How Biomarkers Can Inform PMS Therapy Development
Recently, biomarker development has been mentioned a lot in the neurodevelopmental disease community, but it's often unclear to patient families what researchers are exactly trying to accomplish and how this will benefit patients. Here, I'll try to explain some basic biomarker concepts that are relevant to PMS families.
What Is a Biomarker?
Biomarkers are measurable indicators of a biological condition. They are often measured in body fluids, such as blood or urine. Commonly used diagnostic and monitoring biomarkers can tell us about certain disease conditions, such as a blood test to check liver function, or blood sugar levels to monitor diabetes. Another common biomarker is blood pressure, which can be used to predict the risk of a future heart attack or stroke.
Why PMS Research Needs a Different Kind of Biomarker
For neurodevelopmental diseases like PMS, a different kind of biomarker is being investigated: biomarkers related to therapeutic outcomes in clinical trials. Families are familiar with periodic assessment tools used to describe a patient's disease symptoms and general skills and abilities. This is done through observational tests at the doctor's office and through well-established questionnaires filled out collaboratively by caregivers and doctors. Unfortunately, these tools are often not optimal for measuring the impact of therapies in a clinical trial quickly, precisely, and objectively. Results may vary depending on how the patient is feeling at the time of assessment, and whether assessors are biased regarding treatment status (even in a blinded trial, parents may be able to tell whether their child is receiving the study medication or a placebo).
Regulatory authorities such as the FDA have been urging clinical researchers to develop clinical trial biomarkers that can be precisely measured without possible bias. There has been some progress in neurodegenerative diseases, where brain-imaging-based and cerebrospinal-fluid-based biomarkers are now used in the clinic to assess how well treatment preserves brain cells. For neurodevelopmental diseases, we still have a long way to go, and CureSHANK is actively engaging with experts to find and test possible approaches.
The Challenge of Blood-Based Biomarkers for Disorders of the Brain
Blood-based biomarkers for disorders of the brain will be difficult to interpret, since they don't directly inform us about how a therapy affects the brain. For example, measuring SHANK3 protein levels in blood cells may be helpful for monitoring certain treatments, but this approach likely wouldn't be acceptable to the FDA as measurement of the drug’s impact in the brain.
Looking to EEG and Other Emerging Approaches for PMS
CureSHANK is currently evaluating other potentially promising biomarker approaches, such as EEG, which can directly measure brain activity. Researchers are still working to define which EEG changes are characteristic of PMS, and whether these changes are expected to be affected by therapies and could reliably be assessed in a treatment setting. An important consideration is that children's brains are still developing with naturally changing EEG patterns—this could complicate usefulness in a clinical trial. There are other interesting, non-invasive measurements emerging, such as eye tracking and heart rate patterns during brain-dependent tasks.
The Path Forward
Developing any treatment outcome biomarker for PMS will take a long time and require close collaboration between patient families, clinicians, and therapeutic companies. The stakes are high: EEG, for example, is still under-researched in PMS, yet may offer novel insights into disease and therapeutic mechanisms. Objective, accurate and easy-to-measure biomarkers could greatly improve the efficiency of clinical trials, accelerate therapeutic development, and bring effective new treatments to patients faster.
Ralf Schmid is the Chief Scientific Officer (CSO) at CureSHANK and can be reached at research@cureshank.org
