First Project Mosaic initiative: Developing patient-specific models
Pilot project aims to lay foundation for precision medicine in ALS
In a new initiative, Mosaic Neuroscience is teaming up with Ixcells Biotechnologies to develop patient-specific cell models that could lay the foundation for advancing precision medicine in amyotrophic lateral sclerosis (ALS).
The pilot project is the first to be launched as part of Project Mosaic, an effort — backed by a group of nonprofits and industry stakeholders — that seeks to improve the development of ALS therapies by creating preclinical models that more accurately reflect the disease’s complexity and diversity.
“These models will give us a path to develop precision therapies for the majority of patients,” Bernie Zipprich, Mosaic’s founder and CEO, said in a company press release. “We’re thrilled to be partnering with Ixcells to take the first steps in this critical journey.”
ALS is a neurodegenerative disease in which the nerve cells that control voluntary movements are progressively lost. While the cause of ALS can be traced to specific genetic mutations inherited in families for a small subset, the majority of cases — about 90% — are sporadic and without a known cause. For these individuals, the disease is believed to arise from a combination of genetic and environmental factors.
Nearly all sporadic ALS therapies fail in development pipeline
Researchers point to a critical need for therapies that can effectively slow ALS disease progression. However, about 99% of sporadic ALS treatment candidates fail at some point in the development pipeline.
Zipprich, diagnosed with ALS in 2020 at age 32, launched Mosaic Neuroscience and its flagship initiative, Project Mosaic, to address this high rate of clinical trial failures.
Before new therapies can be tested in clinical trials, they have to first be tested in cell and animal models. Those involved in Project Mosaic believe that the models now available fail to capture the complexity of sporadic ALS, which contributes to clinical trial failures.
The clinical and cellular features of sporadic ALS vary widely, and more than 50 different genes have been linked to the condition. Current models don’t take that into account, so the investigational therapies tested in those models won’t end up working for most patients, the researchers note.
“The vast majority of ALS patients have the sporadic form of the disease, but nearly all of our preclinical tools are based on the familial forms,” said Eugene Brandon, PhD, Mosaic’s chief scientific officer.
The scientist said that using familial ALS models to develop therapies for sporadic ALS would be like using breast cancer cells to find treatments for liver cancer — they don’t have enough in common for it to make sense.
Project Mosaic’s goal is to develop better preclinical models that recognize ALS not as a single disease, but rather as several overlapping subtypes that share common characteristics. Therefore, precision approaches that account for this diversity are needed to better treat ALS patients, according to the Project Mosaic website.
To accomplish that, the group is turning to methods used in cancer research, where therapies are commonly tested in cells from individual patients before entering clinical trials.
Project Mosaic aims to speed industry adoption of academic discoveries
However, because ALS is a neurological condition, and it isn’t possible to collect a brain tissue sample from patients, Project Mosaic is working on developing so-called neurobiopsies. These are lab-grown nerve cells generated from the stem cells of individual ALS patients that then reflect their specific disease characteristics.
In the pilot project with Ixcells, the scientists will use patient-derived stem cell lines from Answer ALS to identify unique gene activity profiles representative of sporadic ALS. Later, the researchers will assess how these patterns can be used to match patients to appropriate medications.
By working with industry partners like Ixcells, Project Mosaic aims to shorten the amount of time it typically takes for discoveries in academic settings to be adopted by industry partners and lead to meaningful change for patients.
“What excites us about Project Mosaic is not just the urgency – it’s the rigor,” said Nianwei Lin, PhD, president and chief scientific officer of Ixcells. “It’s a systematic effort to make [sporadic ALS] disease models a new preclinical standard.”
[Project Mosiac’s approach is focused on] fixing the broken ALS pipeline — at the speed this disease requires. … This can only happen if ALS nonprofits, academic researchers, and industry work together in new ways.
After the pilot finishes, Ixcells will make sporadic ALS models that researchers and pharmaceutical companies can use, along with artificial intelligence models and other patient-specific data, to develop precision medicines for sporadic ALS. Project Mosaic will then bring other collaborators on board to further validate the pilot results.
According to Zipprich, the approach is focused on “fixing the broken ALS pipeline — at the speed this disease requires.”
“This can only happen if ALS nonprofits, academic researchers, and industry work together in new ways,” Zipprich said. “Someone new is diagnosed every 90 minutes and people are dying every day. We have no time to waste.”
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