The Hopeful Future of Precision Medicine

Many of us have experienced the pitfalls of a “one-size-fits” all approach to medicine, where physicians prescribe treatment for the “average patient” instead of the one sitting in front of them. By not accounting for the variability in genes, environment, and lifestyle that are often so closely tied to health and illness, treatments end up falling short and sometimes do more harm than good. Fortunately, the “precision medicine” movement, which takes into account the patient’s unique characteristics when prescribing treatment and prevention strategies, has gained traction in recent years.

In 2015, President Obama funded the Precision Medicine Initiative to ensure that researchers could focus on creating efficient and effective ways to integrate more personalized treatment plans into the current healthcare and medical system. This year, we’re excited to have some of the front-runners in the precision medicine movement on the TEDMED stage!

Photo credit: Bryce Vickmark. Image provided by PanTher Therapeutics.

Photo credit: Bryce Vickmark. Image provided by PanTher Therapeutics.

An immediate goal of the Precision Medicine Initiative is to apply this approach to catalyze cancer research. While we have learned more about cancer prevention, detection, and treatment in the past 2 decades than we have learned in the previous centuries, we still haven’t found a treatment that doesn’t harm the patient in the process. The TEDMED 2016 Hive company PanTher Therapeutics is working to change this. As their CEO Laura Indolfi puts it, “it seems very counterintuitive to have a whole body treatment to target a specific organ.” The company is studying the precise delivery of existing, already proven chemotherapy agents directly onto the tumor using flexible plastic patches for consistent, slow release over time. PanTher is completing pre-clinical testing prior to initiating human trials for patients with pancreatic cancer, but hope to apply the same technique to treat other forms of cancer in the near future.

Another goal of the Precision Medicine Initiative is to harness the power of data to highlight trends about disease and health, in search of more effective treatments. This is precisely what Andrew A. Radin and his team at twoXAR are working on. The TEDMED Hive organization has produced efficacy signals in preclinical studies in multiple diseases. To date, twoXAR has completed over 75 disease prediction models and has 9 drug discovery collaborations, including both rare and common conditions.

Ultimately, the Precision Medicine Initiative aims to translate this method of prevention, treatment and care across all fields of health and healthcare. One area where precision medicine could have a measurable impact is in the study of neurodegenerative diseases, due to the relationship between genetics and neurodegenerative disease. The TEDMED 2016 Hive organization Denali Therapeutics is researching the genetic causes and biological processes underlying neurodegenerative disease and using this information to create targeted treatments for Alzheimer’s disease, Parkinson’s disease, ALS and other neurodegenerative diseases. Led by Chief Medical Officer, Carole Ho, Denali’s research team has identified multiple drug targets that could lead to breakthroughs in the treatment of Parkinson’s and Alzheimer’s disease.

TEDMED 2016 Hive organization Frequency Therapeutics is looking to uncover the body’s hidden biological potential to heal itself. Led by Co-Founder, President and CEO, David Lucchino, Frequency Therapeutics is developing small molecule drugs that activate progenitor cells within the body to restore healthy tissue in a precise and controlled way. With recent discoveries in stem and progenitor cell biology, Frequency Therapeutics is creating therapies that could reverse sensory hearing loss by targeting specific hair cells within the inner ear. Their approach is promising not just for the almost 1 billion people across the world who are affected by hearing loss, but for the potentially large impact on other diseases as well.

Image provided by Charles Chiu.

Image provided by Charles Chiu.

Using the precision medicine approach would also enable us to prevent the spread of disease much more efficiently. With the recent Ebola and Zika outbreaks, many are wondering how we can stop the spread of similar outbreaks in the future. Charles Chiu, an infectious disease physician and researcher, is pioneering the clinical implementation of a tiny next-generation sequencing device from Oxford Nanopore Technologies that could drastically change the way we respond to the next deadly bug. This device “can detect all pathogens – virus, bacteria, fungus, parasite known or unknown – in a single test,” says Chiu, and can do so in a matter of hours and in remote, low-resource settings. By using this device, we could decrease the time it takes to find diagnoses, which would help curb the spread of outbreaks and enable clinicians to provide timely and effective treatments for their patients.

Thanks to these extraordinary innovations, the future is looking brighter already. From preventing pandemics; to defeating neurodegenerative diseases; to curing and preventing hearing loss; to accelerating drug discovery; and creating a new therapy for cancer, each of these TEDMED Speakers and Hive innovators are working to ensure that the goals laid out in the Precision Medicine Initiative become a reality for generations to come.

With these exciting breakthroughs just around the corner, we are excited to hear more about these inspiring innovations as these Speakers and Hive entrepreneurs take the stage at TEDMED 2016. Register today to join us in Palm Springs, CA, this November 30 – December 2.

Making Connections Through Data

Lori Melichar photoLori Melichar is a director at the Robert Wood Johnson Foundation—the largest philanthropy in the United States dedicated solely to health and health carewhere she focuses on discovering, exploring and learning from cutting edge ideas with the potential to help create a Culture of Health. She can be found on Twitter @lorimelichar.

Data about us—where we are, what we’re buying, what we’re reading—is being collected everyday, everywhere. Our cell phones, TVs, wearables, watches and even our Facebook feeds collect data about our daily lives. The Robert Wood Johnson Foundation (RWJF) is convinced this data also contains important insights into how we live, learn, work and play—and we think harnessing these insights could lead to major improvements in the health of all Americans.

Efforts to make sense of all this personal data and unlock the knowledge within are underway.

RWJF grantee Health Data Exploration Network has been bringing researchers and makers of health apps and devices together to explore the connections between community environments, individual behaviors and health. One such study enables RunKeeper participants to share their data with researchers who want to understand how the built environment relates to types and amounts of exercise over time.

Researchers at the University of Pennsylvania—another RWJF grantee—are exploring whether what people post online could give health care providers clues about their patient’s health. 3,000 people have agreed to give these researchers access to their electronic health records along with their Facebook, Instagram and Twitter data.

Using Apple’s ResearchKit platform, grantee Sage Bionetworks has been able to capture data on abilities affected by Parkinson’s Disease. Thousands of people completed tasks using their iPhones—from completing a speed tapping exercise on their phone’s touchscreen to measure dexterity, to using their phone’s microphone to record themselves saying “Aaaaah” to measure vocal characteristics—to generate that data. What’s more, over 10,000 of these individuals have agreed to share their data with researchers worldwide to help accelerate our understanding of Parkinson’s. Encouraged by this incredible response, we recently launched the Mood Challenge, seeking proposals from researchers who want to use ResearchKit to further the understanding of mood and how it relates to daily life. And soon, Android users will also be able to participate in mobile health studies thanks to ResearchStack.

The question of privacy has been central to all of these data sharing efforts—and it’s a big one. To get people to share their data, they need to feel comfortable doing so. What we’ve learned is that we can gain that comfort and trust by designing studies in ways that allow people to choose how to share their data and with whom. We have been excited to see that so many people are willing to donate their data for the public good. And we are hopeful that this number will grow. To us, that demonstrates a real shared value around health.   

Now, with all this personal health data at our fingertips, we have a responsibility to make that data actionable—to share back meaningful information with citizens, providers, and policy makers so they can make choices that support the health of their families, their communities, and themselves. While progress has been made, there are still hurdles to overcome and still so much work to do to maximize the impact of this shared data.

For data to be actionable, it needs to be relevant and representative of healthy people and those who are ill, and needs to represent all facets of the American population, not just those who regularly visit their provider or purchased a smart watch. It also needs to be inclusive of data about the social determinants of health. We are concerned that research and applications built using data that is only representative of a certain subset of the population will produce solutions that only help those communities.

Actionable data doesn’t always need to be quantitative. We also need to understand how emotions and qualitative information can be incorporated into data-driven efforts to improve health and well-being. We note with interest the work of MyCounterpane, who is working with individuals and caregivers living with Multiple Sclerosis to collect emotions as a way to understand the impact of the disease beyond the physical effects. Grantee Atlas of Caregiving is using wearable cameras and sensors to understand how caregivers spend their time, how stress plays into caregiving, and which activities are most stressful. Importantly, they also measure moments of joy and happiness.

How can you help? If you have a cutting-edge idea for how to improve learning from health data, consider joining the Health Data Exploration network or submitting a proposal to the Foundation. Finally, find me on Twitter and keep the conversation going. I’d love to hear from you.

Precision medicine for understudied populations

by Roxana Daneshjou, guest contributor

Precision medicine, which leverages a patient’s genetics to help make medical decisions, has the potential to revolutionize medicine. Its applications are numerous: from predicting who may have an adverse reaction to a medication, to allowing targeted therapies of cancer with particular mutations. In 2015, President Obama’s State of the Union announced an initiative to further our understanding of precision medicine and to build the infrastructure to implement it. An important part of this initiative is building a large diverse research cohort to help discover disease-gene and drug-gene associations. The key word is diverse – because genetic risk factors can be population-specific. In the past, individuals of African, Hispanic, and Middle Eastern ancestry have been understudied. Only by including individuals from all different ancestral backgrounds can we hope to implement precision medicine in an inclusive way.

In 2011, Russ Altman’s research group was pondering the importance of inclusive precision medicine when it became clear that several studies examining the baseline genetic variation across the globe, 1000 Genomes and the International HapMap Project, had an underrepresentation of Middle Eastern populations. As a scientist of Iranian descent who had undergone direct-to-consumer genotyping with 23andMe, I wondered how to make sense of my data when no baseline genetic study of the Iranian population existed. When scientists Dr. Mostafa Ronaghi and Dr. Pardis Sabeti approached Dr. Altman’s group about the idea of creating such a baseline, I was immediately interested. Through the generous support of the PARSA Foundation, we began our journey to create a genetic baseline of the Iranian population.

Our first roadblock appeared when we spent months exploring the feasibility of collecting samples in Iran. Due to the economic sanctions at that time, it turned out that establishing a collaboration with an Iranian university and collecting samples there would be nearly impossible. In the United States, however, the Iranian diaspora has created a sizeable population generally representing the diversity of sub-ethnic groups in Iran.  We turned to this population to collect our samples and conducted high coverage sequencing of 77 healthy individuals. This data can be used for answering some questions about the population’s history and also as a baseline for scientists interested in studying disease in this population.

Since our aim is to enable other scientists to answer important questions about disease risk and treatment in individuals of Iranian ancestry, we are committed to sharing our data. Our website, irangenes.com, already has summary data of population level genetic variants. We’re currently working on uploading all of our genomic data on a secure server so that scientists can submit proposals to use our raw data.  Since the sanctions on Iran were lifted in January 2016, we have corresponded with scientists in Iran who are using our summary data to help advance precision medicine there. We are also working on uploading all of our genomic data to a secure server as a part of the precision medicine initiative so that scientists can submit proposals to use our raw data.

In addition to the medical applications, we were also interested in learning more about the Iranian population’s history through its genetics. Based on our data, the Iranian population is genetically distinct from other Middle Eastern populations. However, it is important to remember that any two humans share 99.9% of their genome. Moreover, as has been seen in previous studies in other populations, the different Iranian sub-ethnic groups have a lot of genetic overlap. Though capturing the breadth of human genetic diversity is important to inclusive precision medicine, these studies also show us that – at our core – we are a singular human family.

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Roxana Daneshjou is an MD/Ph.D. student at Stanford and is supported by the Paul and Daisy Soros Fellowship for New Americans.

Online live event on genomics and medicine: Where promise meets clinical practice

It was big news this week: A major change shift in cardiac care recommendations.

The American Heart Association and the American College of Cardiology released new guidelines that adjusted expectations for lowering low-density lipoprotein (LDL) levels to a specific number, and adding other risk factors into the equation of who should take statins, a class of drugs designed to treat high cholesterol.

shutterstock_118323973Experts developed the guidelines based on population studies that averaged the benefits of cholesterol-lowering drugs across millions of people. But for some people, the medications do not work as well and in some cases, cause adverse affects, such as painful leg cramping.  What would it take to customize cholesterol lowering with the best drug at the right dose?

Enter the emerging field of personalized medicine, or National Human Genome Research Institute (NHGRI) calls it, genomic medicine. Doctors have known for decades that some people are at higher risk of a common disorder such as diabetes, or react poorly to medications. Since the completion of the Human Genome Project in 2003, NHGRI has led numerous studies to understand the genetic differences in people at increased risk for disease and to understand how best to use genetic testing to customize an individual’s medical treatment.

The field of cancer care is likely one of the first beneficiaries. Cancer is a genetic disease.  Genomic research is increasingly helping to inform and shape diagnosis and treatment recommendations.

One example: Earlier this month, researchers at the University of Michigan identified a type of mutation that develops after breast cancer patients take anti-estrogen therapies. The mutation may cause some patients to become resistant to this therapy, but blood test monitoring may mean clinicians can spot the advancing mutation and tinker with treatment before resistance becomes full-blown.

Glioblastoma multiforme (GBM) is a common and deadly type of brain cancer that will kill some 14,000 people this year. Most patients die within 14 months of their diagnosis. In 2008, GBM became the first cancer that researchers from The Cancer Genome Atlas Research Network began to systemically study.

Researchers discovered GBM fell into four different molecular subtypes, discovering in the process that chemotherapy and radiation did not work as well for some of the genotypes. Patients with that molecular profile, then, may be able to avoid toxic treatment and its ravaging side effects. The work also uncovered new details on mutations in genes that promote cancer, called oncogenes, and others that protect against cancer, known as tumor suppressor genes.

“The Cancer Genome Atlas project, a collaboration between the National Cancer Institute and NHGRI as been analyzing 500 cancer samples of one common cancer and comparing them to 500 normal genomes from the same patient to see what has changed and causes them to grow out of control,” says Larry J. Thompson, NHGRI spokesperson. “TCGA has studied more than a dozen common cancers and work continues at a rapid pace to understand genetic changes that cause most tumors.

“Genomics is also changing the way some cancers are categorized. For example, we know now that on a cellular level a lung cancer can be closely related to a form of colon cancer, which may speed repurposing of some cancer drugs,” he says.

The race is on.  In September, The National Institutes of Health (NIH) issued three grants totaling more than $25 million for three research groups to develop a database of the millions of genomic variants potentially relevant to human disease, and to decipher which may be useful for clinical practice.

“We’re in the early stages of these applications. We’re learning so much, so fast, it’s hard to know what’s going to break first, and what will turn out to be clinically relevant and meaningful,” Thompson says.

What’s possible on the horizon?  We’ll ask that of NHGRI’s Director, Dr. Eric Green, who will be joining TEDMED and other guests this Thursday for a live Google+ Hangout event at 2pm ET.  Among the topics we’ll discuss:

  • What is technically possible now, and what is the medical rationale for wanting to push this area of scientific research?
  • What are the barriers to progress?
  • Where will the field be in five years?
  • How is genomic research changing clinical practices?
  • How will we address regulations, reimbursement issues and other practical considerations?

Click here to register.  We’ll take questions from our Twitter, Google+ and Facebook audiences and will answer as many as possible.

Want to help heal the world? Start by sharing your health data

What can you do help yourself, family, friends — and why not everyone? — to heal from and perhaps avoid deadly diseases? Why not share your personal health data to help a new multi-industry, collaborative effort to improve therapies?

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That’s the drive behind a new website, MeForYou.org, part of a University of California at San Francisco (UCSF) awareness campaign around precision medicine, the topic of the OME Summit last week.

UCSF Chancellor and TEDMED 2013 speaker Susan Desmond-Hellmann is a leader in advancing precision medicine, which calls for disease treatment that integrates genomic knowledge and other molecular research with input from patients’ health records, along with social and environmental data.

Ideally, precision medicine will lead to improved diagnosing and customized treatment based on personal genetics, and include a feedback loop to monitor effectiveness. UCSF already has a number of related initiatives on board, including:

  • study on fronto-temporal dementia – more common in people under age 60 than Alzheimer’s disease – that is integrating all known data on the disease, with the goal of homing in on the genetic and molecular causes;
  • A large-scale breast cancer project that tracks patients’ progress during a clinical trial, charts it against population-based data and adapts therapy accordingly;
  • A collaboration with Kaiser Permanente that has resulted in the world’s largest and most diverse genetic database, tied to environmental exposures, telomere lengths and in some cases decades of electronic health records.

David Arrington, UCSF spokesperson, says MeForYou aims to drive conversation about something we all own — individual genetic and health data — and someone we know whom might benefit from it. Now in its initial phase, the campaign simply asks users, “What can you do?” prompting them to share their photo and dedicate their efforts to the health of one or more people.

“Never before in history have we had the right convergence of infrastructure, computer power and understanding of biology,” Arrington says, “and now we need to change the social contract. We’re trying to put a new thought into the public consciousness of, medically speaking, what can they do for someone else? What can I do to take a meaningful step?  And then, If I can pledge to help this person, why not the general population?”

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UCSF is still working to gather partners in the effort, which could include advocacy groups, non-profits, biomed and health tech companies and insurers, and to work out logistics on how to scale it up, ideally to a global level. Still, most integral to its success are contributors, who will receive email updates about the initiative as it progresses about how to go about contributing data.

“This is a grassroots effort. Our hope is that people will start showing up to their checkups being well-informed, and say, “I see you’re entering something in my medical records.  Where’s that going?  How is it helping my family and my kids?” Arrington says.

Visit MeForYou.org for more information and to make a dedication.

Related: TEDMED speakers Peggy Hamburg and Francis Collins discuss precision medicine with Desmond-Hellmann.