What if we started diagnosing brain disorders based on physiological measures as opposed to the behavioral measures that are currently in use now? This is the provocative question that kicked off the five-person panel discussion at the sixth annual Partnering for Cures, moderated by Kafui Dzirasa of Duke University Medical Center.
When someone presents in the emergency room with chest pain, an electrocardiogram (EKG or ECG) will most likely be used to assess the electrical activity of that person’s heart, and information about the heart’s function will be gleaned from that test – in essence, a physiological measure. When asked about opportunities to begin diagnosing brain disorders based on physiological factors,Magali Haas of Orion Bionetworks made it clear that in order for that to happen, one has to start defining brain disorders based on the underlying molecular biology that defines them. Deborah Dunsire of FORUM Pharmaceuticals echoed Haas’ sentiment and went further to describe how such information could affect drug development for brain disorders by stating that “…the great advantage of having that information would be to be able to target the drug more specifically to specific altercations and connect that physiological driver to the altercation that changes it.”
However, before we can even get to that degree of specificity within brain disorder therapeutics, we have to address the gaps in our understanding of the biology of the brain. Allan Jones of the Allen Institute for Brain Science described how work undertaken at the Allen Institute is working toward understanding brain architecture, at both the cellular and functional level. Jones gave the startling example that the average brain has about 85 billion neurons (a type of brain cell). We don’t really know how many types of neurons there are within that group or how those neuronal types function within a circuit in a normal human brain and in a diseased human brain. Dzirasa pointed out that this sort of initiative will require a different type of scientific approach, which Jones has referred to as “big science” – science being done in an orchestrated way, on a larger scale, with crisp and clear objectives. Jones’ idea of “big science” draws similar parallels to systems biology-integrated approaches to addressing brain disorders, which was a theme throughout the panel discussion.
Further emerging from the conversation was the idea that we need to build new frameworks to ask different types of questions. Meryl Comer of The Geoffrey Beene Foundation Alzheimer’s Initiative and WomenAgainstAlzheimer’s ran with that idea, stating that we need to “change the type of energy” surrounding our approach to brain disorders. Her organization launches innovation challenges to tackle big issues; she feels that by mobilizing and empowering “a new type of investigator,” such as citizen scientists and caregivers, we can inform the science and approach disease-modifying therapies faster.
Moving onto the question of treatment versus prevention, Reisa Sperling of Brigham and Women’s Hospital and Harvard Medical School made it clear that detecting early brain changes that lead to brain disorders, namely Alzheimer’s disease (AD), is imperative. Now that the technology exists to detect amyloid plaques and tangles (one of the main changes that happens in an AD-affected brain) in living people, it has been found that more than one-third of adults over the age of 65 has evidence of these plaques and tangles. However, as Sperling pointed out, questions still remain about whether those folks will indeed get AD, and more importantly, whether we can do something about it. Haas suggested that we need to build prediction tools that integrate multiple nodes of information, such as functional brain imaging, blood work, and cerebrospinal fluid sampling to tackle those questions.
Highlighting some of the barriers to tackling brain disorders, Jones pointed out that there is a cultural barrier in science of hoarding data, which needs to transition into more sharing and collaboration. To further that point, Haas believes that “we need to have a unified voice,” indicating that we may be too siloed in this space. She pointed out that there are more than 600 diseases of the brain, yet brain diseases are typically discussed as individual diseases, which may dilute advocates’ voices when they approach policymakers and funding agencies. Funding was another issue raised, as Sperling stated that “we need to make some major investment in the brain sciences… in basic research, translational, and clinical research within the next five years.”
In closing, Dzirasa asked the panel how we actually approach the existing barriers and push toward unlocking the mysteries of the human brain. Several ideas were advanced, from using public data to build prediction models, to funding from both the public and private sector, to data sharing. Among all the ideas, the whole panel underscored that collaboration is the key.