Engaging the patient to create a culture of health citizenship

P4C

Health Citizenship panel discussion at Partnering for Cures: L to R: Lucia Savage, Roni Zeiger,  Claudia Williams, Jennifer Mills, Kathy Hudson, Beth Meagher

One of the buzz phrases in healthcare today is “patient engagement”. It seems that you can’t go to a medical or scientific conference without coming across a panel discussion on the topic. A recent Partnering For Cures* event in San Francisco was no exception. But here the conversation took on a very different tone, one that challenged what the term meant and then said that if we are really serious about engaging patients, then doctors and drug companies need to change the way they think and operate.

That tone was set from the start of the discussion when moderator Claudia Williams said even the term “patient engagement” suggests that it is something “being imposed, or at least allowed, from the outside; by experts and doctors and those in charge.”

Williams quoted Erin Moore, the mother of a young boy with cystic fibrosis saying “No one is more engaged than the patient. I want the experts, the doctors, the pharmaceutical companies to be engaged.”

Need to train doctors

Dr. Roni Zeiger, the former Chief Health Strategist at Google, said doctors aren’t trained to truly listen to and engage with patients, and that has to change:

“I sometimes think of myself as a recovering paternal physician. When I listen to and learn from patients and families I am surprised, every time, at the breadth and depth of the conversations. All of the things that we, in the medical field, do from designing a waiting room to designing a clinical trial to deciding when and how to have a conversation, we bring a tremendous amount of assumptions to those. And those assumptions are often wrong. I think that on a daily basis we should be looking at the key work we do and ask are there assumptions here I should throw away and talk to those I serve and get their help in redesigning things in a way that makes more sense.”

Jennifer Mills, the Director of Patient Engagement (that phrase again) at biotech giant Genentech, said those mistakes are made by everyone in the field:

“The biggest assumption for me is thinking about patients with a capital P, as a homogeneous group, instead of realizing they are also individuals. We need to address them as a group and as individuals depending on the circumstances.”

Caregivers count too

For example as people get older and rely on a partner or spouse to take care of them it may be important to not just engage with the patient but also with the caregiver. And the needs for each of them may not be the same.

At that point the conversation turned to the use of data. Lucia Savage, the Chief Privacy and Regulatory Officer at Omada Health, said it is going to be increasingly important to give people control over their own medical data, and sometimes the medical data of others.

“Caregivers need access to healthcare records. For example, I can check my mom’s labs. If I message her doctors they can share that information with me. It’s great because it helps us help her lead an independent life as an 80 year old.”

Savage also pointed out that we need to be careful how we interpret data. She said she could go shopping and buy three extra-large bags of potato chips. On the face of it that doesn’t look good. But did she buy those chips for herself or her daughter’s soccer team. The data is the same. The implications are very different.

Partnership not patronizing

The discussion ended with an attempt to outline what being a good health citizen means. Just as citizenship involves both rights and responsibilities on the part of the individual and society, health citizenship too involves rights and responsibilities on the part of the individual and the biomedical research and health care world. Patients deserve to be treated as individuals who have a vested interest in their own health. They don’t need “experts” to talk down or patronize them or assume they know best.

Mills says she is seeing progress in this area:

“Companies are moving from assuming what patients need to asking what they need. We once assumed that if we were in the therapeutic area long enough we didn’t need to ask what patients need. I’m seeing that change.”

Deloitte Consulting’s Beth Meagher said we need to look beyond technology and focus on the people:

“Humility is going to be the killer app. The true innovators are really being humble and realizing that to have the kind of impact they are looking for, there is a need to work in a way they haven’t before. “

*Partnering for Cures is a project of Michael Milken’s FasterCures, whose goal is to save lives by speeding up and improving the medical research system.

 

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Turning the corner with the FDA and NIH; CIRM creates new collaborations to advance stem cell research

FDAThis blog is part of the Month of CIRM series on the Stem Cellar

A lot can change in a couple of years. Just take our relationship with the US Food and Drug Administration (FDA).

When we were putting together our Strategic Plan in 2015 we did a survey of key players and stakeholders at CIRM – Board members, researchers, patient advocates etc. – and a whopping 70 percent of them listed the FDA as the biggest impediment for the development of stem cell treatments.

As one stakeholder told us at the time:

“Is perfect becoming the enemy of better? One recent treatment touted by the FDA as a regulatory success had such a high clinical development hurdle placed on it that by the time it was finally approved the standard of care had evolved. When it was finally approved, five years later, its market potential had significantly eroded and the product failed commercially.”

Changing the conversation

To overcome these hurdles we set a goal of changing the regulatory landscape, finding a way to make the system faster and more efficient, but without reducing the emphasis on the safety of patients. One of the ways we did this was by launching our “Stem Cell Champions” campaign to engage patients, patient advocates, the public and everyone else who supports stem cell research to press for change at the FDA. We also worked with other organizations to help get the 21st Century Cures Act passed.

21 century cures

Today the regulatory landscape looks quite different than it did just a few years ago. Thanks to the 21st Century Cures Act the FDA has created expedited pathways for stem cell therapies that show promise. One of those is called the Regenerative Medicine Advanced Therapy (RMAT) designation, which gives projects that show they are both safe and effective in early-stage clinical trials the possibility of an accelerated review by the FDA. Of the first projects given RMAT designation, three were CIRM-funded projects (Humacyte, jCyte and Asterias)

Partnering with the NIH

Our work has also paved the way for a closer relationship with the National Institutes of Health (NIH), which is looking at CIRM as a model for advancing the field of regenerative medicine.

In recent years we have created a number of innovations including introducing CIRM 2.0, which dramatically improved our ability to fund the most promising research, making it faster, easier and more predictable for researchers to apply. We also created the Stem Cell Center  to make it easier to move the most promising research out of the lab and into clinical trials, and to give researchers the support they need to help make those trials successful. To address the need for high-quality stem cell clinical trials we created the CIRM Alpha Stem Cell Clinic Network. This is a network of leading medical centers around the state that specialize in delivering stem cell therapies, sharing best practices and creating new ways of making it as easy as possible for patients to get the care they need.

The NIH looked at these innovations and liked them. So much so they invited CIRM to come to Washington DC and talk about them. It was a great opportunity so, of course, we said yes. We expected them to carve out a few hours for us to chat. Instead they blocked out a day and a half and brought in the heads of their different divisions to hear what we had to say.

A model for the future

We hope the meeting is, to paraphrase Humphrey Bogart at the end of Casablanca, “the start of a beautiful friendship.” We are already seeing signs that it’s not just a passing whim. In July the NIH held a workshop that focused on what will it take to make genome editing technologies, like CRISPR, a clinical reality. Francis Collins, NIH Director, invited CIRM to be part of the workshop that included thought leaders from academia, industry and patients advocates. The workshop ended with a recommendation that the NIH should consider building a center of excellence in gene editing and transplantation, based on the CIRM model (my emphasis).  This would bring together a multidisciplinary disease team including, process development, cGMP manufacturing, regulatory and clinical development for Investigational New Drug (IND) filing and conducting clinical trials, all under one roof.

dr_collins

Dr. Francis Collins, Director of the NIH

In preparation, the NIH visited the CIRM-funded Stem Cell Center at the City of Hope to explore ways to develop this collaboration. And the NIH has already begun implementing these suggestions starting with a treatment targeting sickle cell disease.

There are no guarantees in science. But we know that if you spend all your time banging your head against a door all you get is a headache. Today it feels like the FDA has opened the door and that, together with the NIH, they are more open to collaborating with organizations like CIRM. We have removed the headache, and created the possibility that by working together we truly can accelerate stem cell research and deliver the therapies that so many patients desperately need.

 

 

 

 

 

 

High school students SPARK an interest in stem cell research

SPARK students at the 2017 Annual Meeting at the City of Hope.

High school is a transformative time for any student. It marks the transition from childhood to adulthood and requires discipline, dedication and determination to excel and get into their desired college or university.

The barrier to entry for college now seems much higher than when I was eighteen, but I am not worried for the current generation of high school students. That’s because I’ve met some of the brightest young minds this past week at the 2017 CIRM SPARK meeting.

SPARK is CIRM’s high school education program, which gives underprivileged students in California the opportunity to train as stem cell scientists for the summer. Students participate in a summer research internship at one of seven programs at leading research institutes in the state. They attend scientific lectures, receive training in basic lab techniques, and do an eight-week stem cell research project under the guidance of a mentor.

At the end of the summer, SPARK students congregate at the annual SPARK poster meeting where they present the fruits of their labor. Meeting these students in person is my favorite time of the year. Their enthusiasm for science and stem cell research is contagious. And when you engage them or listen to them talk about their project, it’s hard to remember that they are still teenagers and not graduate level scientists.

What impresses me most about these students is their communication skills. Each summer, I challenge SPARK students to share their summer research experience through social media and blogging, and each time they go above and beyond with their efforts. Training these students as effective science communicators is important to me. They are the next generation of talented scientists who can help humanize research for the public. They have the power to change the perception of science as a field to be embraced and one that should receive proper funding.

It’s also inspiring to me that this young generation can effectively educate their friends, family and the public about the importance of stem cell research and how it will help save the lives of patients who currently don’t have effective treatments. If you haven’t already, I highly recommend checking out the #CIRMSPARKlab hashtag on Instagram to get a taste of what this year’s group of students accomplished during their internships.

Asking students, many of whom are learning to do research for the first time, to post on Instagram once a week and write a blog about their internship is a tall task. And I believe with any good challenge, there should be a reward. Therefore, at this year’s SPARK meeting held at the City of Hope in Duarte, California, I handed out prizes.

It was very difficult to pick winners for our presentation, social media and blogging awards because honestly, all our students were excellent this year. Even Kevin McCormack, Director of CIRM’s Communications, who helped me read the students’ blogs said,

“This was really tough. The standard of the blogs this year was higher than ever; and previous years had already set the bar really high. It was really difficult deciding which were really good and which were really, really good.”

Ok, enough with the hype, I know you want to read these award-winning blogs so I’ve shared them below. I hope that they inspire you as much as they have inspired me.


Amira Hirara

Amira Hirara (Children’s Hospital Oakland Research Institute)

It was a day like any other. I walked into the room, just two minutes past 10:30am, ready for another adventurous day in the lab. Just as I settle down, I am greeted by my mentor with the most terrifying task I have ever been asked to perform, “Will you passage the cells for me…alone?” Sweat begins to pour down my cemented face as I consider what is at stake.

The procedure was possibly thirty steps long and I have only executed it twice, with the supervision of my mentor of course. To be asked to do the task without the accompaniment of an experienced individual was unthought-of. I feel my breath begin to shorten as I mutter the word “Ok”. Yet it wasn’t just the procedure that left me shaking like a featherless bird, it was the location of my expedition as well. The dreaded tissue culture room. If even a speck of dirt enters the circulating air of the biosafety cabinet, your cells are at risk of death…death! I’ll be a cell murderer. “Alright”, she said, “I’ll just take a look at the cells then you’ll be on your way.” As we walk down the hallway, my eyes began to twitch as I try to recall the first steps of the procedure. I remember freezing our plates with Poly-ornithine and laminin, which essentially simulates the extracellular environment and allows adhesion between the cell and the plate itself. I must first add antibiotics to rid the frozen plate of potential bacteria. Then I should remove my cells from the incubator, and replace the old solution with accutase and new media, to nourish the cells, as well as unbind them from the plate before. Passaging is necessary when the cell density gets too high, as the cells must be relocated to a roomier environment to better promote survival. As we approach the tissue culture room, my jaw unclenches, as I realize the whirlwind of ideas meant I know more than I thought. My mentor retrieves our cells, views them under the microscope, and deems them ‘ready for passaging’.

“Good luck Amira” she says to me with a reassuring smile. I enter the room ready for battle. Placing first my gloves and coat, I then spray my hands and all things placed in the cabinet with 70% ethanol, to insure a sterile work environment. Back to the procedure, I’ll place the cellular solution of accutase and media into a covalent tube. After, I’ll centrifuge it for two minutes until a cellular pellet forms at the bottom, then dissolve the cells in fresh media, check its density using a cell counter, and calculate the volume of cellular solution needed to add to my once frozen plates. Wait, once I do that, I’ll be all done. I eagerly execute all the steps, ensuring both accuracy and sterility in my work. Pride swells within me as I pipette my last milliliter of solution into my plate. The next day, my mentor and I stop by to check on how our sensitive neural stem cells are doing. “Wow Amira, I am impressed, your cells seem very confluent in their new home, great job!” I smile slyly and begin to nod my head. I now walk these hallways, with a puffed chest, brightened smile, and eagerness to learn. My stem cells did not die, and having the amazing opportunity to master their treatment and procedures, is something I can never forget.

 

Gaby Escobar

Gaby Escobar (Stanford University)

Walking into the lab that would become my home for the next 8 weeks, my mind was an empty canvas.  Up to that point, my perception of the realm of scientific research was one-sided. Limited to the monotonous textbook descriptions of experiments that were commonplace in a laboratory, I wanted more. I wanted to experience the alluring call of curiosity. I wanted to experience the flash of discovery and the unnerving drive that fueled our pursuit of the unknown. I was an empty canvas looking for its first artistic stroke.

Being part of the CIRM Research program, I was lucky enough to have been granted such opportunity. Through the patient guidance of my mentor, I was immersed into the limitless world of stem cell biology. From disease modeling to 3D bioprinting, I was in awe of the capabilities of the minds around me. The energy, the atmosphere, the drive all buzzed with an inimitable quest for understanding. It was all I had imagined and so, so much more.

However, what many people don’t realize is research is an arduous, painstaking process. Sample after sample day after day, frustration and doubt loomed above our heads as we tried to piece together a seemingly pieceless puzzle.  Inevitably, I faced the truth that science is not the picture-perfect realm I had imagined it to be. Rather, it is tiring, it is relentless, and it is unforgiving. But at the same time, it is incomparably gratifying. You see, the innumerable samples, the countless gels and PCRS, all those futile attempts to fruitlessly make sense of the insensible, have meaning. As we traversed through the rollercoaster ride of our project, my mentor shared a personal outlook that struck very deeply with me: her motivation to work against obstacle after obstacle comes not from the recognition or prestige of discovering the next big cure but rather from the notion that one day, her perseverance may transform someone’s life for the good.  And in that, I see the beauty of research and science: the coming together of minds and ideas and bewildering intuitions all for the greater good.

As I look back, words cannot express the gratitude I feel for the lessons I have learned. Undoubtedly, I have made countless mistakes (please don’t ask how many gels I’ve contaminated or pipettes I have dropped) but I’ve also created the most unforgettable of memories. Memories that I know I will cherish for the journey ahead of me. Having experienced the atmosphere of a vibrant scientific community, I have found a second home, a place that I can explore and question and thrive. And although not every day will hold the cure to end all diseases or hand an answer on a silver platter, every day is another opportunity.  And with that, I walk away perhaps not with the masterpiece of art that I had envisioned in my mind but rather with a burning spark of passion, ready to ignite.

 

Anh Vo

Ahn Vo (UC Davis)

With college selectivity increasing and acceptance rates plummeting, the competitive nature within every student is pushed to the limit. In high school, students are expected to pad up their resumes and most importantly, choose an academic path sooner rather than later. However, at 15, I felt too young to experience true passion for a field. As I tried to envision myself in the future, I wondered, would I be someone with the adrenaline and spirit of someone who wants to change the world or one with hollow ambitions, merely clinging onto a paycheck with each day passing? At the very least, I knew that I didn’t want to be the latter.

The unrelenting anxiety induced by the uncertainty of my own ambitions was intoxicating. As my high school career reached its halfway mark, I felt the caving pressure of having to choose an academic path.

“What do you want to be?” was one of the first questions that my mentor, Whitney Cary, asked me. When I didn’t have an answer, she assured me that I needed to keep my doors open, and the SPARK program was the necessary first step that I needed to take to discovering my passion.

As I reflected on my experience, the SPARK program was undoubtedly the “first step”. It was the first step into a lab and above all, into a community of scientists, who share a passion for research and a vehement resolve to contribute to scientific merit. It was the integration into a cohort of other high school students, whose brilliance and kindness allowed us to forge deeper bonds with each other that we will hold onto, even as we part ways. It was the first nervous step into the bay where I met the Stem Cell Core, a team, whose warm laughter and vibrancy felt contagious. Finally, it was the first uncertain stumble into the tissue culture room, where I conceived a curiosity for cell culture that made me never stop asking, “Why?”

With boundless patience, my mentor and the Stem Cell Core strove to teach me techniques, such as immunocytochemistry and continually took the time out of their busy day to reiterate concepts. Despite my initial blunders in the hood, I found myself in a place without judgement, and even after discouraging incidents, I felt a sense of consolation in the witty and good-humored banter among the Stem Cell Core. At the end of every day, the unerring encouragement from my mentor strengthened my resolve to continue improving and incited an earnest excitement in me for the new day ahead. From trembling hands, nearly tipping over culture plates and slippery gloves, overdoused in ethanol, I eventually became acquainted with daily cell culture, and most importantly, I gained confidence and pride in my work.

I am grateful to CIRM for granting me this experience that has ultimately cultivated my enthusiasm for science and for the opportunity to work alongside remarkable people, who have given me new perspectives and insights. I am especially thankful to my mentor, whose stories of her career journey have inspired me to face the future with newfound optimism in spite of adversity.

As my internship comes to a close, I know that I have taken my “first step”, and with a revived mental acquisitiveness, I eagerly begin to take my second.

Other 2017 SPARK Awards

Student Speakers: Candler Cusato (Cedars-Sinai), Joshua Ren (Stanford)

Instagram/Social Media: Jazmin Aizpuru (UCSF), Emily Beckman (CHORI), Emma Friedenberg (Cedars-Sinai)

Poster Presentations: Alexander Escudero (Stanford), Jamie Kim (CalTech), Hector Medrano (CalTech), Zina Patel (City of Hope)


Related Links:

CIRM & NIH: a dynamic duo to advance stem cell therapies

NIH

National Institutes of Health

There’s nothing more flattering than to get an invitation, out of the blue, from someone you respect, and be told that they are interested in learning about the way you work, to see if it can help them improve the way they work.

That’s what happened to CIRM recently. I will let Randy Mills, who was our President & CEO at the time, pick up the story:

“Several weeks ago I got a call from the head of the National Heart. Lung and Blood Institute (NHLBI) asking would we be willing to come out to the National Institutes of Health (NIH) and talk about what we have been doing, the changes we have made and the impact they are having.”

Apparently people at the NIH had been reading our Strategic Plan and our Annual Report and had been hearing good things about us from many different individuals and organizations. We also heard that they had been motivated to engage more fully with the regenerative medicine community following the passage of the 21st Century Cures Act.

We were expecting a sit down chat with them but we got a lot more than that. They blocked out one and a half days for us so that we had the time to engage in some in-depth, thoughtful conversations about how to advance the field.

collins-portrait_1

Dr. Francis Collins, NIH Director

The meeting was kicked off by both Francis Collins, the NIH Director, and Gary Gibbons, the NHLBI Director. Then the CIRM team – Dr. Mills, Dr. Maria Millan, Gabe Thompson and James Harrison – gave a series of presentations providing an overview of how CIRM operates, including our vision and strategic priorities, our current portfolio, the lessons learned so far, our plans for the future and the challenges we face.

The audience included the various heads and representatives from the various NIH Institutes who posed a series of questions for us to answer, such as:

  • What criteria do we use to determine if a project is ready for a clinical trial?
  • How do we measure success?
  • How have our strategies and priorities changed under CIRM 2.0?
  • How well are those strategies working?

The conversation went so well that the one day of planned meetings were expanded to two. Maria Millan, now our interim President & CEO, gave an enthusiastic summary of the talks

“The meetings were extremely productive!  After meeting with Dr. Collins’ group and the broader institute, we had additional sit down meetings.   The NIH representatives reported that they received such enthusiastic responses from Institute heads that they extended the meeting into a second day. We met with with the National Institutes of Dental and Craniofacial Research, Heart, Lung and Blood, Eye Institute, Institute on Aging, Biomedical Imaging and Bioengineering, Diabetes, and Digestive and Kidney Diseases, and the National Center for Advancing Translational Sciences.  We covered strategic and operational considerations for funding the best science in the stem cell and regenerative medicine space.  We explored potential avenues to join forces and leverage the assets and programs of both organizations, to accelerate the development of regenerative medicine and stem cell treatments.”

This was just a first meeting but it laid the groundwork for what we hope will be a truly productive partnership. In fact, shortly after returning from Washington, D.C., CIRM was immediately invited to follow-up NIH workgroups and meetings.

As this budding partnership progresses we’ll let you know how it’s working out.

CIRM Alpha Clinics Network charts a new course for delivering stem cell treatments

Sometimes it feels like finding a cure is the easy part; getting it past all the hurdles it must overcome to be able to reach patients is just as big a challenge. Fortunately, a lot of rather brilliant minds are hard at work to find the most effective ways of doing just that.

Last week, at the grandly titled Second Annual Symposium of the CIRM Alpha Stem Cell Clinics Network, some of those minds gathered to talk about the issues around bringing stem cell therapies to the people who need them, the patients.

The goal of the Alpha Clinics Network is to accelerate the development and delivery of stem cell treatments to patients. In doing that one of the big issues that has to be addressed is cost; how much do you charge for a treatment that can change someone’s life, even save their life? For example, medications that can cure Hepatitis C cost more than $80,000. So how much would a treatment cost that can cure a disease like Severe Combined Immunodeficiency (SCID)? CIRM-funded researchers have come up with a cure for SCID, but this is a rare disease that affects between 40 – 100 newborns every year, so the huge cost of developing this would fall on a small number of patients.

The same approach that is curing SCID could also lead to a cure for sickle cell disease, something that affects around 100,000 people in the US, most of them African Americans. Because we are adding more people to the pool that can be treated by a therapy does that mean the cost of the treatment should go down, or will it stay the same to increase profits?

Jennifer Malin, United Healthcare

Jennifer Malin from United Healthcare did a terrific job of walking us through the questions that have to be answered when trying to decide how much to charge for a drug. She also explored the thorny issue of who should pay; patients, insurance companies, the state? As she pointed out, it’s no use having a cure if it’s priced so high that no one can afford it.

Joseph Alvarnas, the Director of Value-based Analytics at City of Hope – where the conference was held – said that in every decision we make about stem cell therapies we “must be mindful of economic reality and inequality” to ensure that these treatments are available to all, and not just the rich.

“Remember, the decisions we make now will influence not just the lives of those with us today but also the lives of all those to come.”

Of course long before you even have to face the question of who will pay for it, you must have a treatment to pay for. Getting a therapy through the regulatory process is challenging at the best of times. Add to that the fact that many researchers have little experience navigating those tricky waters and you can understand why it takes more than eight years on average for a cell therapy to go from a good idea to a clinical trial (in contrast it takes just 3.2 years for a more traditional medication to get into a clinical trial).

Sunil Kadim, QuintilesIMS

Sunil Kadam from QuintilesIMS talked about the skills and expertise needed to navigate the regulatory pathway. QuintilesIMS partners with CIRM to run the Stem Cell Center, which helps researchers apply for and then run a clinical trial, providing the guidance that is essential to keeping even the most promising research on track.

But, as always, at the heart of every conference, are the patients and patient advocates. They provided the inspiration and a powerful reminder of why we all do what we do; to help find treatments and cures for patients in need.

The Alpha Clinic Network is only a few years old but is already running 35 different clinical trials involving hundreds of patients. The goal of the conference was to discuss lessons learned and share best practices so that number of trials and patients can continue to increase.

The CIRM Board is also doing its part to pick up the pace, approving funding for up to two more Alpha Clinic sites.  The deadline to apply to be one of our new Alpha Clinics sites is May 15th, and you can learn more about how to apply on our funding page.

Since joining CIRM I have been to many conferences but this was, in my opinion, the best one I have ever intended. It brought together people from every part of the field to give the most complete vision for where we are, and where we are headed. The talks were engaging, and inspiring.

Kristin Macdonald was left legally blind by retinitis pigmentosa, a rare vision-destroying disease. A few years ago she became the first person to be treated with a CIRM-funded therapy aimed to restoring some vision. She says it is helping, that for years she lived in a world of darkness and, while she still can’t see clearly, now she can see light. She says coming out of the darkness and into the light has changed her world.

Kristin Macdonald

In the years to come the Alpha Clinics Network hopes to be able to do the same, and much more, for many more people in need.

To read more about the Alpha Clinics Meeting, check out our Twitter Moments.

Curing the Incurable through Definitive Medicine

“Curing the Incurable”. That was the theme for the first annual Center for Definitive and Curative Medicine (CDCM) Symposium held last week at Stanford University, in Palo Alto, California.

The CDCM is a joint initiative amongst Stanford Healthcare, Stanford Children’s Health and the Stanford School of Medicine. Its mission is to foster an environment that accelerates the development and translation of cell and gene therapies into clinical trials.

The research symposium focused on “the exciting first-in-human cell and gene therapies currently under development at Stanford in bone marrow, skin, cardiac, neural, pancreatic and neoplastic diseases.” These talks were organized into four different sessions: cell therapies for neurological disorders, stem cell-derived tissue replacement therapies, genome-edited cell therapies and anti-cancer cell-based therapies.

A few of the symposium speakers are CIRM-funded grantees, and we’ll briefly touch on their talks below.

Targeting cancer

The keynote speaker was Irv Weissman, who talked about hematopoietic or blood-forming stem cells and their value as a cell therapy for patients with blood disorders and cancer. One of the projects he discussed is a molecule called CD47 that is found on the surface of cancer cells. He explained that CD47 appears on all types of cancer cells more abundantly than on normal cells and is a promising therapeutic target for cancer.

Irv Weissman

Irv Weissman

“CD47 is the first gene whose overexpression is common to all cancer. We know it’s molecular mechanism from which we can develop targeted therapies. This would be impossible without collaborations between clinicians and scientists.”

 

At the end of his talk, Weissman acknowledged the importance of CIRM’s funding for advancing an antibody therapeutic targeting CD47 into a clinical trial for solid cancer tumors. He said CIRM’s existence is essential because it “funds [stem cell-based] research through the [financial] valley of death.” He further explained that CIRM is the only funding entity that takes basic stem cell research all the way through the clinical pipeline into a therapy.

Improving bone marrow transplants

judith shizuru

Judith Shizuru

Next, we heard a talk from Judith Shizuru on ways to improve current bone-marrow transplantation techniques. She explained how this form of stem cell transplant is “the most powerful form of cell therapy out there, for cancers or deficiencies in blood formation.” Inducing immune system tolerance, improving organ transplant outcomes in patients, and treating autoimmune diseases are all applications of bone marrow transplants. But this technique also carries with it toxic and potentially deadly side effects, including weakening of the immune system and graft vs host disease.

Shizuru talked about her team’s goal of improving the engraftment, or survival and integration, of bone marrow stem cells after transplantation. They are using an antibody against a molecule called CD117 which sits on the surface of blood stem cells and acts as an elimination signal. By blocking CD117 with an antibody, they improved the engraftment of bone marrow stem cells in mice and also removed the need for chemotherapy treatment, which is used to kill off bone marrow stem cells in the host. Shizuru is now testing her antibody therapy in a CIRM-funded clinical trial in humans and mentioned that this therapy has the potential to treat a wide variety of diseases such as sickle cell anemia, leukemias, and multiple sclerosis.

Tackling stroke and heart disease

img_1327We also heard from two CIRM-funded professors working on cell-based therapies for stroke and heart disease. Gary Steinberg’s team is using human neural progenitor cells, which develop into cells of the brain and spinal cord, to treat patients who’ve suffered from stroke. A stroke cuts off the blood supply to the brain, causing the death of brain cells and consequently the loss of function of different parts of the body.  He showed emotional videos of stroke patients whose function and speech dramatically improved following the stem cell transplant. One of these patients was Sonia Olea, a young woman in her 30’s who lost the ability to use most of her right side following her stroke. You can read about her inspiring recover post stem cell transplant in our Stories of Hope.

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

Joe Wu followed with a talk on adult stem cell therapies for heart disease. His work, which is funded by a CIRM disease team grant, involves making heart cells called cardiomyocytes from human embryonic stem cells and transplanting these cells into patient with end stage heart failure to improve heart function. His team’s work has advanced to the point where Wu said they are planning to file for an investigational new drug (IND) application with the US Food and Drug Administration (FDA) in six months. This is the crucial next step before a treatment can be tested in clinical trials. Joe ended his talk by making an important statement about expectations on how long it will take before stem cell treatments are available to patients.

He said, “Time changes everything. It [stem cell research] takes time. There is a lot of promise for the future of stem cell therapy.”

Avalanches of exciting new stem cell research at the Keystone Symposia near Lake Tahoe

From January 8th to 13th, nearly 300 scientists and trainees from around the world ascended the mountains near Lake Tahoe to attend the joint Keystone Symposia on Neurogenesis and Stem Cells at the Resort at Squaw Creek. With record-high snowfall in the area (almost five feet!), attendees had to stay inside to stay warm and dry, and even when we lost power on the third day on the mountain there was no shortage of great science to keep us entertained.

Boy did it snow at the Keystone Conference in Tahoe!

Boy did it snow at the Keystone Conference in Tahoe!

One of the great sessions at the meeting was a workshop chaired by CIRM’s Senior Science Officer, Dr. Kent Fitzgerald, called, “Bridging and Understanding of Basic Science to Enable/Predict Clinical Outcome.” This workshop featured updates from the scientists in charge of three labs currently conducting clinical trials funded and supported by CIRM.

Regenerating injured connections in the spinal cord with neural stem cells

Mark Tuszynski, UCSD

Mark Tuszynski, UCSD

The first was a stunning talk by Dr. Mark from UCSD who is investigating how neural stem cells can help outcomes for those with spinal cord injury. The spinal cord contains nerves that connect your brain to the rest of your body so you can sense and move around in your environment, but in cases of severe injury, these connections are cut and the signal is lost. The most severe of these injuries is a complete transection, which is when all connections have been cut at a given spot, meaning no signal can pass through, just like how no cars could get through if a section of the Golden Gate Bridge was missing. His lab works in animal models of complete spinal cord transections since it is the most challenging to repair.

As Dr. Tuszynski put it, “the adult central nervous system does not spontaneously regenerate [after injury], which is surprising given that it does have its own set of stem cells present throughout.” Their approach to tackle this problem is to put in new stem cells with special growth factors and supportive components to let this process occur.

Just as most patients wouldn’t be able to come in for treatment right away after injury, they don’t start their tests until two weeks after the injury. After that, they inject neural stem cells from either the mouse, rat, or human spinal cord at the injury site and then wait a bit to see if any new connections form. Their group has shown very dramatic increases in both the number of new connections that regenerate from the injury site and extend much further than previous efforts have shown. These connections conduct electrochemical messages as normal neurons do, and over a year later they see no functional decline or tumors forming, which is often a concern when transplanting stem cells that normally like to divide a lot.

While very exciting, he cautions, “this research shows a major opportunity in neural repair that deserves proper study and the best clinical chance to succeed”. He says it requires thorough testing in multiple animal models before going into humans to avoid a case where “a clinical trial fails, not because the biology is wrong, but because the methods need tweaking.”

Everyone needs support – even dying cells

The second great talk was by Dr. Clive Svendsen of Cedars-Sinai Regenerative Medicine Institute on how stem cells might help provide healthy support cells to rescue dying neurons in the brains of patients with neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s. Some ALS cases are hereditary and would be candidates for a treatment using gene editing techniques. However, around 90 percent of ALS cases are “sporadic” meaning there is no known genetic cause. Dr. Svendsen explained how in these cases, a stem cell-based approach to at least fix the cellular cause of the disease, would be the best option.

While neurons often capture all the attention in the brain, since they are the cells that actually send messages that underlie our thoughts and behaviors, the Svendsen lab spends a great deal of time thinking about another type of cell that they think will be a powerhouse in the clinic: astrocytes. Astrocytes are often labeled as the support cells of the brain as they are crucial for maintaining a balance of chemicals to keep neurons healthy and functioning. So Dr. Svendsen reasoned that perhaps astrocytes might unlock a new route to treating neurodegenerative diseases where neurons are unhealthy and losing function.

ALS is a devastating disease that starts with early muscle twitches and leads to complete paralysis and death usually within four years, due to the rapid degeneration of motor neurons that are important for movement all over the body. Svendsen’s team found that by getting astrocytes to secrete a special growth factor, called “GDNF”, they could improve the survival of the neurons that normally die in their model of ALS by five to six times.

After testing this out in several animal models, the first FDA-approved trial to test whether astrocytes from fetal tissue can slow spinal motor neuron loss will begin next month! They will be injecting the precursor cells that can make these GDNF-releasing astrocytes into one leg of ALS patients. That way they can compare leg function and track whether the cells and GDNF are enough to slow the disease progression.

Dr. Svendsen shared with us how long it takes to create and test a treatment that is committed to safety and success for its patients. He says,

Clive Svendsen has been on a 15-year quest to develop an ALS therapy

Clive Svendsen 

“We filed in March 2016, submitted the improvements Oct 2016, and we’re starting our first patient in Feb 2017. [One document is over] 4500 pages… to go to the clinic is a lot of work. Without CIRM’s funding and support we wouldn’t have been able to do this. This isn’t easy. But it is doable!”

 

Improving outcomes in long-term stroke patients in unknown ways

Gary Steinberg

Gary Steinberg

The last speaker for the workshop, Dr. Gary Steinberg, a neurosurgeon at Stanford who is looking to change the lives of patients with severe limitations after having a stroke. The deficits seen after a stroke are thought to be caused by the death of neurons around the area where the stroke occurred, such that whatever functions they were involved with is now impaired. Outcomes can vary for stroke patients depending on how long it takes for them to get to the emergency department, and some people think that there might be a sweet spot for when to start rehabilitative treatments — too late and you might never see dramatic recovery.

But Dr. Steinberg has some evidence that might make those people change their mind. He thinks, “these circuits are not irreversibly damaged. We thought they were but they aren’t… we just need to continue figuring out how to resurrect them.”

He showed stunning videos from his Phase 1/2a clinical trial of several patients who had suffered from a stroke years before walking into his clinic. He tested patients before treatment and showed us videos of their difficulty to perform very basic movements like touching their nose or raising their legs. After carefully injecting into the brain some stem cells taken from donors and then modified to boost their ability to repair damage, he saw a dramatic recovery in some patients as quickly as one day later. A patient who couldn’t lift her leg was holding it up for five whole seconds. She could also touch her arm to her nose, whereas before all she could do was wiggle her thumb. One year later she is even walking, albeit slowly.

He shared another case of a 39 year-old patient who suffered a stroke didn’t want to get married because she felt she’d be embarrassed walking down the aisle, not to mention she couldn’t move her arm. After Dr. Steinberg’s trial, she was able to raise her arm above her head and walk more smoothly, and now, four years later, she is married and recently gave birth to a boy.

But while these studies are incredibly promising, especially for any stroke victims, Dr. Steinberg himself still is not sure exactly how this stem cell treatment works, and the dramatic improvements are not always consistent. He will be continuing his clinical trial to try to better understand what is going on in the injured and recovering brain so he can deliver better care to more patients in the future.

The road to safe and effective therapies using stem cells is long but promising

These were just three of many excellent presentations at the conference, and while these talks involved moving science into human patients for clinical trials, the work described truly stands on the shoulders of all the other research shared at conferences, both present and past. In fact, the reason why scientists gather at conferences is to give one another feedback and to learn from each other to better their own work.

Some of the other exciting talks that are surely laying down the framework for future clinical trials involved research on modeling mini-brains in a dish (so-called cerebral organoids). Researchers like Jürgen Knoblich at the Institute of Molecular Biotechnology in Austria talked about the new ways we can engineer these mini-brains to be more consistent and representative of the real brain. We also heard from really fundamental biology studies trying to understand how one type of cell becomes one vs. another type using the model organism C. elegans (a microscopic, transparent worm) by Dr. Oliver Hobert of Columbia University. Dr. Austin Smith, from the University of Cambridge in the UK, shared the latest about the biology of pluripotent cells that can make any cell type, and Stanford’s Dr. Marius Wernig, one of the meeting’s organizers, told us more of what he’s learned about the road to reprogramming an ordinary skin cell directly into a neuron.

Stay up to date with the latest research on stem cells by continuing to follow this blog and if you’re reading this because you’re considering a stem cell treatment, make sure you find out what’s possible and learn about what to ask by checking out closerlookatstemcells.org.


Samantha Yammine

Samantha Yammine

Samantha Yammine is a science communicator and a PhD candidate in Dr. Derek van der Kooy’s lab at the University of Toronto. You can learn more about Sam and her research on her website.

Stem cell and gene therapy research gets a good report card from industry leader

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Panel discussion at ARM State of the industry briefing: left to Right Robert Preti, Chair ARM; Jeff Walsh, bluebird bio; Manfred Rudiger, Kiadis Pharma; Barbara Sasu, Pfizer;  Thomas Farrell, Bellicum Pharmaceuticals. Photo courtesy ARM.

The state of the regenerative medicine field is strong and getting stronger. That was the bottom line verdict at the 2017 Cell and Gene Therapies State of the Industry briefing in San Francisco.

The briefing, an annual update on the field presented by the Alliance for Regenerative Medicine (ARM), gave a “by the numbers” look at the field and apart from one negative spot everything is moving in the right direction.

Robert Preti, Chair of ARM’s Board, said worldwide there are more than 750 regenerative companies working in the stem cell and gene therapy space. And those companies are increasingly moving the research out of the lab and into clinical trials in people.

For example, at the end of 2016 there were 802 clinical trials underway. That is a 21 percent growth over 2015. Those breakdown as follows:

Phase 1 – 271 (compared to 192 in 2015)

Phase 2 – 465 (compared to 376 in 2015)

Phase 3 – 66 (compared to 63 in 2015)

The bulk of these clinical trials, 45 percent, are focused on cancer. The second largest target, 11 percent, is on heart disease. The number of trials for neurological disorders and rare diseases are also growing in number.

Preti says the industry is at an important inflection point right now and that this growth is presenting new problems:

“The pipeline of products is robust and the technologies supporting that pipeline is even more robust. The technologies that are fueling the growth in clinical activity have accelerated so fast that we on the manufacturing side are playing catchup. We are at a point where we have to get serious about large scale commercial production.”

Preti also talked about “harmonization” of the regulatory process and the need to have a system that makes it easier for products approved for clinical trials in one country, to get approval for clinical trials in other countries.

Michael Werner, the executive director of ARM, said the organization has played a key role in helping promote the field and cited the recently passed 21st Century Cures Act as “a major win and a powerful statement of ARM’s leadership in this sector.”

But there was one area where the news wasn’t all positive, the ability of companies to raise capital. In 2015 companies raised $11 billion for research. In 2016 it was less than half of that, $5.3 billion.

With that somber note in mind it was appropriate that the panel discussion that followed the briefing was focused on the near-term and long-term challenges facing the field if it was to be commercially successful.

One of the big challenges was the issue of regulatory approval, and here the panel seemed to be more optimistic than in previous years.

Manfred Rüdiger of Kiadis Pharma said he was pleasantly surprised at how easy it was to work with different regulatory agencies in the US, Canada and Europe.

“We used them as a kind of free consultancy service, listening to their advice and making the changes they suggested so that we were able to use the same manufacturing process in Europe and Canada and the US.”

Jeff Walsh of bluebird bio, said the key to having a good working relationship with regulatory agencies like the Food and Drug Administration (FDA) is simple:

“Trust and transparency between you and the regulatory agencies is essential, it’s a critical factor in advancing your work. The agencies respond well when you have that trust. One thing we can’t be is afraid to ask. The agencies will tell you where their line is, but don’t be afraid to ask or to push the boundaries. This is new for everyone, companies and regulators, so if you are pushing it helps create the environment that allows you to work together to develop safe therapies that benefit patients.”

Another big issue was scalability in manufacturing; that it’s one thing to produce enough of a product to carry out a clinical trial but completely different if you are hoping to use that same product to treat millions of people spread out all over the US or the world.

And of course cost is always something that is front and center in people’s minds. How do you develop therapies that are not just safe and effective, but also affordable? How do companies ensure they will get reimbursed by health insurers for the treatments? No one had any simple answer to what are clearly very complex problems. But all recognized the need to start thinking about these now, long before the treatments themselves are even ready.

Walsh ended by saying:

“This is not just about what can you charge but what should you charge. We have a responsibility to engage with the agencies and ultimately the payers that make these decisions, in the same way we engage with regulatory agencies; with a sense of openness, trust and transparency. Too often companies wait too long, too late before turning to the payers and trying to decide what is appropriate to charge.”

 

 

Your Guide to Awesome Stem Cell Conferences in 2017

Welcome to 2017, a year that will likely be full of change and new surprises. I’m hoping that some of these surprises will be in regenerative medicine with new stem cell therapies showing promise or effectiveness in clinical trials.

A great way to stay on top of new advances in stem cell research is to attend scientific conferences and meetings. Some of them are well known and highly attended like the International Society for Stem Cell Research (ISSCR) conference, which this year will be in Boston in June. There are also a few smaller, more intimate conferences focusing on specific topics from discovery research to clinical therapies.

There are loads of stem cell meetings this year, but a few that I would like to highlight. Here’s my abbreviated stem cell research conference and meeting guide for 2017. Some are heavy duty research-focused events and probably not suitable for someone without a science background; they’re also expensive to sign up for. I’ve marked those with an * asterix.


January 8-12th, Keystone Symposium (Fee to register)*

Keystone will be hosting two concurrent stem cell meetings in Tahoe next week, which are geared for researchers in the field. One will be on neurogenesis during development and in the adult brain and the other will be on transcriptional and epigenetic control in stem cells. CIRM is one of the co-funders of this meeting and will be hosting a panel focused on translating basic research into clinical trials. Keystone symposiums are small, intimate meetings rich with scientific content and great for networking. Be on the look out for blog coverage about this meeting in the coming weeks.


February 3rd, Stanford Center for Definitive and Curative Medicine Symposium (Free to the public)

This free symposium at Stanford University in Palo Alto, CA will present first-in-human cell and gene therapies for a number of disorders including bone marrow, skin, cardiac, neural, uterine, pancreatic and neoplastic disorders. Speakers include scientists, translational biologists and clinicians. Irv Weissman, a Stanford professor and CIRM grantee focused on translational cancer research, will be the keynote speaker. Space is limited so sign up ASAP!


March 23rd, CIRM Alpha Stem Cell Clinics Symposium (Free to the public)

This free one-day meeting will bring together scientists, clinicians, patient advocates, and other partners to describe how the CIRM Alpha Stem Cell Clinics Network is making stem cell therapies a reality for patients. The City of Hope Alpha Clinic is part of a statewide effort funded by CIRM to develop a network of “Alpha Clinics” that has one unifying goal: to accelerate the development and delivery of stem cell treatments to patients.

City of Hope Medical Center and Alpha Stem Cell Clinic

City of Hope Medical Center and Alpha Stem Cell Clinic


June 14-17th, International Society for Stem Cell Research (Fee to register)*

The Annual ISSCR stem cell research conference will be hosted in Boston this year. This is an international conference focusing on new developments in stem cell science and technology. CIRM was one of the funders of the conference last year when ISSCR was in San Francisco. It’s one of my favorite research events to attend full of interesting scientific presentations and great for meeting future collaborators.


For a more comprehensive 2017 stem cell conference and meeting guide, check out Paul Knoepfler’s Niche blog.

Why Goldilocks could provide the answer to changing the way FDA regulates stem cells

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Panel on FDA regulation at World Stem Cell Summit

One of the hottest topics of the past year in regenerative medicine has been the discussion about the need for regulatory reform at the Food and Drug Administration (FDA) so it’s no surprise that topic was the subject of the first main panel discussion at the 2016 World Stem Cell Summit in West Palm Beach, Florida.

The panel, titled ‘FDA Oversight in Regenerative Medicine: What are the Options to Accelerating Translation’, kicked off with Celia Witten, Deputy Director of the Center for Biologics Evaluation and Research at the FDA. She laid out all the new steps that the agency is implementing to try and be more responsive to the needs of researchers and patients.

Perils facing pioneers

Martin McGlynn, the former CEO of StemCells Inc. was up next and he wasted little time listing the companies that had once been considered pioneers in the field only to fail for a variety of reasons. He said one of the big problems is that translational efforts, moving from a good idea to a clinical trial, take too long, saying 15 – 20 years is not unusual and that Big Pharma and strategic investors won’t invest until they see strong Phase 2 study results.

“We need to do great science and design and conduct great clinical trials to advance this field but we also have to come up with a sustainable business model to make this happen.”

A good start

He called the 21st Century Cures Act, which the US Senate approved yesterday, a good start but says many of the challenges won’t be helped by some of the new provisions:

“Many sponsors and companies don’t make it out of open label early studies, so the existence of an accelerated pathway or some of the other enabling tools included in the act will come too late for these groups.”

McGlynn warned that if we don’t take further steps, we risk falling behind the rest of the world where companies are buying up struggling US ventures:

“Many non-USA companies in Japan and China and Australia are quicker to recognize the value of many of the products and approaches that struggle here in the US.”

Too much, too little, just right

Marc Scheineson was the final speaker. He heads the food and drug law practice at Washington, DC law firm Alston & Bird and is a former Associate Commissioner for Legislative Affairs at the FDA. He began his presentation with what he said are the scariest words in the English language: “I‘m a lawyer from Washington D.C. and I’m here to help you.”

Scheineson says part of the problem is that the FDA was created long before cell therapy was possible and so it is struggling to fit its more traditional drug approval framework around stem cell therapies. As a result, this has led to completely separate regulatory processes for the transplantation of human organs and blood vessels, or for the use of whole blood or blood components.

He says it’s like the fable of Goldilocks and the Three Bears. Some of the regulation is too hard- resulting in a lengthy regulatory process that takes years to complete and costs billions of dollars – and some of the regulation is too soft allowing clinics to open up around the US offering unproven therapies. He says we need a Goldilocks approach that blends the two into regulations that are just right.

Time to take a second step

Scheineson agreed with McGlynn that the 21st Century Cures Act is a good start but it’s not enough.  He says it still relies heavily on the use of traditional criteria to regulate stem cells, and also leaves much of the interpretation of the Act to the discretion of the FDA.

“It’s a first step, an experiment to see if we can break the logjam and see if we can move things to an affordable BLA (The Biologics License Application is needed to be able to market a product once it’s approved by the FDA). But make no mistake, a cell therapy revolution is underway and I believe the FDA should seize the opportunity to promote innovation and not defensively protect the “status quo”.