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Proteinopathy Exploration Package

Providing a holistic view on the efficacy of your drug candidates to combat Tau, α-Syn and TDP-43 aggregation

Unveiling therapies for tomorrow's minds

ONE FOR THE MANY
 

The mislocalization and accumulation of protein aggregates is a shared hallmark for multiple neurodegenerative disorders (NDDs). Production of abnormal proteins is an important driver of Alzheimer’s, Parkinson’s disease, and Amyotrophic Lateral Sclerosis (ALS) as well as other NDDs categorized as proteinopathies.

Therefore, finding drugs that can prevent or eliminate the formation of protein aggregates in neurons has the potential to become an effective treatment for more than one proteinopathy.

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Start looking at your discovery programs from a new perspective with the Proteinopathy
Exploration Package

We have developed three robust assays that allow you to examine both early and late stages of aggregation and the impact on additional disease-linked phenotypes.

This is a suite of drug discovery assays that puts together the latest understanding of disease and human iPSC technology to catalyze the identification of drug candidates targeting Tau, a-Syn and/or TDP- 43 aggregation in neurons.

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Purpose-built to increase confidence

This assay suite recapitulates the aggregation of Tau, α-Syn and TDP-43 in human iPSC-derived neurons and provides clinically relevant readouts to understand the impact of your compounds on both early and late stages of aggregation. As these models are based on human iPSC-derived neuronal subtypes, they are close to human pathophysiology and enable the analysis of additional disease-linked phenotypes.

Designed to deliver robust and reproducible data

The three assays are robust and fully automated to accurately measure the impact of your drug candidates in early and late aggregation of Tau, α-Syn and TDP-43. The precision and robustness of the assays are strong enough to take action from the results (Z factor > 0.5 and %CV < 10%). Automation also comes with speed: all three models are run in parallel, which significantly reduces costs and waiting times when compared to animal models.

Formed to catalyze drug discovery

With the Proteinopathy Exploration Package your results are ready in 6 weeks. The fully automated assay suite is amenable for 96 and 384 well plate formats. Data analysis is a smooth and quick with our in-house developed algorithms and analytics tools. Get the report in your hands to make decisions, without delaying progress.

Benefits of Ncardia's Proteinopathy Exploration Package

Increased Confidence

Human models and robust data

Amenable for HTS

Fully automated

Results in 6 Weeks

Three models screen in parallel

From Hit identification to Lead optimization, having a human-based automated assay with clinically relevant readouts puts you on an ideal position to make data-driven decisions and mitigate risks

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Get a holistic view on the efficacy of your drug candidates to combat Tau, α-Syn and TDP-43 aggregation

By screening your compounds in three models in parallel you will gain deep understanding of the action of your compounds in key neurodegenerative disorders, helping you know more to select the most promising candidates sooner.

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What you get with the Proteinopathy Exploration Package

Tau α-Synuclein TDP-43

In vitro assessment of Tau aggregation

With a lentiviral transduction of Tau and chronic treatment with Tau PFFs of Ncardia’s human iPSC-derived cortical neurons we can recapitulate the increase in MC-1 and phospho-Tau, the initial stages of protein aggregation. Formation of insoluble Tau aggregates is also modeled as demonstrated by the results after treatment with methanol.

In vitro assessment of Tau aggregation in human iPSC-derived neurons using High Content Imaging

In vitro assessment of α-Synuclein aggregation

Acute treatment of Ncardia’s human iPSC-derived cortical neurons with PFFs induces a significant increase in the formation of puncta phospho- α-Syn when compared to untreated neurons. Chronic treatment can further increase the phenotype. To show the potential of the assay, disease neurons were treated with inhibitors of the protein degradation pathway and activators of lysosomal activity. Both treatments showed the expected phenotype rescue effect.

In vitro assessment of a-synuclein aggregation in human iPSC-derived neurons using high content imaging

In vitro assessment of TDP-43 aggregation

We have developed a protocol for the maturation of human iPSC-derived motor neurons with both wild type and TDP-43 CRISPR engineered lines*. After maturation, mutant TDP-43 motor neurons show mis-localization and aggregation of TDP-43. Addition of a chemical stressor can further enhance the phenotype. Based on this model, we have optimized a HTRF assay to quantify the aggregation of TDP-43 as part of the Proteinopathy Exploration Package.  Additional assays for TDP-43 mis-localization and STMM2 mis-splicing are also available at Ncardia.

 * iCell(R) Motor Neurons, 01279 from FUJIFILM Cellular Dynamics, Inc

Quantification of the normalized TDP-43 aggregation in human iPSC-derived motor neurons by HTRF

Want to know more?

Using the Proteinopathy Exploration Package and complementary Ncardia assays we can assess protein aggregation and other disease-linked phenotypes relevant to Alzheimer's, Parkinson's and Amyotrophic Lateral Sclerosis, among other neurodegenerative disorders. 

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Explore our Case Studies

Discover more about our Solutions for Neurodegenerative Drug Discovery

 

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If you're ready to start looking at your drug discovery programs from the unique perspective offered by the Proteinopathy Exploration Package, we'd welcome the opportunity to introduce you to our experts.

Charles Leach Business Development Manager
Charles Leach, BD manager