Modeling Alzheimer’s Disease with Certara IQ™

Introducing Certara IQ, an AI enabled modeling platform for scaling and democratizing QSP modeling. Certara IQ offers a range of model libraries licensed separately, spanning numerous pharmacologies and therapeutic areas.

In In this video, we are joined by Shana Schwartz, a TARANCE expert in the Alzheimer’s disease model as a part of the neuroscience QSB team. So, Shana, I want to begin by asking you about the Alzheimer’s disease QSB model. Why is this model a cutting edge tool for clients that are developing Alzheimer’s disease therapies today? Can you talk us through some of the features?

Certainly. Yes. Certara’s Alzheimer’s disease QSP platform is a game changer because it empowers drug developers to predict therapeutic performance and design smarter, more competitive clinical trials.

It’s very modular and customizable, so the architecture can change based on the client’s needs. It allows us to independently and jointly simulate both tau pathology, amyloid aggregation, and its intermediates, brain volume changes, neuroinflammation effects, and even ARIA ERisk.

Really allow us to capture how these processes interact in response to your, therapy to affect the clinical performance from early to late stage Alzheimer’s disease.

Now these models go beyond standard biomarkers, by modeling key mechanisms such as cytokine dynamics, Trem2 signaling, inflammasome activation, and microglial phenotype switching.

We’re able to account for things like tau synthesis, degradation, and release and uptake, at the synaptic cleft.

And really by examining and combining the effects of tau load, amyloid burden, as well as broader biological pathways of interest, specifically those involved in neuroinflammation.

We’re able to mechanistically link your drug action to neuronal firing patterns, cell survival rates, all the way to patient cognitive function, which is an ultimate measure for the clinical performance. Because really at the end of the day, we’re not only interested in understanding how tau and amyloid change as a function of a given therapeutic therapy, but, we’re also interested in really how these patients will respond to that therapy and how their memory function is going to improve.

Also, Certara’s Alzheimer’s disease platform supports, genotype specific predictions, such as those for APOE four carriers or individuals with variants affecting neurotransmission.

And this really enables a personalized safety and efficacy insights, for specific clinical trials in certain patient populations.

So here, we’re able to incorporate real world complexity, including potential interactions with commonly prescribed co medications, such as antipsychotics and antidepressants.

We also have the ability to model neuropsychiatric illnesses and motor dysfunction.

So in short, we really give clients the ability to test and refine therapies virtually using a well calibrated clinically calibrated model. And this allows clients to make predictions before entering the clinic, helping them to reduce risk, accelerate drug development, and increase their chances of success.

Thanks, Sheena. It’s a very impressive list of features you just talked through. The next thing I’m wondering is what are some of the practical advantages that this QSP model brings to organizations, especially when they’re thinking about the safety and efficacy of new therapies in Alzheimer’s disease?

So our Alzheimer’s disease platform simulates disease progression from mild cognitive impairment all the way through to late stage Alzheimer’s disease, allowing clients to test the right drug at the right stage.

So we can precisely model how changes in amyloid, in tau s u v r, or neuroimplement inflammatory signals translate into clinical outcomes, such as scores on cognitive scales like the clinical dementia rating sum of boxes scale. We are capable of generating very diverse, and large virtual patient populations that reflect real relevant genetic variability, such as APOE four status, as well as common neurotransmission variants.

And in addition to that, we can also account for the various co medications that these patients are commonly taking.

And this allows us to stratify analyses for safety and efficacy, giving you a deeper understanding of how your therapy will perform across different populations and subgroups of individuals.

And what this means for the client is it translates into smarter decisions for clients regarding who to enroll in your trial, what dose to choose, what administration schedule to provide.

It allows you to consider things like coadministration with another drug.

You can also, look at how likely clients are going to be able to observe shifts in things like ARIA ERisk, amyloid and tau PET signals, as well as other biomarkers.

So ultimately, you can look at whether, your mechanism of action is hitting the right biology.

So in short, our Alzheimer’s disease QSP platform accelerates data driven decisions so clients can move faster, reduce risk, navigate early drug development and clinical trial advancements, increasing their chances of a success.

Thanks, Sheena. I know our neuroscience, QSP team is equipped with various other, experiences in terms of other indications.

Can you talk to us about other neuroscience QSP models that Certara has experience with?

Certainly. The NeuroQSP team at Certara has numerous well curated and clinically calibrated models for schizophrenia, Parkinson’s disease, as well as progressive supranuclear palsy. And we also have many other capabilities and experience in modeling diseases such as multiple sclerosis, epilepsy, stroke, depression, bipolar, to mention a few.

Thank you, Shana.

Thank you so much for letting me take this time to share our NeuroQSP modeling capabilities.

With intuitive and scalable QSP model building, Certara IQ helps transform your drug development. To learn more about our Alzheimer’s disease and other neurodegenerative QSP models, visit our website.