Artificial Intelligence
April 23–25, 2018
Boston, MA • United States

Day Two – Focus Group Wrap Ups

National Security Through Neurodevelopment: County Initiatives to Meet CNS Challenges
Neurodegenerative and neuropsychiatric diseases threaten the United States and wide swaths of the globe. Alzheimer’s disease (AD), alone — where 120 million across the world may be affected by mid-century — may cost trillions of dollars. The economic burden on families and governments will be tremendous and could lead to a global economic crisis over the next generation.

The demographic trends are clear: In western society, we have added a third to our lifespan and have low birthrates. As a result, we face a tsunami as the populations across the globe age. Until recently, AD, was a fairly rare disease, with the risk being 1 in 8 at age 65, but rising sharply to 1 in 2 at age 85. AD will be a common occurrence more and more in the future, as it correlates well with age.

But governments across the world have been slow to recognize this. NIH funding for AD was approximately $600 million last year. By comparison, HIV/AIDS spending was over $3 billion. To invest now in basic research will save the estimated $1.2 trillion Americans will be spending per year to care for AD in only 20 years. David Cameron’s call for a global fight on AD during the 2013 meeting of the G8 is a start. The UK’s $100 million Dementia Discovery Fund is another effort to develop collaborations between the public, private and non-profit sectors.

To heighten the alarm and call to action, we ought to stop looking at this just as a disease process, but rather as an economic crisis. WHO has issued a report on the coming pandemic. But where are reports from the World Bank or IMF? We should re-think spending on health and medical research not as a cost but as an investment — just as we did on a global scale with HIV/AIDS.

Due to stigma, there’s no public voice for mental illness as there is for other diseases. And for mental illness, the funding situation is even more critical. NIH spends far less on mental illness than other neurological conditions. Pharma is still investing in neuro, but it is getting out of R&D and drug discovery for psychiatry. This will obviously reduce the number of therapies in clinical trials and will drastically reduce the pipeline of young scientists entering the field.

Perhaps a paradigm shift in our thinking will help: AD is not as a disease of 80-year olds; it is a disease in its early stages of people in their 40s and 50s. Collaboration and leadership are needed from the political, corporate and NGO sectors to capitalize on this realization. After all, our collective cognitive health will equal our economic wealth.

Technology, Pathology, Radiology: Changing the Game through Neurodiagnostics
The promise in imaging lies in being able to detect disease through multiple modalities and thus, diagnose sooner and more accurately. In the past, neurological diseases were studied post-mortem, and we depended on lesions to show function and structural correlation. The shift has moved from first a gross level, then a cellular level, and now a molecular level – finding out which genes and proteins are altered to cause inflammation and tissue damage. Becoming more “micro” and using data analytics will be continuing trends. Today’s imagers and pathologists are excited about possibilities in wearable MR, and radioomics. The recent changes in WHO classification of brain tumors to add molecular properties shows the global shift of diagnostics towards a more personalized approach. Our techniques are getting smaller and data is getting bigger – a promising combination.

Autism and Neurodevelopment: Are Therapies Possible Today?
This session, moderated by Pulitzer Prize-winning journalist and author, and Director of the Project on Public Narrative at Harvard University, Ron Suskind, explained that, 20 years ago, his own son was diagnosed with autism, at a time when not much was known of this “Rainman” affliction. The diagnosis of autism has exponentially increased and is now largely a public health issue.

The panel focused on the hurdles the speakers collectively face studying autism. The majority, about 25% of severe autism disorders, does not have an obvious genetic defect. In fact, there may not be a relationship between what is seen clinically and genetically in autism. It was said that in autism, there are no treatments; therefore small improvements can be revolutionary. Measurements of outcomes in drug developments in autism research are also quite complex. Parent warriors are often scientists who were touched by autism in a personal way, as is directly seen on this panel. Social media has made broad-reaching clinical trials possible, connecting with other parent warriors from far and afield. Crowd source funding is also utilized.

A collective goal amongst the panelists is to better understand the molecular defect(s) of autism, and to determine a way to objectively measure outcomes of experimental treatment. One panelist offers the possibility to discover treatable idiopathic subtypes of autism. Perhaps inflammation plays a causal role in some subtypes of autism that can be targeted with effective therapies. Collectively grappling with the impressive and challenging future of autism research, it does not seem that any of these panelists are capable of limiting themselves in their pursuit to define, treat and end this disease. In the end, the moderator, Ron Suskind, Pulitzer Prize-winning journalist and author and Director of the Project on Public Narrative at Harvard University, also rallied for the societal inclusion of those already autism-afflicted, highlighting the strengths or passions of differently-abled people, while seeking creative adaptations and treatments to enhance their quality of life.

Pyschiatric Targets: Finally New Mechanisms
Today, most of us know – either as family members, friends or work associates – people who suffer from some form of psychiatric disease. Yet, the delivery of care and the corresponding investment in research, infrastructure, and medical support suffer from a disproportionate lack of resources, compared to other targeted health programs such as cancer. As was noted in the earlier session on neurostimulation, venture capital investment for psychiatric diseases is less than 10% of the cancer investment. Maurizio Fava, M.D., Executive Vice Chair, MGH Psychiatry and Slater Family Professor of Psychiatry at Harvard Medical School, added that the drug therapies available today (mostly monoamines) have been available for years, and very few new drugs have made it to Phase 3 trials. Other participants contributed their analyses about why the industry has not championed new therapies.

Deborah Dunsire, M.D., as CEO of FORUM Pharmaceuticals, stated “Show me the target.” Her assessment of the industry is that the therapies and outcomes lack the tools to successfully predict the risk of the investment. Fava commented that the placebo effect resulted in a number of Phase 3 trials being abandoned.
One theme was the need for better biological markers that can be used in providing more accurate and actionable diagnoses. David Silbersweig, Chairman, Psychiatry at BWH and Stanley Cobb Professor of Psychiatry at Harvard Medical School, in his opening comments, referred to the difficulty of working with patients where many of the symptoms are self-reported. He also pointed out how recent research has identified the high level of interaction between the executive functions and the limbic system – which makes some of the traditional categories less useful. Instead, he emphasized that new methods have explored the role of the environment along with current therapies. Part of this discussion was also the need for better metrics for outcomes.

Another theme was the emerging use of CBT (cognitive behavioral therapies). Corey McCann, M.D., Ph.D., Founder and CEO, Pear Therapeutics, discussed the approach his company has taken in merging software-based CBT technology with various drug therapies. The panel discussed the application of CBT to post traumatic stress disorder (PTSD) and the underlying mechanisms that deal with fear circuitry. CBT – using contemporary game technology – allows the patient to work through his or her fear experience so that the narrative can be selectively disassociated from the emotional response. PTSD has gained a lot of recent attention in the industry, partly because of the need to treat the veteran population. McCann stated that studies have shown that CBT plus an antidepressant have treated depression better than either one alone. It also has the benefit of working with several existing drugs, and it can be deployed for new indications without some of the overhead currently associated with FDA approval of new drugs.
Other topics covered included addiction, active and passive monitoring using cell phone technology, and imaging. The panel was generally upbeat about the future.

Sleep and Consciousness: Clinical Need Versus Safety
Sleep serves as the bedrock of good health. And poor sleep, either in duration, quality or continuity, may have significant negative implications for overall health.

While we sleep, parts of our brain are quite active. Deep, slow-wave sleep at the beginning of a sleep cycle helps to consolidate memory, while REM stage sleep that occurs much later in the sleep cycle helps us integrate what we have learned. REM sleep assists with the development of insight and understanding. And when we are asleep, the brain’s own drainage system removes harmful metabolites like amyloid beta.

A number of factors get in the way of sleep. Many of us are over-caffeinated and spend too much time in front of TV and other device screens. The light emitted by these devices interferes with the normal role of melatonin and delays the onset of sleep. Millions of others, many unaware, suffer from interrupted breathing during sleep – sleep apnea. Still others face chronic disorders of insomnia and narcolepsy. Chronic pain and psychiatric illnesses can also disrupt sleep.

Research is needed to identify biomarkers so that personalized therapies can be developed. Intensive effort and significant resources will be needed to see if it is possible to come up with a blood test to indicate who among us is at greater risk for a given sleep disorder. It was once thought that all sleep apnea, for example, was the same. Research has shown there to be a number of subtypes. Continued work to indentify subtypes will help develop more effective therapies.

Many of the wearable computing devices like Fitbit and sleep monitors are generating great interest. As more and more individuals are collecting data, including on sleep habits, patterns are emerging. This data may also be used for diagnostic and treatment purposes. However, these devices are early prototypes and as such, can produce erroneous data or even be “tricked” into producing false results. As they become more sophisticated, they may be able to offer more insight into sleep and other health indicators.

Exciting new areas to be explored include the genetics of sleep pathology. This coincides with the groundswell of interest in personalized medicine.

Parkinson’s: Finally Crossing the Therapeutic Threshold
The first part of this panel focused on the need for better biological markers which would result in enhanced diagnostic capability, and the second part dived into current therapies for Parkinson’s disease. Michael Schwarzchild, M.D. Ph.D., Chair, Parkinson Study Group Executive Committee at MassGeneral Institute for Neurodegenerative Disease, and Professor Neurology, Harvard Medical School, opened the session by providing an overview of what Parkinson’s is and its prevalence in the population (second most common disease behind Alzheimer’s). He also reviewed some of the recent findings, particularly in the emergence of some of the genetic clues and their complex interactions with environmental factors. New insights have been gained on the progress of the disease and early diagnosis. He stressed that the most typical symptom of Parkinson’s – tremors and other motor disorders – is not necessarily the first manifestation of the disease (for example, sleep disorders, depression, etc.) As he remarked later in the session, there is still no unifying hypothesis for Parkinson’s.
The difficulty in identifying biomarkers was complicated by the effect of patients already in treatment. Some studies have taken 10 years and have been very costly. Clemens Scherzer, M.D., Director, Neurogenomics Lab and Parkinson Personalized Medicine Program, Brigham and Women’s Hospital/Massachusetts General Hospital, and Associate Professor of Neurology, Harvard Medical School, described the collaborative approach his team has taken at Harvard and the positive results they have achieved. Results are now measured in weeks rather than years. Todd Sherer, CEO of the Michael J. Fox Foundation, also championed collaborative research and described some successful programs they have run. So far, the strongest markers have been genetic.

Current therapies seem to be centered on the continued use of dopamine-based strategies. Scherzer noted that of 35 recent trials, only a handful include disease-modifying drugs. The improvements are more focused on better delivery mechanisms, so that a patient can gain relief in a matter of minutes rather than in 30 to 40 minutes (based on inhalationm versus oral intake). More work is also being done on integrating non-motor symptoms into the treatment portfolio.

New Leaders at the Table: Filling the Gap Through Philanthropy
Henry McCance, dynamic speaker and Co-Founder of Cure Alzheimer’s Fund eloquently defined this nonprofit organization, founded in 2004, by several families who were frustrated by the slow pace of research. This fund is a new venture-based entity created to speed research and exclusively focus on finding a cure, leveraging successful returns that de-risk research and thus become more attractive to public funding sources.
Meryl Comer, President of the Geoffrey Beene Foundation’s Alzheimer’s Initiative, spoke of her role as long-term caregiver of her afflicted husband and her realization that she needed to turn the suffering into purpose. Comer spoke of actively changing the direction and pace of medical research, by mining public databases, or “big data,” and not focusing on reinventing the wheel, as well as utilizing collaborative technologies to help foster data collection and analysis. The Initiative has generated more than $4.8 million so far, in support of awareness programs and early diagnostic and treatment research.

Nancy Frates, mother of Pete Frates, described how their family enveloped themselves in philanthropic relationships that banded together to amplify funding for ALS research. A fellow ALS sufferer came across the Ice Bucket Challenge and brought it to Pete’s attention, and the Frates family quickly and efficiently used social media to use the Challenge to spread the word, as well as to raise the funds to be proactive and accelerate ALS research.
CEO of Forma Therapeutics, Steven Tregay, spoke of how Forma is helping to transform the drug discovery process through collaborations in pharma.

Jeff Walker, Vice Chair, United Nations Envoy Office of Health and Finance and Malaria, shared that he just lost his father t Alzheimer’s last Friday. He spoke of pointing out to investors that their investment “return” is invaluable.
Bill Sahlman, Senior Associate Dean of Harvard Business School, brilliantly defines the biggest “data dumps: on everyone’s hips, the cell phone. The importance of gathering information on a big scale is very important, and cell phones are ideally placed for this purpose. He does not feel that privacy concerns should get in the way of utilizing these ubiquitous tools for research purposes.

The takeaway message of this panel was that in an age where we are living longer lives, it may be that it’s not if you get Alzheimer’s, it’s when, and we should all be active investors in its prevention, treatment and cure.

Posted by Jim Coburn, Christine Dyer-Ward, John Hannigan and Fares Nigim