Earlier this year, pharmaceutical giant AstraZeneca announced it was ceasing drug-discovery research for psychiatric disorders such as depression and schizophrenia. The move, along with cutbacks at other companies, has raised concerns about where the next generation of neuropsychiatric drugs will come from—see this Friday's issue of Science for a feature article exploring this topic.
Yesterday, ScienceInsider spoke with neuroscientist Menelas Pangalos, who in May took over as AstraZeneca's head of drug-discovery research and early development. His comments have been edited for brevity.
Q: What do the recent changes mean for neuroscience research at AstraZeneca?
M.P.: Basically, from a research perspective, we're pulling out of the psychiatry space. We're still very much focused on neurology, so Alzheimer's disease, pain, cognition, ... those areas are still very active.
Q: What makes research on psychiatric drugs less attractive?
M.P.: Our understanding of disease pathophysiology is still relatively in its infancy.
These are complex and heterogeneous disorders. Also, the size and robustness of the clinical trials made it a less attractive area for us to be in compared to other areas we were working in. There has to be a much better alignment between preclinical and clinical work.
Q: How so?
M.P.: In neurology, if you take stroke as an example, preclinical models of stroke tend to be occlusion of the middle cerebral artery, which causes ischemic damage in the brain of a rodent or nonhuman primate that mirrors fairly well what happens in the human situation.
When you start getting into psychiatry, we have tail suspension assays, we have forced swim assays, we have learned helplessness assays ... none of which have been developed through a detailed understanding of the pathophysiology. [In these tests, researchers measure how long it takes a rodent to stop struggling after being suspended by its tail or placed in a pool of liquid; giving up is presumed to be a rodent version of despair.]
Q: Aside from better animal models, what else is needed?
M.P.: We need better clinical development. We need to be able to conduct better clinical trials and understand which patients are most likely to benefit from our drugs.
Q: Are there any models out there for how to do that?
M.P.: The stuff that's been happening with ADNI [the Alzheimer's Disease Neuroimaging Initiative, funded by industry and the National Institutes of Health] is very important. Groups of academics and pharmaceutical scientists and clinicians are getting together and really trying to understand how to measure the disease, what the biomarkers might be, how it progresses, how many patients you need [in a clinical trial]. Those are the sorts of things that are really helping us in the industry and can ultimately make drug development more effective. ADNI has been a really great example of a precompetitive public-private partnership. We haven't had that yet in psychiatry.