Hey, what’s the big idea? CIRM Board is putting up more than $16.4 million to find out

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David Higgins, CIRM Board member and Patient Advocate for Parkinson’s disease; Photo courtesy San Diego Union Tribune

When you have a life-changing, life-threatening disease, medical research never moves as quickly as you want to find a new treatment. Sometimes, as in the case of Parkinson’s disease, it doesn’t seem to move at all.

At our Board meeting last week David Higgins, our Board member and Patient Advocate for Parkinson’s disease, made that point as he championed one project that is taking a new approach to finding treatments for the condition. As he said in a news release:

“I’m a fourth generation Parkinson’s patient and I’m taking the same medicines that my grandmother took. They work but not for everyone and not for long. People with Parkinson’s need new treatment options and we need them now. That’s why this project is worth supporting. It has the potential to identify some promising candidates that might one day lead to new treatments.”

The project is from Zenobia Therapeutics. They were awarded $150,000 as part of our Discovery Inception program, which targets great new ideas that could have a big impact on the field of stem cell research but need some funding to help test those ideas and see if they work.

Zenobia’s idea is to generate induced pluripotent stem cells (iPSCs) that have been turned into dopaminergic neurons – the kind of brain cell that is dysfunctional in Parkinson’s disease. These iPSCs will then be used to screen hundreds of different compounds to see if any hold potential as a therapy for Parkinson’s disease. Being able to test compounds against real human brain cells, as opposed to animal models, could increase the odds of finding something effective.

Discovering a new way

The Zenobia project was one of 14 programs approved for the Discovery Inception award. You can see the others on our news release. They cover a broad array of ideas targeting a wide range of diseases from generating human airway stem cells for new approaches to respiratory disease treatments, to developing a novel drug that targets cancer stem cells.

Dr. Maria Millan, CIRM’s President and CEO, said the Stem Cell Agency supports this kind of work because we never know where the next great idea is going to come from:

“This research is critically important in advancing our knowledge of stem cells and are the foundation for future therapeutic candidates and treatments. Exploring and testing new ideas increases the chances of finding treatments for patients with unmet medical needs. Without CIRM’s support many of these projects might never get off the ground. That’s why our ability to fund research, particularly at the earliest stage, is so important to the field as a whole.”

The CIRM Board also agreed to invest $13.4 million in three projects at the Translation stage. These are programs that have shown promise in early stage research and need funding to do the work to advance to the next level of development.

  • $5.56 million to Anthony Oro at Stanford to test a stem cell therapy to help people with a form of Epidermolysis bullosa, a painful, blistering skin disease that leaves patients with wounds that won’t heal.
  • $5.15 million to Dan Kaufman at UC San Diego to produce natural killer (NK) cells from embryonic stem cells and see if they can help people with acute myelogenous leukemia (AML) who are not responding to treatment.
  • $2.7 million to Catriona Jamieson at UC San Diego to test a novel therapeutic approach targeting cancer stem cells in AML. These cells are believed to be the cause of the high relapse rate in AML and other cancers.

At CIRM we are trying to create a pipeline of projects, ones that hold out the promise of one day being able to help patients in need. That’s why we fund research from the earliest Discovery level, through Translation and ultimately, we hope into clinical trials.

The writer Victor Hugo once said:

“There is one thing stronger than all the armies in the world, and that is an idea whose time has come.”

We are in the business of finding those ideas whose time has come, and then doing all we can to help them get there.

 

 

 

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Stem Cell Patient Advocates, Scientists and Doctors Unite Around a Common Cause

Some phrases just bring a smile to your face: “It’s a girl/boy”, “Congratulations, you got the job”, and “Another beer sir?” (or maybe that last one is just me). One other phrase that makes me smile is “packed house”. That’s why I was smiling so much at our Patient Advocate Event at UC San Diego last week. The room was jammed with around 150 patients and patient advocates who had come to hear about the progress being made in stem cell research.

Jonathan Thomas, Chair of the CIRM governing Board, kicked off the event with a quick run-through of our research, focusing on our clinical trials. As we have now funded 29 clinical trials, it really was a quick run-through, but JT did focus on a couple of remarkable stories of cures for patients suffering from Severe Combined Immunodeficiency (SCID) and Chronic Granulomatous Disease.

His message was simple. We have come a long way, but we still have a long way to go to fulfill our mission of accelerating stem cell treatments to patients with unmet medical needs. We have a target of 40 new clinical trials by 2020 and JT stressed our determination to do everything we can to reach that goal.

David Higgins, Parkinson’s Disease Advocate and CIRM Board Member (Credit Cory Kozlovich, UCSD)

Next up was David Higgins, who has a unique perspective. David is a renowned scientist, he’s also the Patient Advocate for Parkinson’s disease on the CIRM Board, and he has Parkinson’s disease. David gave a heartfelt presentation on the changing role of the patient and their growing impact on health and science.

In the old days, David said, the patient was merely the recipient of whatever treatment a doctor determined was appropriate. Today, that relationship is much more like a partnership, with physician and patient working together to determine the best approach.

He said CIRM tries to live up to that model by engaging the voice of the patient and patient advocate at every stage of the approval process, from shaping concepts to assessing the scientific merits of a project and deciding whether to fund it, and then doing everything we can to help it succeed.

He said California can serve as the model, but that patients need to make their voices heard at the national level too, particularly in light of the proposed huge budget cuts for the National Institutes of Health.

Dr. Jennifer Braswell. (Credit Cory Kozlovich, UCSD)

U.C. San Diego’s Dr. Jennifer Braswell gave some great advice on clinical trials, focusing on learning how to tell a good trial from a questionable one, and the questions patients need to ask before agreeing to be part of one.

She said it has to:

  • Be at a highly regarded medical center
  • Be based on strong pre-clinical evidence
  • Involved well-informed and compassionate physicians and nurses
  • Acknowledge that it carries some risk.

“You all know that if it sounds too good to be true, it probably is. If someone says a clinical trial carries no risk that’s a red flag, you know that’s not true. There is risk. Good researchers work hard to reduce the risk as much as possible, but you cannot eliminate it completely.”

She said even sites such as www.clinicaltrials.gov – a list of all the clinical trials registered with the National Institutes of Health – have to be approached cautiously and that you should talk to your own physican before signing up for anything.

Finally, UC San Diego’s Dr. Catriona Jamieson talked about her research into blood cancers, and how her work would not have been possible without the support of CIRM. She also highlighted the growing number of trials being carried out at through the CIRM Alpha Stem Cell Clinic Network, which helps scientists and researchers share knowledge and resources, enabling them to improve the quality of the care they provide patients.

The audience asked the panelists some great questions about the need for;

  • A national patient database to make it easier to recruit people for clinical trials
  • For researchers to create a way of letting people know if they didn’t get into a clinical trial so the patients wouldn’t get their hopes up
  • For greater public education about physicians or clinics offering unproven therapies

Adrienne Shapiro, an advocate for sickle cell disease patients, asks a question at Thursday’s stem cell meeting in La Jolla. (Bradley J. Fikes)

The meeting showed the tremendous public interest in stem cell research, and the desire to move it ahead even faster.

This was the first of a series of free public events we are holding around California this year. Next up, Los Angeles. More details of that shortly.

Stem Cell Stories That Caught Our Eye: Free Patient Advocate Event in San Diego, and new clues on how to fix muscular dystrophy and Huntington’s disease

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Stem cell research is advancing so fast that it’s sometimes hard to keep up. That’s one of the reasons we have our Friday roundup, to let you know about some fascinating research that came across our desk during the week that you might otherwise have missed.

Of course, another way to keep up with the latest in stem cell research is to join us for our free Patient Advocate Event at UC San Diego next Thursday, April 20th from 12-1pm.  We are going to talk about the progress being made in stem cell research, the problems we still face and need help in overcoming, and the prospects for the future.

We have four great speakers:

  • Catriona Jamieson, Director of the CIRM UC San Diego Alpha Stem Cell Clinic and an expert on cancers of the blood
  • Jonathan Thomas, PhD, JD, Chair of CIRM’s Board
  • Jennifer Briggs Braswell, Executive Director of the Sanford Stem Cell Clinical Center
  • David Higgins, Patient Advocate for Parkinson’s on the CIRM Board

We will give updates on the exciting work taking place at UCSD and the work that CIRM is funding. We have also set aside some time to get your thoughts on how we can improve the way we work and, of course, answer your questions.

What: Stem Cell Therapies and You: A Special Patient Advocate Event

When: Thursday, April 20th 12-1pm

Where: The Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037

Why: Because the people of California have a right to know how their money is helping change the face of regenerative medicine

Who: This event is FREE and open to everyone.

We have set up an EventBrite page for you to RSVP and let us know if you are coming. And, of course, feel free to share this with anyone you think might be interested.

This is the first of a series of similar Patient Advocate Update meetings we plan on holding around California this year. We’ll have news on other locations and dates shortly.

 

Fixing a mutation that causes muscular dystrophy (Karen Ring)

It’s easy to take things for granted. Take your muscles for instance. How often do you think about them? (Don’t answer this if you’re a body builder). Daily? Monthly? I honestly don’t think much about my muscles unless I’ve injured them or if they’re sore from working out.

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Heart muscle cells (green) that don’t have dystrophin protein (Photo; UT Southwestern)

But there are people in this world who think about their muscles or their lack of them every day. They are patients with a muscle wasting disease called Duchenne muscular dystrophy (DMD). It’s the most common type of muscular dystrophy, and it affects mainly young boys – causing their muscles to progressively weaken to the point where they cannot walk or breathe on their own.

DMD is caused by mutations in the dystrophin gene. These mutations prevent muscle cells from making dystrophin protein, which is essential for maintaining muscle structure. Scientists are using gene editing technologies to find and fix these mutations in hopes of curing patients of DMD.

Last year, we blogged about a few of these studies where different teams of scientists corrected dystrophin mutations using CRISPR/Cas9 gene editing technology in human cells and in mice with DMD. One of these teams has recently followed up with a new study that builds upon these earlier findings.

Scientists from UT Southwestern are using an alternative form of the CRISPR gene editing complex to fix dystrophin mutations in both human cells and mice. This alternative CRISPR complex makes use of a different cutting enzyme, Cpf1, in place of the more traditionally used Cas9 protein. It’s a smaller protein that the scientists say can get into muscle cells more easily. Cpf1 also differs from Cas9 in what DNA nucleotide sequences it recognizes and latches onto, making it a new tool in the gene editing toolbox for scientists targeting DMD mutations.

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Gene-edited heart muscle cells (green) that now express dystrophin protein (Photo: UT Southwestern)

Using CRISPR/Cpf1, the scientists corrected the most commonly found dystrophin mutation in human induced pluripotent stem cells derived from DMD patients. They matured these corrected stem cells into heart muscle cells in the lab and found that they expressed the dystrophin protein and functioned like normal heart cells in a dish. CRISPR/Cpf1 also corrected mutations in DMD mice, which rescued dystrophin expression in their muscle tissues and some of the muscle wasting symptoms caused by the disease.

Because the dystrophin gene is one of the longest genes in our genome, it has more locations where DMD-causing mutations could occur. The scientists behind this study believe that CRISPR/Cpf1 offers a more flexible tool for targeting different dystrophin mutations and could potentially be used to develop an effective gene therapy for DMD.

Senior author on the study, Dr. Eric Olson, provided this conclusion about their research in a news release by EurekAlert:

“CRISPR-Cpf1 gene-editing can be applied to a vast number of mutations in the dystrophin gene. Our goal is to permanently correct the underlying genetic causes of this terrible disease, and this research brings us closer to realizing that end.”

 

A cellular traffic jam is the culprit behind Huntington’s disease (Todd Dubnicoff)

Back in the 1983, the scientific community cheered the first ever mapping of a genetic disease to a specific area on a human chromosome which led to the isolation of the disease gene in 1993. That disease was Huntington’s, an inherited neurodegenerative disorder that typically strikes in a person’s thirties and leads to death about 10 to 15 years later. Because no effective therapy existed for the disease, this discovery of Huntingtin, as the gene was named, was seen as a critical step toward a better understand of Huntington’s and an eventual cure.

But flash forward to 2017 and researchers are still foggy on how mutations in the Huntingtin gene cause Huntington’s. New research, funded in part by CIRM, promises to clear some things up. The report, published this week in Neuron, establishes a connection between mutant Huntingtin and its impact on the transport of cell components between the nucleus and cytoplasm.

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The pores in the nuclear envelope allows proteins and molecules to pass between a cell’s nucleus and it’s cytoplasm. Image: Blausen.com staff (2014).

To function smoothly, a cell must be able to transport proteins and molecules in and out of the nucleus through holes called nuclear pores. The research team – a collaboration of scientists from Johns Hopkins University, the University of Florida and UC Irvine – found that in nerve cells, the mutant Huntingtin protein clumps up and plays havoc on the nuclear pore structure which leads to cell death. The study was performed in fly and mouse models of HD, in human HD brain samples as well as HD patient nerve cells derived with the induced pluripotent stem cell technique – all with this same finding.

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Huntington’s disease is caused by the loss of a nerve cells called medium spiny neurons. Image: Wikimedia commons

By artificially producing more of the proteins that make up the nuclear pores, the damaging effects caused by the mutant Huntingtin protein were reduced. Similar results were seen using drugs that help stabilize the nuclear pore structure. The implications of these results did not escape George Yohrling, a senior director at the Huntington’s Disease Society of America, who was not involved in the study. Yohrling told Baltimore Sun reporter Meredith Cohn:

“This is very exciting research because we didn’t know what mutant genes or proteins were doing in the body, and this points to new areas to target research. Scientists, biotech companies and pharmaceutical companies could capitalize on this and maybe develop therapies for this biological process”,

It’s important to temper that excitement with a reality check on how much work is still needed before the thought of clinical trials can begin. Researchers still don’t understand why the mutant protein only affects a specific type of nerve cells and it’s far from clear if these drugs would work or be safe to use in the context of the human brain.

Still, each new insight is one step in the march toward a cure.

You Are Invited: CIRM Patient Advocate Event, San Diego April 20th

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The word “cured” is one of the loveliest words in the English language. Last year we got to use it twice when we talked about stem cell therapies we are funding. Two of our clinical trials are not just helping people, they are curing them (you can read about that in our Annual Report).

But this was just part of the good news about stem cell research. We are making progress on many different fronts, against many different diseases, and we want to tell you all about that.

That’s why we are holding a special Patient Advocate event at UC San Diego on Thursday, April 20th from 12 – 1pm to talk about the progress being made in stem cell research, the problems we still face and need help in overcoming, and the prospects for the future.

We will have four terrific speakers:

  • Catriona Jamieson, Director of the CIRM UC San Diego Alpha Stem Cell Clinic and an expert on cancers of the blood
  • Jonathan Thomas, PhD, JD, Chair of CIRM’s Board
  • Jennifer Briggs Braswell, Executive Director of the Sanford Stem Cell Clinical Center
  • David Higgins, Patient Advocate for Parkinson’s on the CIRM Board

We will give updates on the exciting work taking place at UCSD and the work that CIRM is funding. We have also set aside some time to get your thoughts on how we can improve the way we work and, of course, answer your questions.

So we would love for you to join us, and tell your friends about the event as well. Here are the basic details.

What: Stem Cell Therapies and You: A Special Patient Advocate Event

When: Thursday, April 20th 12-1pm

Where: The Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037

Why: Because the people of California have a right to know how their money is helping change the face of regenerative medicine

Who: This event is FREE and open to the public

We have set up an EventBrite page for people to RSVP and let us know if they are coming.

We hope to see you there.

 

How do you know what patients want if you never even ask them?

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Our mission at CIRM is to accelerate stem treatments to patients with unmet medical needs. But what if those needs are not just unmet, they’re also unknown? What happens when those developing treatments never even bother to ask those they are trying to help if this is what they really need, or want?

The question came up during a panel discussion at a meeting of the CIRM Alpha Stem Cell Clinics Network in San Diego earlier this month. David Higgins, a CIRM Board member and a Patient Advocate for Parkinson’s disease, highlighted the problem saying that if you ask most people what they think is the biggest problem for Parkinson’s sufferers, they would probably say the movement disorders such as tremors and muscle rigidity. But David said that if you ask people who have Parkinson’s what their biggest problems are, then movement disorder probably wouldn’t even come in the top five concerns that they really have.

David listed insomnia, severe fatigue, anxiety, and depression as far more pressing and important:

“Researchers study what they know and they look to solve the things they think they can solve, and it is sometimes very different than the things that patients would like them to solve to ease their concerns.”

That sparked a fascinating discussion about the gap between what researchers and scientists sometimes think they should be doing, the kinds of treatments they should be trying to develop, and what the people who have those conditions really want.

David Parry, who is with GlaxoSmithKline and worked in drug development and discovery for most of his career, said:

“If I told you how many times I sat in meetings with my medical discovery group and talked about what our targets should be then we’d be here all night. We focus on what we know, what we think we can fix and what will work, when maybe we need to be more mindful of what could really make a difference in the life of patients.”

Alpha clinic panelAlpha Stem Cell Clinics Network panel discussion: Left David Higgins, David Parry, Catriona Jamieson, John Zaia, John Adams

Clearly there is a gap between what we think we can fix and what we should try and fix, and the best way to close that gap is to have a conversation.

Patients and Patient Advocates need to speak up and tell researchers what their main concerns and problems are, to help the scientists understand that while they would dearly love something that saves their life, they would also appreciate something that helps improve the quality of their lives.

Researchers too need to take a step back and not just get caught up in the search for an answer to a scientific or medical puzzle, without first asking “is this a puzzle that people want solved?”

At CIRM we work hard to make sure the voices of the patients and Patient Advocates are heard at every level of the work we do; from deciding what to fund to how to design a clinical trial involving our funding. But clearly it’s important that those voices be heard at a much earlier stage, to help shape the direction the research takes long before it comes to us for funding.

Breaking down barriers

For too long there has been a communications barrier between researchers and patients. This is not something that was deliberately constructed, it is something that simply evolved over time. Now it’s time to break down that barrier, and make sure both groups are talking to each other.

When it comes to developing treatments for deadly diseases and disorders, patients and researchers should think of themselves as partners. Researchers put their minds to work developing these treatments. Patients put their bodies on the line testing them.

Without the research there is no hope. Without the patients there is no proof. So, let’s start talking to each other.

If you have any thoughts or suggestions on how we can get this conversation started we would love to hear from you.

Patients are the Heroes at the CIRM Alpha Stem Cell Clinics Symposium

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UCSD’s Catriona Jamieson and patient advocate Sandra Dillon at the CIRM Alpha Clinic Network Symposium

Sometimes, when you take a moment to stand back and look at what you have accomplished, you can surprise yourself at how far you have come, and how much you have done in a short space of time.

Take the CIRM Alpha Stem Cell Clinics Network for example. In the 18 months since our Board invested $24 million to kick start the first three Alpha Clinics the Network has signed up 21 clinical trials. That’s no small achievement. But as far as the Alpha Clinics Network team is concerned, that’s just a start.

Alpha clinic table

Last week UC San Diego hosted the Second Annual CIRM Alpha Stem Cell Clinics Network Symposium. The gathering of scientists, medical staff and patient advocates spent a little time talking about the past, about what has been achieved so far, but most of the time was devoted to looking to the future, planning where they want to go and how they are going to get there.

The Network’s goal is to now dramatically increase the number of high quality stem cell clinical trials it is running, to make it even easier for companies and researchers looking for a site to carry out their trial, and to make it even easier for patients looking to sign up for one.

Alpha clinic panel

Panel at symposium: L to R: David Higgins, CIRM Board; David Parry, GSK; Catriona Jamieson, UCSD: John Zaia, City of Hope; John Adams, UCLA

For companies, the lure of having three Alpha Clinics (UC San Diego, City of Hope and the combined team of UCLA/UC Irvine) packed with skilled, experienced staff that specialize in delivering stem cell therapies is a big draw. (By the way, if you know anyone looking for funding for a clinical trial send them here).

The Alpha Clinic teams not only know how to deliver the therapies, they also know how to deliver patients. They spend a lot of time working with patients and patient advocates on the best ways to recruit people for trials, and the best way to design those trials so that they are as easy as possible for patients to take part in.

This attention to making it as good an experience for patients as possible starts from the very first time that a patient calls the clinics to find out if they are eligible for a trial. If there is no trial that is appropriate for that particular patient, the staff try to find an alternative trial at another location that might work.

Making sure it’s a good fit

If the Network does have a trial that meets the needs of the patient, then they begin the conversation to find out if the patient is eligible to apply. The goal of this part of the process is not simply to try and fill up available slots but to make sure that the patient is both a good match for the proposed therapy and that they also completely understand what’s involved in getting that therapy. For example, they need to understand if the trial involves staying overnight or several nights in the hospital, or if there are things they need to do ahead of time to prepare.

For the clinics themselves, one of the biggest challenges is insurance coverage. While the trial itself may be free, the patient may need to have some tests ahead of the treatment, to make sure they don’t have any underlying problems that could put their health at risk. The clinics need to know if the patient’s insurance will cover the cost of those tests and if they don’t what their options are. For a rare disease, where it’s challenging to find enough patients to produce meaningful results, these kinds of problems can jeopardize the whole trial.

The Alpha Clinics Network is working hard to develop answers to all of those problems, to create systems that make it as easy as possible to get a clinical trial up and running, and to recruit and keep patients in that trial.

Challenges to overcome

Part of the challenge is that many of these trials are for first-in-human therapies, meaning no one has ever tried this in a person before. That means the doctors, nurses and all the support staff in these clinics need to be specially trained in dealing with an entirely new way of treating people, with an entirely new class of therapies. And this isn’t just about technical skills. They also need to be good at communication, helping the patients understand everything that is happening or about to happen.

In a state like California, one of the most diverse places on earth, that’s no easy challenge. According to a UCLA study there are more than 220 languages spoken in LA County alone. Coping with that level of linguistic, cultural, and religious diversity is a challenge that the Alpha Clinics are working hard to meet.

Listening to patients

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Patient advocates were also an important voice at the symposium, talking about their experiences in clinical trials and how they have helped change their lives, and how they have, in some cases, saved their lives. But they also had some thoughts on how the researchers can do an even better job. That is the subject for a future blog.

While everyone acknowledged the challenges the CIRM Alpha Clinics face, they also celebrated what they have accomplished so far, and looked forward to the future. And the symposium was a chance to remind all of us that the reason we are in this is to help patients battling deadly diseases and disorders. So it was fitting that Thomas Kipps, the Deputy Director of Research at the UCSD Moore’s Cancer Center, took the opportunity to thank those who are not just the focus of this work, but also the heroes.

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Thomas Kipps: Photo courtesy Patient Power

“Clinical trials involve a very important skill set. You have to first and foremost put the patient first in any clinical trial. I think we cannot ignore the fact that these are human beings that are brave souls that have gone forward. These are the heroes who are going out and forging new territory.”