Axol Bioscience has been awarded a SMART Grant by Scottish Enterprise to Accelerate ALS Research through the development of ALS-related phenotypes using human iPSCs. This represents another significant step towards better disease modelling and ALS drug discovery.
The key objectives of this project are to:
- Develop a quality manufacturing system for iPSC-derived ALS relevant cell types
- Characterise and validate the cells using ALS relevant end points; TDP43 aggregation, Neurofilament Light elevation and Cryptic Exon Sequencing
- Develop and characterise an ALS co-culture model which includes motor neurons, microglia and astrocytes
- Commercialise an easy-to-use model system to drive forward ALS drug discovery
We at Axol Bioscience, world leaders in human induced pluripotent stem cell (iPSC) manufacturing, consistently and at scale, are proud to announce that we have been awarded a SMART Grant by Scottish Enterprise. This significant milestone is a testament to our commitment to advancing cutting-edge research and innovation in the iPSC space.
SMART Grants support ambitious research and development (RCD) projects, in small and medium enterprises (SMEs), across Scotland and will enable Axol to accelerate the development of ALS-related phenotypes using our iPSCs. The award comes at a pivotal time as the scientific community intensifies its focus on developing better human- relevant in vitro models, for neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS). The grant will be instrumental in advancing our ability to support this industry-wide effort and unlocking new insights into ALS pathogenesis for ALS drug discovery.
Working with urgency to build better models of ALS
ALS is the most common form of motor neuron disease, where the progressive destruction of motor neurons leads to loss of muscular functions including walking, talking, swallowing and breathing. There is currently no cure. With treatment aimed at symptomatic relief and prolonging survival, most patients live only 3-5 years from the onset of symptoms.
With limited treatment options available and a predicted 69% increase in cases by 2040, attention has turned to in vitro ALS models that use human iPSCs from healthy or ALS patient donors. We, along with many others, are working with urgency towards developing higher quality and more relevant human in vitro tools, to support effective drug discovery.
Part of our recent work in the ALS space has included the launch of the axoCells(TM) ALS toolbox in September. This toolbox includes iPSC-derived motor neurons derived from 6 donor lines, that ALS researchers can use to accelerate their motor neuron research. These lines are from:
- Two unaffected donors; (ax0076: From a male donor, 40-50 years old at time of donation, and ax0078: From a male donor, 74 years old at time of donation)
- A C9orf72 carrying donor (ax0073: From a C9orf72 male who asymptomatic at time of He is the sibling to ax0074 donor. 62 years old at time of donation)
- Three ALS donors: (ax0735: From a female ALS donor with SOD1 mutation, 61 years old at time of donation, ax007G: From a female ALS donor with TDP43 mutation, 62 years old at time of donation, and ax0074: From a female ALS donor with C9orf72 mutation, 64 years old at time of donation)
We aim to continue to meet the needs of our customers and support the wider ALS community. The launch of the ALS toolbox represented a big step towards this aim, and we look to continue to make significant strides on this fight against ALS, with the SMART Grant.
Why the SMART Grant Matters for iPSCs and ALS Research
The SMART Grant is part of a broader push to scale the impact of Scotland’s innovation strengths, with a focus on projects that contribute to economic transformation. iPSCs are a prime example of a technology with immense growth potential. By enabling the generation of highly relevant human disease models, iPSCs are revolutionising drug discovery, particularly in areas such as ALS. This grant recognises the potential of iPSCs and positions Axol as a key player in this high-growth sector.
Grants like the SMART grant are crucial for driving innovation in sectors like these. iPSCs hold enormous potential for transforming drug discovery and disease modeling, but the complexity of developing reliable, scalable, and disease-specific models requires significant investment in both time and resources. By securing this grant, Axol will be able to continue developing and refining our ALS-related phenotypes, enabling us to provide the scientific community with even more powerful tools to advance ALS research.
How Axol are using the SMART Grant to push ALS research forward
Axol has identified an opportunity to lead the rapidly growing market in the development of human iPSC models in neurodegeneration. The SMART Grant will contribute towards a long-term project, where we aim to develop a human iPSC ALS co-culture model capable of accurately replicating the cellular environment of ALS across a diverse patient population, creating a groundbreaking “Clinical Trial in a Dish” (CTIAD) model.
This innovative approach would be unique in the market, providing a realistic and effective alternative to the animal models, currently used in ALS research and drug development.
Achieving this ambitious goal would require specialised expertise and cutting-edge technology, as it represents a market-first solution with the potential to transform ALS drug discovery and therapy development. We believe that our goal to develop a CTIAD model has the potential to revolutionise the drug discovery market, particularly in ALS research. This grant will allow us to build a proof-of-concept model that can be utilised in a wide range of applications.
What Axol aims to achieve with the SMART Grant Project
With this project, we aim to generate differentiated motor neurons from genetic ALS backgrounds and use them to develop quantitative phenotypic assays including Neurofilament Light (NF-L ELISA), biomarker expression and cryptic exon sequencing which are known to be elevated in patients with ALS. Current assays are not quantitative and have limitations in using these to screen drugs/therapeutics. Hence, there is a need to develop robust quantitative assays with a suitable assay window for screening drugs in a pre-clinical setting.
Once robust assays have been developed, we will generate a co-culture model designed to mimic an in vivo environment. This model will include disease-specific motor neurons cultured alongside astrocytes and microglia. Developing this highly complex system will require extensive optimisation to ensure all cell types can thrive together in the same culture conditions, while meeting their specific needs and maintaining this status long-term.
The successful completion of this SMART Grant project would result in a market- disrupting human co-culture model that demonstrates realistic and functional performance. This breakthrough technology will lay the foundation for future CTIAD models.
Currently, no commercially available ALS co-culture models exist on the market and with focused research, this project aims to rapidly commercialise these models to replace conventional animal testing methods. The project will take twelve months to complete and will achieve the following technical milestones:
- The generation of motor neuron progenitors containing SOD1 and TDP43 phenotype – (2 months)
- Characterisation of manufactured motor neurons through functional quality control testing and data generation – (2 months)
- The development and optimisation of quantitative phenotypic assays for the detection of TDP43 aggregates and Neurofilament Light elevation – (4 months)
- The development of HTFR/ELISA for the detection and analysis of molecular binding events or interactions – (4 months)
- The development of Cryptic Exon Sequencing Assay, utilising qPCR and specific primers optimisation, which will lead to the detection of various molecular changes, such as the release and inclusion of cryptic exons in diseased lines containing TDP43, UNC13a and STMN2 phenotypes – (4 months)
- The development and optimisation of Novel Co-Culture systems, using Astrocytes and Microglial cells, representing a “clinical trial in a dish” with comparative analysis of patient (affected) cells vs cells from unaffected donors (control) – (6 months)
- Data generation for testing of ALS co-culture using the quantitative phenotypic assays – (4 months)
“We are thrilled to be awarded this SMART Grant from Scottish Enterprise. The site here in Roslin, Edinburgh has a long history in stem cell technology, dating back to Dolly the Sheep.” said Mhairi Rodgers, Head of Operations at Axol Bioscience, “With this grant, we will accelerate our quality rich development of a human relevant ALS model to support much needed drug discovery”
Join us at the 35th International Symposium on ALS/MND
We are excited to share that we will be attending the 35th International Symposium on ALS/MND this December, where we will present our latest work on ALS-related iPSC phenotypes. This event will be an excellent opportunity to connect with fellow researchers and industry experts, who are passionate about advancing ALS research.
If you are attending, we invite you to visit us at our booth (Booth 11) to learn more about how our iPSC models are transforming ALS research. Our team will be on hand to answer questions, discuss potential collaborations and provide more details about how the SMART Grant will accelerate our ongoing research.
Looking Ahead: A Stronger Future for ALS Research
The SMART Grant is a powerful validation of Axol’s leadership in the iPSC space and our unwavering commitment to driving innovation forward through collaboration and hard work. We are excited about the potential this grant will unlock and look forward to seeing the tangible impact it will have on ALS research in the coming months.
At Axol, we remain dedicated to providing researchers with the tools they need to support their ALS research and drug discovery efforts. We are confident that with continued support from initiatives, like the SMART Grant, we will be able to contribute to the development of better human-relevant models of ALS, that will ultimately improve the lives of patients living with ALS.
If you have any questions or would like to discuss a collaboration, contact us at operations@axolbio.com we would be happy to have a conversation.