John leads a team of scientists who work on discovering and applying biomarkers in drug development to help identify patients who are most likely to respond to treatment and determine the best dose and biological effects of the drug. Today, these measurements are most frequently acquired through imaging or cerebral spinal fluid (CSF), which have been instrumental in propelling neuroscience research forward. But they still have limitations.
Advanced imaging equipment is expensive and typically only available in large, affluent geographic areas with sophisticated, local medical infrastructure. CSF technologies typically can be centralized since biosamples can be rapidly transported, but the process of acquiring the sample is more invasive because a trained neurologist must perform a lumbar puncture, and the patient may require anesthesia.
Testing for biomarkers in blood samples, on the other hand, is a well-established paradigm in medicine in every culture. However, whereas blood samples are easy to acquire and can be readily transported, the concentration of biomarkers that are related to the brain is very low in the blood. Additionally, they are affected by other processes in the body, for example, our kidneys or liver clearing proteins from our blood.
“We are now seeing the emergence of ultra-sensitive technologies that can reliably detect, and in some instances even quantify, brain biomarkers in blood samples, including pathological amyloid and tau in Alzheimer’s,” says John.
The impact of this capability is significant for drug development in neurology. “If we can detect a given brain biomarker in a blood sample, we can get biomarker measurements from every single patient enrolled in our trials, not just a subset with easy access to imaging or lumbar puncture capabilities. We can also pull blood samples when patients come in for monthly drug infusions, enabling us to see how biomarkers are changing month by month instead of just the typical one or two times following treatment. This, combined with imaging and CSF could potentially help us optimize dosing regimens and potentially shorten clinical trials, ultimately getting better treatments to patients faster.”
Imaging, John says, provides a window into the patient’s history, for example, showing long-term damage in the brain, while CSF and blood provide a snapshot of the patient’s current state.