strength, hindlimb clasping, grill agility, etc.)

• In vivo multi-modality imaging – MRI, PET, SPECT, fluorescence, and bioluminescence imaging to track disease and treatment effects

• Immunoassays – biomarker quantification in CSF, blood, and tissue (e.g. NfL, cytokines, chemokines)

• Immunohistochemistry (IHC) & multiplex immunofluorescence (mIF) – post-mortem tissue staining & quantitative image analysis to assess pathology and therapeutic impact

• Data analysis & reporting – rigorous quantitative analysis, statistics, and comprehensive reporting by our scientists

This end-to-end approach minimizes handoffs, accelerates timelines, and reduces risk for our sponsors by keeping all aspects of the study under one expert team.