Advancing Discovery: We Need A Mars Shot
Oct 24, 2016 - 3:02:06 PM
But for advancing knowledge in the field of mental illness, we need something more like a “Mars shot,” because no one has ever been to Mars before. Currently, we don’t know why we get mental illnesses. We think it has something to do with connectivity in the brain, but there are no easily detected biomarkers – no diagnostic blood tests, no scans, no definitive genetic tests - that tell a doctor that the patient has depression, bipolar disorder or schizophrenia. Yet those illnesses are very real and deserve the same attention and the same breakthroughs that we are seeing in so many other areas of medicine.
The National Alliance on Mental Illness (NAMI) has looked at a wide array of other health care conditions and their timelines and pipelines for new discoveries. For example, there has been a profound increase in the life expectancy for HIV-infected individuals due to progress in understanding the virus and designing effective treatments for it. Some cancers have known genetic dimensions that are now informing treatment choices. Even for brain disorders such as Alzheimer’s Disease, active research into biomarkers is underway that could result in new treatments. These are exciting developments. Comparatively, discovery in the treatment of mental illness is not moving nearly as quickly. We have simply not seen the same scientific advances in understanding the underlying neurobiology of these conditions.
It’s worth taking a moment to consider why there is this disparity in innovation for brain disorders. There have been no fundamentally new therapies for psychiatric disorders for 50 years – the incremental advances in improving the drugs’ tolerability and side effects are welcome and necessary, but we desperately need new treatments too. Many pharmaceutical companies, however, have retreated from investing new therapeutics for CNS disorders in recent years. This is because the likelihood of failure is incredibly high – much higher than for other disease areas, and mostly for reasons of lack of efficacy. Why is this? One reason is because there are noanimal models of psychiatric disease that are based on disease mechanism. This is partly because animal models are inherently difficult to get right for diseases of the human brain. The pre-frontal cortex is vanishingly small in rodents, thus the circuits that are affected in humans are not even present in a mouse.
Secondly, disease mechanisms are lacking. As noted above, without biomarkers that provide a biological readout of disease, there is very little that can be measured in an unbiased way in research studies. Finally, the inaccessibility of the human brain during life limits the ability of researchers to examine patient tissue during, or prior to, the onset of disease. Post mortem studies are difficult to design and also require a detective approach to discern what may have caused the disease decades earlier, rather than what is a result of it. These barriers are not insurmountable, but they are significant. It is clear that investment is needed to find ways around the scientific hurdles, and a coordinated re-engagement of pharmaceutical companies so that new insights can be harnessed with no unnecessary lag-time.
All this means that lots of individuals living with mental health conditions, and the concerns of those who love them are being “left behind” relative to other diseases because current drug therapies are often unable to help manage symptoms. Additionally, current antipsychotic medications carry a significant side effect burden. Weight gain, early onset of diabetes and movement disorders like tardive dyskinesia present significant risks. NAMI’s HelpLine at times takes heart-breaking calls around such issues; a therapy may be working well in addressing a person’s symptoms, while side-effects make the person miserable.
We in the mental health community have a lot of experience with getting left behind. That’s one reason we are still fighting for mental health insurance parity. We are the only ones who were told: “You can only be in the hospital for 20 days.” That kind of restriction just doesn’t happen for other health care conditions—but it is the reality when a patient is admitted, and then quickly discharged, for mental health. We don’t want to see research innovation bypass mental health as well. We need bold innovation in treatments and services that work.
To address these issues, last month, NAMI partnered with the Stanley Center for Psychiatric Research at the Broad Institute, an academic collaboration between Harvard and MIT and a major force in genetic research for mental health conditions. Together, we invited leaders from the National Institute of Mental Health (NIMH) and the Substance Abuse and Mental Health Services Administration (SAMHSA), representatives from the pharmaceutical industry, faculty from the Stanley Center, consumers and families to ask: How do we get better, more effective therapeutic medications, particularly around psychotic illnesses? More specifically, what would it take to “de-risk” investment in schizophrenia? Because of recent developments surrounding schizophrenia—including the RAISE study and genetic findings from a large global collaborative network anchored by the Broad Institute—this is a timely question for that illness. So we started there.
We began simply by inviting key stakeholders into a room together to have conversations that we hope will grow to larger and more impactful discussions and actions. We were moved by the alacrity with which all our guests accepted the invitation. There is clearly great energy and motivation by all stakeholders to move the dial on this issue, and it’s up to all of us to find ways to collaborate. In convening this group, we have built upon work done by other pioneers such as One Mind, which has been investing resources and advocating to improve collaboration in mental health research for many years. We believe that with a clear direction and a lot of open dialogue, collaboration and trust, we can take the next step forward.
The Advancing Discovery Summit certainly fulfilled our expectations of a great ice-breaker between the many groups that came together for the day. There was a willingness from all parties to lay aside differences to focus on what we all shared: a commitment to advancing knowledge of severe mental illness in a way that informs new and better treatments. There was much discussion of the “ecosystem” that exists in mental illness research, and the many and varied ways we need to promote the health of that ecosystem, to move forward on the path to successful treatment. The consensus at the end of the day of discussion was that whatever our next step may be, we should be bold in our aims. There was also an agreement that we should not lose the momentum from this rich discussion, and we at NAMI and the Stanley Center commit to keeping the conversations going to ensure we meet our goal. We also acknowledged that this first meeting (necessarily) did not include all parties who should be engaged in future, including stakeholders from the legal and financial sectors and greater representation from academia well beyond the Stanley Center.
There was much hard work behind the scenes in organizing the summit. We thank members of the steering committee, Reos Partners for their facilitation and staff from NAMI and the Stanley Center. We thank Alkermes, Eli Lilly & Co. Johnson & Johnson and Otsuka for their participation on the steering committee and helping to sponsor the discussion. We are thankful for a generous gift from the Breuer Family. We also greatly appreciated the visit of the new NIMH director, Dr. Joshua Gordon, who affirmed the goals of the summit and NIMH’s long-time commitment to NAMI as a partner.
The day gave us a lot of hope. We hope it will to you as well. It is an exciting time for scientific advancement and inspiring to know that individuals and families affected by mental illness are not alone on their journey. We will be producing a paper and video from the day and look forward to sharing them and our next steps with you as we go along.
It’s a long way to Mars, but this is a journey we need to begin.
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