Back in September 2022, Axol Bioscience identified ALS as a key disease area that would significantly benefit from iPSCs, cellular models, and assays. From there, we began a deliberate and focused journey to build our competency within this disease thematic for drug discovery. We started by identifying patient‑specific iPSC lines for SOD1, C9orf72, and TDP‑43. In parallel, our talented team worked on accelerating the maturation time required for these cells to become assay‑ready. I am pleased to share that we achieved a 21‑day maturation timeline, which is now industry-leading, best-in-class.
However, what we were ultimately seeking was a robust functional phenotype, which we were able to identify very quickly, consistently, and reproducibly across both our ALS‑affected and unaffected cells. Initially, this was achieved through electrophysiological and functional readouts on the Axion BioSystems Maestro Pro™ platform and the Sartorius Incucyte® live‑cell analysis system. Since then, our capabilities have expanded through collaborations with additional MEA and high‑content imaging partners, and more recently through the Nanion SyncroPatch 384 automated patch‑clamp platform for detailed ion and sodium channel expression analysis. In addition, we set out to validate clinically relevant endpoint assays, including those assessing TDP‑43 mislocalisation and neurofilament light chain (NfL) levels.
The above enables Axol to have the essential tools to build more complex co‑culture models in the ALS disease space, allowing us to measure both phenotypic and functional differences across ALS‑affected and unaffected cell lines and 2D cultures. These models include:
- Motor neurons / microglia
- Motor neurons / skeletal muscle
- Motor neurons / microglia / astrocytes
We went about developing an assay tool kit, supported financially through a SMART grant from Scottish Enterprise, comprising the following validated endpoint assay products:
- ax0076 – axoCells™ human iPSC-derived motor neurons (unaffected), male donor, aged 40-50, ≥2 million cells
- ax0073 – axoCells™ human iPSC-derived motor neurons (unaffected, C9orf72 carrier), male donor, aged 62, ≥2 million cells
- ax0074 – axoCells™ human iPSC-derived motor neurons (sALS, C9orf72), female donor, aged 64, ≥2 million cells
- ax0079 – axoCells™ human iPSC-derived motor neurons (sALS, TDP-43), female donor, aged 62, ≥2 million cells
- ax0735 – axoCells™ human iPSC-derived motor neurons (sALS, SOD1), female donor, aged 61, ≥2 million cells
Axol Bioscience was one of the first companies founded around iPSC technology, and over the past 13 years, we have come to recognise that cell lines behave differently depending on the source of the original bio-sample. We also understand that the greatest impact and potential benefit for patients with ALS and Alzheimer’s disease would be achieved if we could expand our cell models to the sporadic forms of these diseases, as they represent a much larger affected population with no familial link.
We started talking to the research community, CROs, BioPharma, and Pharma partners about our ambition to build a platform that addressed the sporadic forms of the disease, and it was, to say the least, frustrating. We had unanimous support that what we wanted to build was absolutely needed, and that there would be demand for such a platform. However, given where the industry has been for the last three years, “constraint of capital was absolutely the limiting factor”.
We did not give up. We kept spreading the message, and we kept knocking on doors until we found another true believer in the form of LifeArc and Zhi Yao. Over the last 20 months, we have been working to put together PRISM, and along the way, we have picked up two more true believers in ALS TDI and a big Pharma partner who wishes to remain anonymous at this point in time.
Axol Bioscience’s commitment to PRISM is reflected in the deliberate way we have built our capability and confidence in the ALS disease space, supported throughout by repeated studies, robust data, and validation. Our conviction in the science and in the urgent need for such a platform for ALS patients worldwide is so strong that we are building this platform at cost. In return, we retain commercial rights, and PRISM partners receive preferential status.
Phase I is underway in earnest under the scientific leadership of Sapna Vyas and supported by the broader Axol Bioscience team. We expect this to be completed in 12-18 months, and we will communicate progress at that point in time, as well as seek top-up funding based on a successful Phase I.
As I have said on several occasions, “science is a journey for the truly committed”, and with that in mind I want to give credit and thanks to the following people who have made a material impact on Axol Bioscience’s ALS journey to date: Sapna Vyas, Zhi Yao, Ashley Barnes, Paul Wright, Fernado Vieira, Jessica Tilman, David Wallbank, Hannah Sharplin, Stuart Prime and Scottish Enterprise.
The PRISM collaboration represents a key milestone in our three-and-a-half-year journey to build a world-first commercially validated sporadic disease iPSC platform for the benefit of ALS patients worldwide. The project aligns perfectly with our commitment to democratize access to physiologically relevant human models of neurodegenerative disease and make them widely available to the global scientific community.
Read the full press release here: https://axolbio.com/prism-als-new-stem-cell-models-could-transform-research-into-treatments-for-mnd-als/
