Stem Cell Agency Board Approves Three More Projects Targeting COVID-19

Dr. Jianhua Yu (left), Dr. Helen Blau (center), and Dr. Albert Wong (right)

The COVID-19 virus targets many different parts of the body, often with deadly or life-threatening consequences. This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investments in three early-stage research programs taking different approaches to battling the virus.

Dr. Jianhua Yu at the Beckman Research Institute of City of Hope was awarded $150,000 to use stem cells from umbilical cord blood to attack the virus. Dr. Yu and his team have many years of experience in taking cord blood cells and turning them into what are called chimeric antigen receptor (CAR) natural killer (NK) cells. The goal is to deploy these CAR NK cells to specifically target cells infected with COVID-19. This leverages the body of work at the City of Hope to develop this technology for cancer.

Dr. Helen Blau of Stanford University was awarded $149,996 to target recovery of muscle stem cells of the diaphragm in COVID-19 patients who have an extended period on a ventilator.

Patients with severe coronavirus often suffer respiratory failure and end up on mechanical ventilation that takes over the work of breathing. Over time, the diaphragm, the main muscle responsible for inhaling and exhaling, weakens and atrophies. There is no treatment for this kind of localized muscle wasting and it is anticipated that some of these patients will take months, if not years, to fully recover. Dr. Blau’s team proposes to develop a therapy with Prostaglandin E2 and Bupivacaine based on data generated by Dr. Blau’s group that these drugs, already approved by the FDA for other indications, have the potential to stimulate muscle stem cell recovery.

Dr. Albert Wong, also from Stanford University, was awarded $149,999 to develop vaccine candidates against COVID-19.

Most vaccine candidates are focused on getting the body to produce an antibody response to block the virus. However, Dr. Wong thinks that to be truly effective, a vaccine also needs to produce a CD8+ T cell response to augment an effective immune response to remove the COVID-19 infected cells that are hijacked by the virus to spread and cause illness.  This team will use the experience it gained using CIRM funds to vaccine against glioblastoma, a deadly brain cancer, to advance a similar approach to produce an effective cellular immune response to combat COVID-19.  

“CIRM is committed to supporting novel, multi-pronged approaches to battle this COVID-19 crisis that leverage solid science and knowledge gained in other areas.” says Dr. Maria T. Millan, the President & CEO of CIRM. “These three projects highlight three very different approaches to combatting the acute devastating health manifestations of COVID-19 as well as the debilitating sequelae that impact the ability to recover from the acute illness. Through this COVID funding opportunity, CIRM is enabling researchers to re-direct work they have already done, often with CIRM support, to quickly develop new approaches to COVID-19.”

Two UCLA scientists receive CIRM funding for discovery research for COVID-19

Dr. Brigitte Gomperts (left) and Dr. Gay Crooks (right), UCLA
Image Credit: UCLA Broad Stem Cell Center

This past Friday, the CIRM Board approved funding for its first clinical study for COVID-19. In addition to this, the Board also approved two discovery stage research projects, which support promising new technologies that could be translated to enable broad use and improve patient care. Before we go into more detail, the two awards are summarized in the table below:

The discovery grant for $150,000 was given to Dr. Gay Crooks at UCLA to study how specific immune cells called T cells respond to COVID-19. The goal of this is to inform the development of vaccines and therapies that harness T cells to fight the virus. Typically, vaccine research involves studying the immune response using cells taken from infected people. However, Dr. Crooks and her team are taking T cells from healthy people and using them to mount strong immune responses to parts of the virus in the lab. They will then study the T cells’ responses in order to better understand how T cells recognize and eliminate the virus.

This method uses blood forming stem cells and then converts them into specialized immune cells called dendritic cells, which are able to devour proteins from viruses and chop them into fragments, triggering an immune response to the virus.

In a press release from UCLA, Dr. Crooks says that, “The dendritic cells we are able to make using this process are really good at chopping up the virus, and therefore eliciting a strong immune response”

The discovery grant for $149,998 was given to Dr. Brigitte Gomberts at UCLA to study a lung organoid model made from human stem cells in order to identify drugs that can reduce the number of infected cells and prevent damage in the lungs of patients with COVID-19. Dr. Gomberts will be testing drugs that have been approved by the U.S. Food and Drug Administration (FDA) for other purposes or have been found to be safe in humans in early clinical trials. This increases the likelihood that if a successful drug is found, it can be approved more rapidly for widespread use.

In the same press release from UCLA, Dr. Gomberts discusses the potential drugs they are evaluating.

“We’re starting with drugs that have already been tested in humans because our goal is to find a therapy that can treat patients with COVID-19 as soon as possible.”

CIRM Board Funds its First Clinical Study for COVID-19

Dr. John Zaia, City of hope

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) continued its commitment to help with the coronavirus pandemic by awarding $749,999 to Dr. John Zaia at City of Hope.  He will be conducting a clinical study to administer blood plasma from recovered COVID-19 patients to treat those with the virus.  This marks CIRM’s first clinical study for COVID-19 after approving emergency funding a month earlier.

Plasma is a component of blood that carries proteins called antibodies that are usually involved in defending our bodies against viral infections.  Blood plasma from patients that have recovered from COVID-19, referred to as convalescent plasma, contain antibodies against the virus that can be used as a potential treatment for COVID-19.  Currently, there are challenges with this approach that include: properly identifying convalescent plasma donors i.e. recovered patients, determining eligibility of those with convalescent plasma that want to donate, collection of the plasma, treating patients, and determining if the plasma was effective.

Dr. Zaia and his team at City of Hope will create the COVID-19 Coordination Program, which addresses solutions for all of the challenges listed above. The program will partner with the medical teams at CIRM’s Alpha Stem Cell Clinic Network, as well as infectious disease, pulmonary and critical care teams from medical centers and community hospitals across the state.  Potential donors will be identified and thoroughly screened for eligibility per the established National and State blood banking safety requirements. Finally, the convalescent plasma will be collected from eligible donors and administered by licensed physicians to COVID-19 patients, who will be evaluated for response to the treatment and potential recovery.

“We are in the midst of very challenging times where there is not yet an approved treatment for COVID-19. In response to this, CIRM launched and executed an emergency COVID-19 funding program, which was made possible by our Board, patient advocates, California scientists, external scientific expert reviewers, and our dedicated team,” said Maria T. Millan, MD, President and CEO of CIRM. “With CIRM funding, the City of Hope COVID-19 Coordination program will tap into CIRM’s network of researchers, physicians, and our Alpha Clinics to deliver this treatment to patients in need.  It will also serve the critical role of gathering important scientific data about the plasma, safety, and clinical data from treated patients.”

The Board also approved a discovery stage research project that utilizes stem cell models for a novel approach to vaccine development against the virus causing COVID-19 and another project that uses a unique lung stem cell organoid to identify an effective drug against the virus.

The two awards are summarized in the table below:

Breaking bad news to stem cell researchers

It’s never easy to tell someone that they are too late, that they missed the deadline. It’s particularly hard when you know that the person you are telling that to has spent years working on a project and now needs money to take it to the next level. But in science, as in life, it’s always better to tell people what they need to know rather than what they would like to hear.

And so, we have posted a notice on our website for researchers thinking about applying for funding that, except in a very few cases, they are too late, that there is no money available for new projects, whether it’s Discovery, Translational or Clinical.

Here’s that notice:

CIRM anticipates that the budget allocation of funds for new awards under the CIRM clinical program (CLIN1, CLIN2 and CLIN3) may be depleted within the next two to three months. CIRM will accept applications for the monthly deadline on June 28, 2019 but will suspend application submissions after that date until further notice. All applicants should note that the review of submitted applications may be halted at any point in the process if funds are depleted prior to completion of the 3-month review cycle. CIRM will notify applicants of such an occurrence. Therefore, submission and acceptance of an application to CIRM does not guarantee the availability of funds or completion of a review cycle.

The submission of applications for the CIRM/NHLBI Cure Sickle Cell Initiative (CLIN1 SCD, CLIN2 SCD) are unaffected and application submissions for this program will remain open.

We do, of course, have enough money set aside to continue funding all the projects our Board has already approved, but we don’t have money for new projects (except for some sickle cell disease projects).

In truth our funding has lasted a lot longer than anyone anticipated. When Proposition 71 was approved the plan was to give CIRM $300 million a year for ten years. That was back in 2004. So what happened?

Well, in the early years stem cell science was still very much in its infancy with most of the work being done at a basic or Discovery level. Those typically don’t require very large sums so we were able to fund many projects without hitting our $300m target. As the field progressed, however, more and more projects were at the clinical trial stage and those need multiple millions of dollars to be completed. So, the money went out faster.

To date we have funded 55 clinical trials and our early support has helped more than a dozen other projects get into clinical trials. This includes everything from cancer and stroke, to vision loss and diabetes. It’s a good start, but we feel there is so much more to do.

Followers of news about CIRM know there is talk about a possible ballot initiative next year that would provide another $5.5 billion in funding for us to help complete the mission we have started.

Over the years we have built a pipeline of promising projects and without continued support many of those projects face a difficult future. Funding at the federal level is under threat and without CIRM there will be a limited number of funding alternatives for them to turn to.

Telling researchers we don’t have any money to support their work is hard. Telling patients we don’t have any money to support work that could lead to new treatments for them, that’s hardest of all.

Celebrating Exciting CIRM-Funded Discovery Research on World Parkinson’s Day

April 11th is World Parkinson’s Disease Awareness Day. To mark the occasion, we’re featuring the work of CIRM-funded researchers who are pursuing new, promising ideas to treat patients with this debilitating neurodegenerative disease.


Birgitt Schuele, Parkinson’s Institute

CIRM Grant: Quest Award – Discovery Stage Research

Research: Birgitt and her team at the Parkinson’s Institute in Sunnyvale, California, are using CRISPR gene editing technology to reduce the levels of a toxic protein called alpha synuclein, which builds up in the dopaminergic brain cells affected by Parkinson’s disease.

Birgitt Schuele

“My hope is that I can contribute to stopping disease progression in Parkinson’s. If we can develop a drug that can get rid of accumulated protein in someone’s brain that should stop the cells from dying. If someone has early onset PD and a slight tremor and minor walking problems, stopping the disease and having a low dose of dopamine therapy to control symptoms is almost a cure.”

Parkinson’s disease in a dish. Dopaminergic neurons made from Parkinson’s patient induced pluripotent stem cells. (Image credit: Birgitt Schuele)


Jeanne Loring, Scripps Research Institute

CIRM Grant: Quest Award – Discovery Stage Research

Research: Jeanne Loring and her team at the Scripps Research Institute in La Jolla, California, are deriving dopaminergic neurons from the iPSCs of Parkinson’s patients. Their goal is to develop a personalized, stem cell-based therapy for PD.

Jeanne Loring

“We are working toward a patient-specific neuron replacement therapy for Parkinson’s disease.  By the time PD is diagnosed, people have lost more than half of their dopamine neurons in a specific part of the brain, and loss continues over time.  No drug can stop the loss or restore the neurons’ function, so the best possible option for long term relief of symptoms is to replace the dopamine neurons that have died.  We do this by making induced pluripotent stem cells from individual PD patients and turning them into the exact type of dopamine neuron that has been lost.  By transplanting a patient’s own cells, we will not need to use potentially dangerous immunosuppressive drugs.  We plan to begin treating patients in a year to two years, after we are granted FDA approval for the clinical therapy.”

Skin cells from a Parkinson’s patient (left) were reprogrammed into induced pluripotent stem cells (center) that were matured into dopaminergic neurons (right) to model Parkinson’s disease. (Image credit: Jeanne Loring)


Justin Cooper-White, Scaled BioLabs Inc.

CIRM Grant: Quest Award – Discovery Stage Research

Research: Justin Cooper-White and his team at Scaled Biolabs in San Francisco are developing a tool that will make clinical-grade dopaminergic neurons from the iPSCs of PD patients in a rapid and cost-effective manner.

Justin Cooper-White

“Treating Parkinson’s disease with iPSC-derived dopaminergic neuron transplantation has a strong scientific and clinical rationale. Even the best protocols are long and complex and generally have highly variable quality and yield of dopaminergic neurons. Scaled Biolabs has developed a technology platform based on high throughput microfluidics, automation, and deep data which can optimize and simplify the road from iPSC to dopaminergic neuron, making it more efficient and allowing a rapid transition to GMP-grade derivation of these cells.  In our first 6 months of CIRM-funded work, we believe we have already accelerated and simplified the production of a key intermediate progenitor population, increasing the purity from the currently reported 40-60% to more than 90%. The ultimate goal of this work is to get dopaminergic neurons to the clinic in a robust and economical manner and accelerate treatment for Parkinson’s patients.”

High throughput differentiation of dopaminergic neuron progenitors in  microbioreactor chambers in Scaled Biolabs’ cell optimization platform. Different chambers receive different differentiation factors, so that optimal treatments for conversion to dual-positive cells can be determined (blue: nuclei, red: FOXA2, green: LMX1A).


Xinnan Wang, Stanford University

CIRM Grant: Basic Biology V

Research: Xinnan Wang and her team at Stanford University are studying the role of mitochondrial dysfunction in the brain cells affected in Parkinson’s disease.

Xinnan Wang

“Mitochondria are a cell’s power plants that provide almost all the energy a cell needs. When these cellular power plants are damaged by stressful factors present in aging neurons, they release toxins (reactive oxygen species) to the rest of the neuron that can cause neuronal cell death (neurodegeneration).  We hypothesized that in Parkinson’s mutant neurons, mitochondrial quality control is impaired thereby leading to neurodegeneration. We aimed to test this hypothesis using neurons directly derived from Parkinson’s patients (induced pluripotent stem cell-derived neurons).”

Dopaminergic neurons derived from human iPSCs shown in green, yellow and red. (Image credit: Atossa Shaltouki, Stanford)


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Budgeting for the future of the stem cell agency

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The CIRM Board discusses the future of the Stem Cell Agency

Budgets are very rarely exciting things; but they are important. For example, it’s useful for a family to know when they go shopping exactly how much money they have so they know how much they can afford to spend. Stem cell agencies face the same constraints; you can’t spend more than you have. Last week the CIRM Board looked at what we have in the bank, and set us on a course to be able to do as many of the things we want to, with the money we have left.

First some context. Last year CIRM spent a shade over $306 million on a wide range of research from Discovery, the earliest stage, through Translational and into Clinical trials. We estimate that is going to leave us with approximately $335 million to spend in the coming years.

A couple of years ago our Board approved a 5 year Strategic Plan that laid out some pretty ambitious goals for us to achieve – such as funding 50 new clinical trials. At the time, that many clinical trials definitely felt like a stretch and we questioned if it would be possible. We’re proving that it is. In just two years we have funded 26 new clinical trials, so we are halfway to our goal, which is terrific. But it also means we are in danger of using up all our money faster than anticipated, and not having the time to meet all our goals.

Doing the math

So, for the last couple of months our Leadership Team has been crunching the numbers and looking for ways to use the money in the most effective and efficient way. Last week they presented their plan to the Board.

It boiled down to a few options.

  • Keep funding at the current rate and run out of money by 2019
  • Limit funding just to clinical trials, which would mean we could hit our 50 clinical trial goal by 2020 but would not have enough to fund Discovery and Translational level research
  • Place caps on how much we fund each clinical trial, enabling us to fund more clinical trials while having enough left over for Discovery and Translational awards

The Board went for the third option for some good reasons. The plan is consistent with the goals laid out in our Strategic Plan and it supports Discovery and Translational research, which are important elements in our drive to develop new therapies for patients.

Finding the right size cap

Here’s a look at the size of the caps on clinical trial funding. You’ll see that in the case of late stage pre-clinical work and Phase 1 clinical trials, the caps are still larger than the average amount we funded those stages last year. For Phase 2 the cap is almost the same as the average. For Phase 3 the cap is half the amount from last year, but we think at this stage Phase 3 trials should be better able to attract funding from other sources, such as industry or private investors.

cap awards

Another important reason why the Board chose option three – and here you’ll have to forgive me for being rather selfish – is that it means the Administration Budget (which pays the salaries of the CIRM team, including yours truly) will be enough to cover the cost of running this research plan until 2020.

The bottom line is that for 2018 we’ll be able to spend $130 million on clinical stage research, $30 million for Translational stage, and $10 million for Discovery. The impact the new funding caps will have on clinical stage projects is likely to be small (you can see the whole presentation and details of our plan here) but the freedom it gives us to support the broad range of our work is huge.

And here is where to go if you are interested in seeing the different funding opportunities at CIRM.

Getting faster, working smarter: how changing the way we work is paying big dividends

This blog is part of the Month of CIRM series

Speeding up the way you do things isn’t always a good idea. Just ask someone who got a ticket for going 65mph in a 30mph zone. But at CIRM we have found that doing things at an accelerated pace is paying off in a big way.

When CIRM started back in 2004 we were, in many ways, a unique organization. That meant we pretty much had to build everything from scratch, creating our own ways of asking for applications, reviewing those applications, funding them etc. Fast forward ten years and it was clear that, as good a job as we did in those early days, there was room for improvement in the way we operated.

So we made some changes. Big changes.

We adopted as our mantra the phrase “operational excellence.” It doesn’t exactly trip off the tongue but it does reflect what we were aiming for. The Business Dictionary defines operational excellence as:

 “A philosophy of the workplace where problem-solving, teamwork, and leadership results in the ongoing improvement in an organization.”

We didn’t want to just tinker with the way we worked, we wanted to reinvent every aspect of our operation. To do that we involved everyone in the operation. We held a series of meetings where everyone at CIRM, and I do mean everyone, was invited to join in and offer their ideas on how to improve our operation.

CIRM2.0_Logo

The end result was CIRM 2.0. At the time we described it as “a radical overhaul” of the way we worked. That might have been an understatement. We increased the speed, frequency and volume of the programs we offered, making it easier and more predictable for researchers to apply to us for funding, and faster for them to get that funding if they were approved.

For example, before 2.0 it took almost two years to go from applying for funding for a clinical trial to actually getting that funding. Today it takes around 120 days.

But it’s not just about speed. It’s also about working smarter. In the past if a researcher’s application for funding for a clinical trial failed it could be another 12 months before they got a chance to apply again. With many diseases 12 months could be a death sentence. So we changed the rules. Now if you have a project ready for a clinical trial you can apply any time. And instead of recommending or not recommending a project, basically voting it up or down, our independent panel of expert reviewers now give researchers with good but not great applications constructive feedback, enabling the researchers to make the changes needed to improve their project, and reapply for funding within 30 days.

This has not only increased the number of applications for clinical trials, it has also increased the quality of those applications.

We made similar changes in our Discovery and Translation programs. Increasing the frequency of each award, making it easier for researchers to know when the next round of funding was coming up. And we added incentives to encourage researchers to move successful projects on to the next level. We wanted to create a pipeline of the most promising projects steadily moving towards the clinic.

The motivation to do this comes from our patients. At CIRM we are in the time business. Many of the patients who are looking to stem cells to help them don’t have the luxury of time; they are rapidly running out of it. So we have a responsibility to do all we can to reduce the amount of time it takes to get the most promising therapies to them, without in any way compromising safety and jeopardizing their health.

By the end of 2016 those changes were very clearly paying dividends as we increased the frequency of reviews and the number of projects we reviewed but at the same time decreased the amount of time it took us to do all that.

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But we are not done yet. We have done a good job of improving the way we work. But there is always room to be even better, to go even faster and be more efficient.

We are not done accelerating. Not by a long shot.

How Parkinson’s disease became personal for one stem cell researcher

April is Parkinson’s disease Awareness Month. This year the date is particularly significant because 2017 is the 200th anniversary of the publication of British apothecary James Parkinson’s “An Essay on the Shaking Palsy”, which is now recognized as a seminal work in describing the disease.

Schuele_headshotTo mark the occasion we talked with Dr. Birgitt Schuele, Director Gene Discovery and Stem Cell Modeling at the Parkinson’s Institute and Clinical Center in Sunnyvale, California. Dr. Schuele recently received funding from CIRM for a project using new gene-editing technology to try and halt the progression of Parkinson’s.

 

 

What got you interested in Parkinson’s research?

People ask if I have family members with Parkinson’s because a lot of people get into this research because of a family connection, but I don’t.  I was always excited by neuroscience and how the brain works, and I did my medical residency in neurology and had a great mentor who specialized in the neurogenetics of Parkinson’s. That helped fuel my interest in this area.

I have been in this field for 15 years, and over time I have gotten to know a lot of people with Parkinson’s and they have become my friends, so now I’m trying to find answers and also a cure for Parkinson’s. For me this has become personal.

I have patients that I talk to every couple of months and I can see how their disease is progressing, and especially for people with early or young onset Parkinson’s. It’s devastating. It has a huge effect on the person and their family, and on relationships, even how they have to talk to their kids about their risk of getting the disease themselves. It’s hard to see that and the impact it has on people’s lives. And because Parkinson’s is progressive, I get to see, over the years, how it affects people, it’s very hard.

Talk about the project you are doing that CIRM is funding

It’s very exciting. The question for Parkinson’s is how do you stop disease progression, how do you stop the neurons from dying in areas affected by the disease. One protein, identified in 1997 as a genetic form of Parkinson’s, is alpha-synuclein. We know from studying families that have Parkinson’s that if you have too much alpha-synuclein you get early onset, a really aggressive form of Parkinson’s.

I followed a family that carries four copies of this alpha-synuclein gene (two copies is the normal figure) and the age of onset in this family was in their mid 30’s. Last year I went to a funeral for one of these family members who died from Parkinson’s at age 50.

We know that this protein is bad for you, if you have too much it kills brains cells. So we have an idea that if you lower levels of this protein it might be an approach to stop or shield those cells from cell death.

We are using CRISPR gene editing technology to approach this. In the Parkinson’s field this idea of down-regulation of alpha-synuclein protein isn’t new, but previous approaches worked at the protein level, trying to get rid of it by using, for example, immunotherapy. But instead of attacking the protein after it has been produced we are starting at the genomic level. We want to use CRISPR as a way to down-regulate the expression of the protein, in the same way we use a light dimmer to lower the level of light in a room.

But this is a balancing act. Too much of the protein is bad, but so is too little. We know if you get rid of the protein altogether you get negative effects, you cause complications. So we want to find the right level and that’s complex because the right level might vary from person to person.

We are starting with the most extreme levels, with people who have twice as much of this protein as is normal. Once we understand that better, then we can look at people who have levels that are still higher than normal but not at the upper levels we see in early-onset Parkinson’s. They have more subtle changes in their production or expression of this protein. It’s a little bit of a juggling act and it might be different for different patients. We start with the most severe ones and work our way to the most common ones.

One of the frustrations I often hear from patients is that this is all taking so long. Why is that?

Parkinson’s has been overall frustrating for researchers as well. Around 100 years ago, Dr. Lewy first described the protein deposits and the main neuropathology in Parkinson’s. About 20 years ago, mutations in the alpha-synuclein gene were discovered, and now we know approximately 30 genes that are associated with, or can cause Parkinson’s. But it was all very descriptive. It told us what is going on but not why.

Maybe we thought it was straight forward and maybe researchers only focused on what we knew at that point. In 1957, the neurotransmitter dopamine was identified and since the 1960s people have focused on Parkinson’s as a dopamine-deficient problem because we saw the amazing effects L-Dopa had on patients and how it could help ease their symptoms.

But I would say in the last 15 years we have looked at it more closely and realized it’s more complicated than that. There’s also a loss of sense of smell, there’s insomnia, episodes of depression, and other things that are not physical symptoms. In the last 10 years or so we have really put the pieces together and now see Parkinson’s as a multi-system disease with neuronal cell death and specific protein deposits called Lewy Bodies. These Lewy Bodies contain alpha-synuclein and you find them in the brain, the gut and the heart and these are organs people hadn’t looked at because no one made the connection that constipation or depression could be linked to the disease. It turns out that Parkinson’s is much more complicated than just a problem in one particular region of the brain.

The other reason for slow progress is that we don’t have really good models for the disease that are predictive for clinical outcomes. This is why probably many clinical trials in the neurodegenerative field have failed to date. Now we have human induced pluripotent stem cells (iPSCs) from people with Parkinson’s, and iPSC-derived neurons allow us to better model the disease in the lab, and understand its underlying mechanisms  more deeply. The technology has now advanced so that the ability to differentiate these cells into nerve cells is better, so that you now have iPSC-derived neurons in a dish that are functionally active, and that act and behave like dopamine-producing neurons in the brain. This is an important advance.

Will this lead to a clinical trial?

That’s the idea, that’s our hope.

We are working with professor Dr. Deniz Kirik at the University of Lund in Sweden. He’s an expert in the field of viral vectors that can be used in humans – it’s a joint grant between us – and so what we learn from the human iPS cultures, he’ll transfer to an animal model and use his gene vector technology to see if we can see the same effects in vivo, in mice.

We are using a very special Parkinson’s mouse model – developed at UC San Francisco – that has the complete human genomic structure of the alpha-synuclein gene. If all goes well, we hope that ultimately we could be ready in a couple of years to think about preclinical testing and then clinical trials.

What are your hopes for the future?

My hope is that I can contribute to stopping disease progression in Parkinson’s. If we can develop a drug that can get rid of accumulated protein in someone’s brain that should stop the cells from dying. If someone has early onset PD and a slight tremor and minor walking problems, stopping the disease and having a low dose of dopamine therapy to control symptoms is almost a cure.

The next step is to develop better biomarkers to identify people at risk of developing Parkinson’s, so if you know someone is a few years away from developing symptoms, and you have the tools in place, you can start treatment early and stop the disease from kicking in, even before you clinically have symptoms.

Thinking about people who have been diagnosed with a disease, who are ten years into the disease, who already have side effects from the disease, it’s a little harder to think of regenerative medicine, using embryonic or iPSCs for this. I think that it will take longer to see results with this approach, but that’s the long-term hope for the future. There are many  groups working in this space, which is critical to advance the field.

Why is Parkinson’s Awareness Month important?

It’s important because, while a lot of people know about the disease, there are also a lot of misconceptions about Parkinson’s.

Parkinson’s is confused with Alzheimer’s or dementia and cognitive problems, especially the fact that it’s more than just a gait and movement problem, that it affects many other parts of the body too.

New stem cell could offer new ways to study birth defects

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Tony Parenti, MSU Ph.D student in cell and molecular biology

You never know what you are going to find in the trash. For a group of intrepid researchers at Michigan State University their discovery could lead to new ways of studying birth defects and other reproductive problems. Because what they found in what’s normally considered cellular trash was a new kind of stem cell.

The cell is called an induced extraembryonic endoderm stem (iXEN) cell. The team’s findings are reported in the journal Stem Cell Reports and here’s how lead author Tony Parenti described what they found:

“Other scientists may have seen these cells before, but they were considered to be defective, or cancer-like. Rather than ignore these cells that have been mislabeled as waste byproducts, we found gold in the garbage.”

Here’s the backstory to this discovery. For years researchers have considered embryonic stem cells as the “gold standard” for pluripotent cells, the kind that can be differentiated, or changed, into all kinds of cell in the body.

But studies in mice show that in addition to creating these pluripotent stem cells, the mouse embryo also produces extraembryonic endoderm or XEN cells. For a long time it was believed the gene expression of XEN cells affected the pluripotent stem cells, but the XEN cells were usually thought to be cancer-like, something that occurred as a byproduct of the developing embryo.

Searching through the trash

And that’s how things stayed until the research team at MSU noticed a bunch of XEN-like cells showing up every time they created induced pluripotent stem (iPS) cells – a kind of man-made equivalent of embryonic cells with the ability to turn into any other kind of cell but derived in a different way, reprogrammed from adult cells.

So they set out to see how important these, what they called induced or iXEN, cells were to the development of iPS cells. The researchers took  adult mouse cells and reprogrammed them into iPS cells and noticed colonies of iXEN cells in these cultures.

The first goal was to make sure these iXEN cells weren’t cancer-causing, as many researchers believed. This took six months but at the end of it not only were they able to demonstrate that the cells aren’t cancer-causing in a cell culture dish, but that they are a new type of stem cell.

Next step was to see how important endodermal genes are in the formation of iXEN cells. They found that decreasing endodermal gene expression led to a two-fold decrease in the number of iXEN cells and a significant increase in the number of iPS cells.

Competitors not collaborators

They concluded that the parallel pathways that generate pluripotent and XEN cells are in competition with each other and not in support of each other during reprogramming. By suppressing one they were able to boost the other. To their delight they had stumbled on a more efficient way of creating iPS cells.

While the discovery of a new kind of stem cell is always exciting there’s a catch to this; we still don’t know if XEN cells are found in humans. But this discovery gives the researchers additional tools to try and find the answer to that question.

Amy Ralston, a co-author of the study, said in a news release:

“It’s a missing tool that we don’t have yet. It’s true that XEN cells have characteristics that pluripotent stem cells do not have. Because of those traits, iXEN cells can shed light on reproductive diseases. If we can continue to unlock the secrets of iXEN cells, we may be able to improve induced pluripotent stem cell quality and lay the groundwork for future research on tissues that protect and nourish the human embryo.”

Normally the discovery of anything new, particularly when it over turns a long-held belief, is met with a degree of healthy skepticism at first. In science that’s a good thing. We all remember the eager way that STAP stem cells were hailed by many as a new way to create pluripotent stem cells until the research was discredited. But so far the Twitterverse and media outlets seems to share in the excitement about this discovery.

If you want to accelerate stem cell therapies then create an Accelerating Center

Buckle up

Buckle up, we’re about to Accelerate

“You can’t teach fish to fly,” is one of the phrases that our CIRM President & CEO, Randy Mills, likes to throw out when asked why we needed to create new centers to help researchers move their most promising therapies out of the lab and into clinical trials.

His point is that many researchers are terrific at research but not so great at the form filling and other process-oriented skills needed to get approval from the Food and Drug Administration (FDA) for a clinical trial.

So instead of asking them to learn how to do all those things, why don’t we, CIRM, create a system that will do it for them? And that’s where we came up with the idea for the Accelerating Center (we’re also creating a Translating Center – that’s a topic for a future blog but if you can’t wait to find out the juicy details you can find them here.)

The Accelerating Center will be a clinical research organization that provides regulatory, operational and other support services to researchers and companies hoping to get their stem cell therapies into a clinical trial. The goal is to match the scientific skills of researchers with the regulatory and procedural skills of the Accelerating Center to move these projects through the review process as quickly as possible.

But it doesn’t end there. Once a project has been given the green light by the FDA, the Accelerating Center will help with actually setting up and running their clinical trial, and helping them with data management to ensure they get high quality data from the trial. Again these skills are essential to run a good clinical trial but things researchers may not have learned about when getting a PhD.

We just issued what we call an RFA (Request for Applications)  for people interested in partnering with us to help create the Accelerating Center. To kick-start the process we are awarding up to $15 million for five years to create the Center, which will be based in California.

To begin with, the Accelerating Center will focus on supporting CIRM-funded stem cell projects. But the goal is to eventually extend that support to other stem cell programs.

Now, to be honest, there’s an element of self-interest in all this. We have a goal under our new Strategic Plan of funding 50 new clinical trials over the next five years. Right now, getting a stem cell-related project approved is a slow and challenging process. We think the Accelerating Center is one tool to help us change that and give the most promising projects the support they need to get out of the lab and into people.

There’s a lot more we want to do to help speed up the approval process as well, including working with the FDA to create a new, streamlined regulatory process, one that is faster and easier to navigate. But that may take some time. So in the meantime, the Accelerating Center will help “fish” to do what they do best, swim, and we’ll take care of the flying for them.