A lack of reliable blood-based biomarkers is one of the biggest challenges facing ALS researchers and clinicians. Better biomarkers for the disease could help make diagnosis faster and enable faster, more reliable clinical trials. Discovering new biomarkers is one of the key goals of the ALS Therapy Development Institute’s (ALS TDI) ALS Research Collaborative (ARC) Study.

To further power our search for ALS biomarkers, ALS TDI recently announced a new partnership with LifeArc, one of the United Kingdom’s leading charitable biomedical research organizations. LifeArc will provide funding to support biomarker research at ALS TDI, while also lending their expertise as a collaborator to analyze these data and help advance new ALS biomarkers toward use in the clinic.

Who is LifeArc?

LifeArc is a UK based self-funded, not-for-profit medical research organisation and charity. For over 25 years, it has been advancing translation of early science into health care treatments or diagnostics that can be fully developed and made available to patients. This has resulted in five licensed medicines including Pembrolizumab, sold under the brand name Keytruda, a humanized antibody used in cancer immunotherapy.  LifeArc’s success allows it to reinvest the proceeds from the drugs they have developed to support promising research at other organisations

Part of LifeArc’s mission is to support research in diseases with unmet need, including ALS, or Motor Neuron Disease (MND), as it is referred to in Europe. They have funded a number of research initiatives in Europe through their MND Translational Challenge program. This new collaboration with ALS TDI represents their first partnership for LifeArc’s MND Translational Challenge with an American organization.

“LifeArc is really thoughtful about the research that they choose to focus on,” says Dr. Fernando Vieira, CEO and Chief Scientific Officer of ALS TDI. “I’m proud that they've chosen to work with ALS TDI. I think that the two organizations are kindred spirits in a lot of ways, both being nonprofits that have our own research capabilities. There's a mutual understanding of the type of work that needs to be done to get to solid answers. I believe they’ve been encouraged by the quality of work that we’ve done over the years and the resources that we have to make a dent in ALS/MND.”

Finding New Biomarkers 

Since 2014, the ARC Study has collected thousands of blood samples from people with ALS. ARC researchers have analyzed the levels of approximately 7500 different proteins in many of these samples – work that has been supported in part by a grant from the Department of Defense’s Congressionally Directed Medical Research Program (CDMRP). For this collaboration, LifeArc will work with ALS TDI researchers to further analyze these data. Utilizing LifeArc’s expertise in advanced statistical analyses and machine learning techniques, they will look for patterns in how these proteins behave in samples from different individuals. If these patterns appear to correlate with different rates of progression, symptom severity, or other aspects of the disease, the protein in question may have potential to serve as an ALS biomarker.

Validating Potential Biomarkers

Once a potential biomarker has been discovered, it must be validated. This means that researchers need to provide adequate evidence that it is a reliable and accurate measure to secure approval from regulatory authorities like the FDA.

  • For a biomarker meant for diagnosis (a diagnostic biomarker), researchers need to gather data from large populations both with the disease in question and other, similar diseases to demonstrate that it will not result in misdiagnosis.
  • For a biomarker meant to measure disease progression or symptom severity (a prognostic biomarker), researchers need to show that levels of that biomarker consistently lead to accurate predictions, often across multiple datasets. In addition, they must show that the tests they have developed to measure the biomarker are also reliable.

For this project, LifeArc will provide funding to support experiments at ALS TDI to validate two potential biomarkers – TIMP1 and MMP9­ – that have been highlighted through the ARC Study. If any additional proteins are discovered through the analysis of past ARC samples, they will also be investigated as part of this program. While the general search for new potential biomarkers will occur in ARC’s archive of previously collected samples, these more detailed analyses will be conducted in new blood samples from current participants. This will allow ALS TDI and LifeArc researchers to closely track the behavior of these proteins over time in different individuals.

“This project is the logical continuation of our ARC efforts,” says Dr. Vieira. “First, we're leveraging data that we've already generated through ARC from samples that we've collected over many years, to look at them in a different way and maybe to reveal new insights that we alone can't reveal. Then, we’re using new samples that we’re generating right now to do a higher-resolution analysis of specific markers that we already have flagged as interesting. We've used earlier samples to find things that have potential. Now, we're using the new samples that people are continuing to contribute to better understand what we’ve found.”

Bringing a New Biomarker to the Clinic

Once a biomarker has been validated and approved by a regulatory agency, clinicians and researchers need a way to test for it in their patients. A testing kit, such as a plate with antibodies that can detect levels of a particular protein in a blood sample, needs to be developed and manufactured at scale. This is where the final aspect of ALS TDI’s collaboration with LifeArc will come into play. If any of the proteins identified can be validated as ALS biomarkers, LifeArc can provide the R&D and manufacturing resources to develop a test that can be produced and distributed to ALS research labs and clinics.

Paul Wright, Head of the MND Translational Challenge at LifeArc said "We are thrilled to collaborate with ALS TDI, an organization that shares LifeArc's commitment to putting patients at the heart of everything we do. Together, we aim to advance crucial research in the search for new ALS biomarkers, a key step towards better understanding and treating this devastating condition. This partnership goes beyond funding; we are bringing our expertise in early translational science to help support their research, and hopefully together, we can progress discoveries that have a meaningful impact on the lives of those affected by ALS."

This project, which was first announced in May, 2024, is currently underway, with the goal of concluding the lab work portion at ALS TDI by the end of 2025. To follow the progress of this collaboration and ALS TDI’s many other research projects to end ALS, subscribe to our newsletter.

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