We recently announced our collaboration agreement with StrataStem, which will enable us to access and commercialize a large-scale collection of iPSCs derived from StrataStem’s Alzheimer’s Disease (AD) patient samples.

But what does this mean going forward? We’d like to outline the impact this will have on the world of iPSCs for Alzheimer’s Disease modelling and drug discovery, and the incredible potential of patient stratification with a “clinical trial in a dish”.

Alzheimer’s Disease: a growing problem

Alzheimer’s Disease (AD) is an irreversible, progressive neurodegenerative disease and the most common cause of dementia in the elderly today. Driven by an ageing population, it is estimated that by 2060, 14 million people in the US will be living with AD 1.

Despite a concerted research effort and a rise in drug candidates, no treatments for AD or other common dementias currently exist. The mechanism of action of many potential drug candidates is based on the amyloid hypothesis, whereby the accumulation of amyloid protein plaques causes progressive neuronal degeneration.

However, technological advancements in diagnostics and biomarkers have suggested AD is far more complex than first thought, with considerable heterogeneity in clinical presentation and pathophysiology 2. Modelling this complexity has been a major challenge that Biopharma, as yet, has not been able to overcome.

The current landscape of Alzheimer’s Disease models

Traditional animal-based models have provided some valuable insights but struggle to fully recapitulate the in vivo environment and complexities of AD pathophysiology 2. Post-mortem brain tissue from patients with Alzheimer’s Disease has provided valuable, human-relevant insights, but with the obvious downside of post-mortem studies.

As a promising avenue for disease modeling, human induced pluripotent stem cell (iPSC)-based models have sparked considerable research interest. Models built with human iPSCs have the potential to produce more human-relevant insights. With iPSCs derived from Alzheimer’s patients, it’s possible to build in vitro disease models using neurons and neuroinflammatory cells implicated in the disease pathophysiology.

At Axol, we’re using human iPSCs to create sophisticated co-culture models that exhibit hallmarks of Alzheimer’s Disease. Although useful and effective, these models have been created from single donors or a small number of donors, so there is still room to further explore the complexity of AD.

The inherent phenotypic and genotypic variability in AD makes early diagnosis and stratification of patients challenging. With the lack of effective diagnostic methods (current estimates of 25% misclassification) and no single genotypic marker, there is an urgent need for larger-scale models with additional power.

Using iPSCs for Alzheimer’s modeling: A cohort-scale trial-in-a-dish

Armed with a large library of fully consented patient donor samples, this agreement with StrataStem will enable us to apply our iPSC expertise on a large scale, with incredibly exciting implications for AD research.

Applying our knowledge of iPSCs, we can turn this substantial library of donor material into human iPSCs which can then be differentiated into a range of end-point cell types, comprising the various neurons and neuroinflammatory cells we know to be implicated in AD pathophysiology.

With a large, diverse range of donor samples, we think this could effectively provide a cohort-scale model in a dish, enabling drug discovery companies to test potential therapies, at scale, efficiently in a lab: a “Clinical Trial In A Dish“.

Furthermore, we believe that building this patient library enables patient stratification, whereby potential therapies could be tested to identify the profiles of individuals who respond better to each therapy, maximizing the success of later-stage clinical trials. This could be transformative for both the speed and success of drug development, de-risking the process and accelerating the path to better, more effective treatments.

As an increasingly prevalent neurodegenerative disease, the need for new AD therapies is only going to increase. But with this new agreement, and buoyed by the FDA Modernization Act 2.0, we’re committed to taking on that challenge and utilizing the full potential of human iPSCs to benefit patients worldwide.

Key takeaways: human iPSCs for Alzheimer’s drug discovery

• We’ve agreed an exclusive license with StrataStem to commercialize a large-scale collection of AD patient samples
• Using our iPSC expertise, we will develop these donor cells into cohort-scale in vitro models for drug discovery, aka a “Clinical Trial In A Dish”
• The power of this platform comes from patient stratification, where we can test potential therapies against these models to identify the profiles of patients who respond better, maximizing later-stage clinical trials and de-risking the process

Read about our announcement here: StrataStem and Axol Bioscience Announcement

 

1 2021 Alzheimer’s disease facts and figures. Alzheimers Dement. 2021 Mar;17(3):327-406. doi: 10.1002/alz.12328. Epub 2021 Mar 23. PMID: 33756057.

2 Young-Pearse TL, Lee H, Hsieh YC, Chou V, Selkoe DJ. Moving beyond amyloid and tau to capture the biological heterogeneity of Alzheimer’s disease. Trends Neurosci. 2023 Apr 3:S0166-2236(23)00067-X. doi: 10.1016/j.tins.2023.03.005. Epub ahead of print. PMID: 37019812.