Improving process drives progress in stem cell research

shutterstock_212888935Process is not a sexy word. No one gets excited thinking about improving a process. Yet behind every great idea, behind every truly effective program is someone who figured out a way to improve the process, to make that idea not just work, but work better.

It’s not glamorous. Sometimes it’s not even pretty. But it is essential.

Yesterday in Oakland our governing Board approved two new concepts to improve our process, to help us fund research in a way that is faster, smarter and ultimately helps us better meet our mission of accelerating the development of stem cell therapies for patients with unmet medical needs.

The new concepts are for Discovery – the earliest stage of research – and the Translational phase, a critical step in moving promising therapies out of the lab and toward clinical trials where they can be tested in people.

In a news release C. Randal Mills, Ph.D., CIRM’s President and CEO, said that these additions built on the work started when the agency launched CIRM 2.0 in January for the clinical phase of research:

“What makes this approach different is that under CIRM 2.0 we are creating a pathway for research, from Discovery to Translational and Clinical, so that if a scientist is successful with their research at one level they are able to move that ahead into the next phase. We are not interested in research just for its own sake. We are interested in research that is going to help us help patients.”

In the Discovery program, for example, we will now be able to offer financial incentives to encourage researchers who successfully complete their work to move it along into the Translational phase – either themselves or by finding a scientific partner willing to take it up and move it forward.

This does a number of things. First it helps create a pipeline for the most promising projects so ideas that in the past might have stopped once the initial study ended now have a chance to move forward. Obviously our hope is that this forward movement will ultimately lead to a clinical trial. That won’t happen with every research program we fund but this approach will certainly increase the possibility that it might.

There’s another advantage too. By scheduling the Discovery and Translational awards more regularly we are creating a grant system that has more predictability, making it easier for researchers to know when they can apply for funding.

We estimate that each year there will be up to 50 Discovery awards worth a total of $53 million; 12 Translation awards worth a total of $40 million; and 12 clinical awards worth around $100 million. That’s a total of more than $190 million every year for research.

This has an important advantage for the stem cell agency too. We have close to $1 billion left in the bank so we want to make sure we spend it as wisely as we can.

As Jonathan Thomas, Ph.D. J.D, the Chair of our Board, said, having this kind of plan helps us better plan our financial future;

“Knowing how often these programs are going to be offered, and how much money is likely to be awarded means the Board has more information to work with in making decisions on where best to allocate our funding.”

The Board also renewed funding for both the Bridges and SPARK (formerly Creativity) programs. These are educational and training programs aimed at developing the next generation of stem cell scientists. The Bridges students are undergraduate or Master’s level students. The SPARK students are all still in high school. Many in both groups come from poor or low-income communities. This program gives them a chance to work in a world-class stem cell research facility and to think about a career in science, something that for many might have been unthinkable without Bridges or SPARK.

Process isn’t pretty. But for the students who can now think about becoming a scientist, for the researchers who can plan new studies, and for the patients who can now envision a potential therapy getting into clinical trials, that process can make all the difference.

Pushing, pulling and dragging stem cell research forward

Government agencies are known for many things, but generally speaking a willingness to do some voluntary, deep self-examination is not one of them. However, for the last few weeks CIRM has been doing a lot of introspection as we develop a new Strategic Plan, a kind of road map for where we are heading.

Patient Advocate meeting in Los Angeles: Photo courtesy Cristy Lytal USC

Patient Advocate meeting in Los Angeles:
Photo courtesy Cristy Lytal USC

But we haven’t been alone. We’ve gone to San Diego, Los Angeles and San Francisco to talk to Patient Advocates in each city, to get their thoughts on what we need to focus on for the future. Why Patient Advocates? Because they are the ones with most skin in the game. They are why we do this work so it’s important they have a say in how we do it.

As Chris Stiehl, a Patient Advocate for type 1 diabetes, said in San Diego: “Let the patient be in the room, let them be part of the conversation about these therapies. They are the ones in need, so let them help make decisions about them right from the start, not at the end.”

A Strategic Plan is, on the surface, a pretty straightforward thing to put together. You look at where you are, identify where you want to go, and figure out the best way to get from here to there. But as with many things, what seems simple on the surface often turns out to be a lot more complicated when looked at in more depth.

The second bit, figuring out where you want to go, is easy. We want to live up to our mission of accelerating the development of stem cells therapies to patients with unmet medical needs. We don’t want to be good at this. We want to be great at this.

Dr. C. Randal Mills talking to Patient Advocates in LA: Photo courtesy Cristy Lytal, USC

Dr. C. Randal Mills talking to Patient Advocates in LA: Photo courtesy Cristy Lytal, USC

The first part, seeing where you are, is a little tougher: it involves what our President and CEO, Dr. Randy Mills, “confronting some brutal facts”, being really honest in assessing where you are because without that honesty you can’t achieve anything.

So where are we as an agency? Well, we have close to one billion dollars left in the bank, we have 12 projects in clinical trials and more on the way, we have helped advance stem cells from a fledgling field to a science on the brink of what we hope will be some remarkable treatments, and we have a remarkable team ready to help drive the field still further.

But how do we do that, how do we identify the third part of the puzzle, getting from where we are to where we want to be? CIRM 2.0 is part of the answer – developing a process to fund research that is easier, faster and more responsive to the needs of the scientists and companies developing new therapies. But that’s just part of the answer.

Some of the Patient Advocates asked if we considered focusing on just a few diseases, such as the ten largest killers of Americans, and devoting our remaining resources to fixing them. And the answer is yes, we looked at every single option. But we quickly decided against that because, as Randy Mills said:

“This is not a popularity contest, you can’t judge need by numbers, deciding the worth of something by how many people have it. We are disease agnostic. What we do is find the best science, and fund it.”

Another necessary element is developing better ways to attract greater investment from big pharmaceutical companies and venture capital to really help move the most promising projects through clinical trials and into patients. That is starting to happen, not as fast as we would like, but as our blog yesterday shows things are moving in this direction.

And the third piece of the pie is getting these treatments through the regulatory process, getting the Food and Drug Administration (FDA) to approve therapies for clinical trials. And this last piece clearly hit a nerve.

Many Patient Advocates expressed frustration at the slow pace of approval for any therapy by the FDA, some saying it felt like they just kept piling up obstacles in the way.

Dr. Mills said the FDA is caught between a rock and a hard place; criticized if it approves too slowly and chastised if it approves too fast, green lighting a therapy that later proves to have problems. But he agreed that changes are needed:

“The regulatory framework works well for things like drugs and small molecules that can be taken in pills but it doesn’t work well for cellular therapies like stem cells. It needs to do better at that.”

One Advocate suggested a Boot Camp for researchers, drilling them in the skills they’ll need to get FDA approval. Others suggested applying political pressure from Patient Advocacy groups to push for change.

As always there are no easy answers, but the meeting certainly raised many great questions. Those are all helping us focus our thinking on what needs to be in the Strategic Plan.

Randy ended the Patient Advocate events by saying the stem cell agency “is in the time business. What we do is time sensitive.” For too many people that time is already running out. We have to do everything we can to change that.

New Video: Paving a path to cures with the Alpha Stem Cell Clinics Network

In The Stem Cellar, you often read phrases like, “as their research progresses toward the clinic.” That’s because it’s a very noteworthy milestone to advance an initial idea in the laboratory to an actual experimental therapy that has approval to be tested in people. It’s a process that can be years in making. Through our support, several research teams in California have successfully delivered innovative stem cell-based therapies to clinical trials.

Now comes the hard part.

The scene shifts from a laboratory bench to hospital beds and clinic rooms with real life patients and a bustling medical staff. Considering many stem cell therapies are first-in-human studies and have no precedent, how do you get these clinical trials up and running?

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Enter CIRM’s Alpha Stem Cell Clinics Network, a $24 million initiative to provide the infrastructure necessary to get stem cell clinical trials off the ground in the most efficient manner possible. For example, efforts will include (but not limited to) teaching doctors and nurses new skills for administering stem cell therapies, helping to determine how the treatments will be paid for, sharing data between trial sites to improve outcomes, and educating patients about their treatment. We believe this investment will go a long way towards fulfilling the agency’s mission to accelerate the development of stem cell therapies to patients with unmet medical needs.

In late May, the three Network programs from UCSD, City of Hope, and the UCLA/UCI consortium joined CIRM at the City of Hope campus for a kickoff workshop to mark the beginning of the endeavor. We brought our cameras along and produced this short video about the Alpha Stem Cell Clinics Network, which features interviews with each trial center’s program director:

Share your voice, shape our future

shutterstock_201440705There is power in a single voice. I am always reminded of that whenever I meet a patient advocate and hear them talk about the need for treatments and cures – and not just for their particular disease but for everyone.

The passion and commitment they display in advocating for more research funding reflects the fact that everyday, they live with the consequences of the lack of effective therapies. So as we at CIRM, think about the stem cell agency’s future and are putting together a new Strategic Plan to help shape the direction we take, it only makes sense for us to turn to the patient advocate community for their thoughts and ideas on what that future should look like.

That’s why we are setting up three meetings in the next ten days in San Diego, Los Angeles and San Francisco to give our patient advocates a chance to let us know what they think, in person.

We have already sent our key stakeholders a survey to get their thoughts on the general direction for the Strategic Plan, but there is a big difference between ticking a box and having a conversation. These upcoming meetings are a chance to talk together, to explore ideas and really flesh out the details of what this Strategic Plan could be and should be.

Our President and CEO, Dr. C. Randal Mills wants each of those meetings to be an opportunity to hear, first hand, what people would like to see as we enter our second decade. We have close to one billion dollars left to invest in research so there’s a lot at stake and this is a great chance for patient advocates to help shape our next five years.

Every voice counts, so join us and make sure that yours is heard.

The events are:

San Diego, Monday, July 13th at noon at Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037

Los Angeles: Tuesday, July 14th at noon at Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, 1425 San Pablo Street, 1st floor conf. room Los Angeles, CA 90033

San Francisco: Wednesday, July 15th at noon at CIRM, 210 King Street (3rd floor), San Francisco, CA 94107

There will be parking at each event and a light lunch will be served.

We hope to see you at one of them and if you do plan on coming please RSVP to info@cirm.ca.gov

And of course please feel free to share this invitation to anyone you think might be interested in having their voice heard. We all have a stake in this.

Protein Revs Up Bone Stem Cells; Points Toward Future Osteoporosis Drug

Take a moment to feel your arm and wrist bones. They’re a lot more like solid rock than the soft stretchy skin that covers them. But bone is very much a living tissue continually being broken down and built back up in a process called bone remodeling. In people with osteoporosis, this balance tips toward bone breakdown leading to more porous, fragile bones with increased risk of fractures. An estimated ten million people in the U.S. have osteoporosis accounting for 1.5 million fractures annually at a cost of $17 billion in medical care, not to mention the emotional toll of these often debilitating and even life threatening injuries.

Fluorescent imaging mouse spines. Treatment with NELL-1 (right) shows greater bone formation compared to untreated mice (left). Credit: Broad Stem Cell Research Center

Fluorescent imaging of mouse spines. Treatment with NELL-1 (right) shows greater bone formation compared to untreated mice (left). Credit: Broad Stem Cell Research Center

This week a CIRM-funded research team at UCLA reported in Nature Communications that injection of a human protein called NELL-1 into the blood of mice with osteoporosis-like symptoms tipped the balance back toward bone formation. In a large animal study, delivering NELL-1 directly into the spine also led to increased bone volume. In a university press release, co-senior author Kang Ting spoke of his hopes that these results open up a new therapeutic avenue for treating osteoporosis and other ailments:

“Our end goal is really to harness the bone forming properties of NELL-1 to better treat patients with diverse causes of bone loss, from trauma in military personnel to osteoporosis from age, disease or very weak gravity, which causes bone loss in astronauts.”

In petri dish experiments leading up to these animal results, the research team showed that NELL-1 acts by increasing the specialization of mesenchymal stem cells – a type of adult stem cell found in the bone marrow and fat – into osteoblasts, the cells responsible for building new bone. At the same time, NELL-1 reduced the generation of osteoclasts, the cells responsible for the breakdown, or resorption, of bone. This dual action of NELL-1 explains how it improved the osteoporosis-like symptoms in the animals. Check out this fascinating animation for a visual description of osteoblasts and osteoclasts:

Many of the other molecules that promote bone growth aren’t as efficient as NELL-1: while they increase osteoblast numbers they also increase osteoclasts to some extent. For example, Fosamax is a drug prescribed to women with osteoporosis to help build stronger bones but long-term use has been associated with even more brittle bones and fractures. So this finding with NELL-1 sets it apart and hints at fewer side effects as a therapeutic. Still, it’s known to play a role in brain, cartilage, and blood vessel development so careful studies of non-bone effects are needed as the team pursues a road to the clinic.

For more information about CIRM-funded projects related to osteoporosis, visit our online fact sheet.

One man’s story points to hope against a deadly skin cancer

One of the great privileges and pleasures of working at the stem cell agency is the chance to meet and work with some remarkable people, such as my colleagues here at CIRM and the researchers we support. But for me the most humbling, and by far the most rewarding experience, is having a chance to get to know the people we work for, the patients and patient advocates.

Norm Beegun, got stem cell therapy for metastatic melanoma

Norm Beegun, got stem cell therapy for metastatic melanoma

At our May Board meeting I got to meet a gentleman who exemplifies everything that I truly admire about the patients and patient advocates. His name is Norm Beegun. And this is his story.

Norm lives in Los Angeles. In 2002 he went to see his regular doctor, an old high school friend, who suggested that since it had been almost ten years since he’d had a chest x-ray it might be a good idea to get one. At first Norm was reluctant. He felt fine, was having no health problems and didn’t see the need. But his friend persisted and so Norm agreed. It was a decision that changed, and ultimately saved, his life.

The x-ray showed a spot on his lung. More tests were done. They confirmed it was cancer; stage IV melanoma. They did a range of other examinations to see if they could spot any signs of the cancer on his skin, any potential warnings signs that they had missed. They found nothing.

Norm underwent surgery to remove the tumor. He also tried several other approaches to destroy the cancer. None of them worked; each time the cancer returned; each time to a different location.

Then a nurse who was working with him on these treatments suggested he see someone named Dr. Robert Dillman, who was working on a new approach to treating metastatic melanoma, one involving cancer stem cells.

Norm got in touch with Dr. Dillman and learned what the treatment involved; he was intrigued and signed up. They took some cells from Norm’s tumor and processed them, turning them into a vaccine, a kind of personalized therapy that would hopefully work with Norm’s own immune system to destroy the cancer.

That was in 2004. Once a month for the next six months he was given injections of the vaccine. Unlike the other therapies he had tried this one had no side effects, no discomfort, no pain or problems. All it did was get rid of the cancer. Regular scans since then have shown no sign that the melanoma has returned. Theoretically that could be because the new therapy destroyed the standard tumor cells as well as the cancer stem cells that lead to recurrence.

Norm says when you are diagnosed with an incurable life-threatening disease, one with a 5-year survival rate of only around 15%, you will try anything; so he said it wasn’t a hard decision to take part in the clinical trial, he felt he had nothing to lose.

“I didn’t know if it would help me. I didn’t think I’d be cured. But I wanted to be a guinea pig and perhaps help others.”

When he was diagnosed his son had just won a scholarship to play football at the University of California, Berkeley. Norm says he feared he would never be able to see his son play. But thanks to cleverly scheduling surgery during the off-season and having a stem cell therapy that worked he not only saw his son play, he never missed a game.

Norm returned to Berkeley on May 21st, 2015. He came to address the CIRM Board in support of an application by a company called NeoStem (which has just changed its name to Caladrius Biosciences). This was the company that had developed the cell therapy for metastatic melanoma that Norm took.

“Talking about this is still very emotional. When I got up to talk to the CIRM Board about this therapy, and ask them to support it, I wanted to let them know my story, the story of someone who had their life saved by this treatment. Because of this I am here today. Because of this I was able to see my son play. But just talking about it left me close to tears.”

It left many others in the room close to tears as well. The CIRM Board voted to fund the NeoStem application, investing $17.7 million to help the company carry out a Phase 3 clinical trial, the last hurdle it needs to clear to prove to the Food and Drug Administration that this should be approved for use in metastatic melanoma.

Norm says he is so grateful for the extra years he has had, and he is always willing to try and support others going through what he did:

“I counsel other people diagnosed with metastatic melanoma. I feel that I want to help others, to give them a sense of hope. It is such a wonderful feeling, being able to show other people that you can survive this disease.”

When you get to meet people like Norm, how could you not love this job.

A hopeful sight: therapy for vision loss cleared for clinical trial

Rosalinda Barrero

Rosalinda Barrero, has retinitis pigmentosa

Rosalinda Barrero says people often thought she was rude, or a snob, because of the way she behaved, pretending not to see them or ignoring them on the street. The truth is Rosalinda has retinitis pigmentosa (RP), a nasty disease, one that often attacks early in life and slowly destroys a person’s vision. Rosalinda’s eyes look normal but she can see almost nothing.

“I’ve lived my whole life with this. I told my daughters [as a child] I didn’t like to go Trick or Treating at Halloween because I couldn’t see. I’d trip; I’d loose my candy. I just wanted to stay home.”

Rosalinda says she desperately wants a treatment:

“Because I’m a mom and I would be so much a better mom if I could see. I could drive my daughters around. I want to do my part as a mom.”

Now a promising therapy for RP, funded by the stem cell agency, has been cleared by the Food and Drug Administration (FDA) to start a clinical trial in people.

The therapy was developed by Dr. Henry Klassen at the University of California, Irvine (UCI). RP is a relatively rare, inherited condition in which the light-sensitive cells at the back of the retina, cells that are essential for vision, slowly and progressively degenerate. Eventually it can result in blindness. There is no cure and no effective long-term treatment.

Dr. Klassen’s team will inject patients with stem cells, known as retinal progenitors, to help replace those cells destroyed by the disease and hopefully to save those not yet damaged.

In a news release about the therapy Dr. Klassen said the main goal of this small Phase I trial will be to make sure this approach is safe:

“This milestone is a very important one for our project. It signals a turning point, marking the beginning of the clinical phase of development, and we are all very excited about this project.”

Jonathan Thomas, the Chair of our Board, says that CIRM has invested almost $20 million to help support this work through early stage research and now, into the clinic.

“One of the goals of the agency is to provide the support that promising therapies need to progress and ultimately to get into clinical trials in patients. RP affects about 1.5 million people worldwide and is the leading cause of inherited blindness in the developed world. Having an effective treatment for it would transform people’s lives in extraordinary ways.”

Dr. Klassen says without that support it is doubtful that this work would have progressed as quickly as it has. And the support doesn’t just involve money:

“CIRM has played a critical and essential role in this project. While the funding is extremely important, CIRM also tutors and guides its grantees in the many aspects of translational development at every step of the way, and this accelerates during the later pre-clinical phase where much is at stake.”

This is now the 12th project that we are funding that has been approved by the FDA for clinical trials. It’s cause for optimism, but cautious optimism. These are small scale, early phase trials that in many cases are the first time these therapies have been tested in people. They look promising in the lab. Now it’s time to see if they are equally promising in people.

Considering we didn’t really start funding research until 2007 we have come a long way in a short time. Clearly we still have a long way to go. But the news that Dr. Klassen’s work has been given the go-ahead to take the next, big step, is a hopeful sign for Rosalinda and others with RP that we are at least heading in the right direction.

One of our recent Spotlight on Disease videos features Dr. Klassen and Rosalinda Barrero talking about RP.

This work will be one of the clinical trials being tested in our new Alpha Stem Cell Clinic Network. You can read more about that network here.

Brain’s Own Activity Can Fuel Growth of Deadly Brain Tumors, CIRM-Funded Study Finds

Not all brain tumors are created equal—some are far more deadly than others. Among the most deadly is a type of tumor called high-grade glioma or HGG. Most distressingly, HGG’s are the leading cause of brain tumor death in both children and adults. And despite extraordinary progress in cancer research as a whole, survival rates for those diagnosed with an HGG have yet to improve.

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But recent research from Stanford University scientists could one day help move the needle—and give renewed hope to the patients and their families affected by this devastating disease.

The study, published today in the journal Cell, found that one key driver for HGG’s deadly diagnosis is that the tumor can be stimulated to grow by the brain’s own neural activity—specifically the nerve activity in the brain’s cerebral cortex.

Michelle Monje, senior author of the study that was funded in part by two grants from CIRM, was initially surprised by these results, as they run counter to how most types of tumors grow. As she explained in today’s press release:

“We don’t think about bile production promoting liver cancer growth, or breathing promoting the growth of lung cancer. But we’ve shown that brain function is driving these brain cancers.”
 


By analyzing tumor cells extracted from HGG patients, and engrafting it onto mouse models in the lab, the researchers were able to pinpoint how the brain’s own activity was driving tumor growth.

The culprit: a protein called neuroligin-3 that appeared to be calling the shots. There are four distinct types of HGGs that affect the brain in vastly different ways—and have vastly different molecular and genetic characteristics. Interestingly, says Monje, neuroligin-3 played the same role in all of them.

What was so disturbing to the research team, says Monje, is that neuroligin-3 is an essential protein for overall brain development. Specifically, it helps maintain healthy growth and repair of brain tissue over time. In order to grow, HGG tumors hijack this critical protein.

The research team came to this conclusion after a series of experiments that delved deep into the molecular mechanisms that guide both brain activity and brain tumor development. They first employed a technique called optogenetics, whereby scientists use genetic manipulation to insert light-sensitive proteins into the brain cells, or neurons, of interest. This allowed scientists to activate these neurons—or deactivate them—at the ‘flick of a switch.’

When applying this technique to the tumor-engrafted mouse models, the team could then see that tumors grew significantly better when the neurons were switched on. The next step was to narrow it down to why. Additional biochemical analyses and testing on the mouse models confirmed that neuroligin-3 was being hijacked by the tumor to spur growth.

And when they dug deeper into the connection between neuroligin-3 and cancer, they found something even more disturbing. A detailed look at the Cancer Genome Atlas (a large public database of the genetics of human cancers), they found that HGG patients with higher levels of neuroligin-3 in their brain had shorter survival rates than those with lower levels of the same protein.

These results, while highlighting the particularly nefarious nature of this class of brain tumors, also presents enormous opportunity for researchers. Specifically, Monje hopes her team and others can find a way to block or nullify the presence of neuroligin-3 in the regions surrounding the tumor, creating a kind of barrier that can keep the size of the tumor in check. 


CIRM-Funded Scientists Build a Better Neuron; Gain New Insight into Motor Neuron Disease

Each individual muscle in our body—no matter how large or how small—is controlled by several types of motor neurons. Damage to one or more types of these neurons can give rise to some of the most devastating motor neuron diseases, many of which have no cure. But now, stem cell scientists at UCLA have manufactured a way to efficiently generate motor neuron subtypes from stem cells, thus providing an improved system with which to study these crucial cells.

“Motor neuron diseases are complex and have no cure; currently we can only provide limited treatments that help patients with some symptoms,” said senior author Bennett Novitch, in a news release. “The results from our study present an effective approach for generating specific motor neuron populations from embryonic stem cells to enhance our understanding of motor neuron development and disease.”

Normally, motor neurons work by transmitting signals between the brain and the body’s muscles. When that connection is severed, the individual loses the ability to control individual muscle movement. This is what happens in the case of amyotrophic lateral sclerosis, or ALS, also known as Lou Gehrig’s disease.

These images reveal the significance of the 'Foxp1 effect.' The Foxp1 transcription factor is crucial to the normal growth and function of motor neurons involved in limb-movement.

These images reveal the significance of the ‘Foxp1 effect.’ The Foxp1 transcription factor is crucial to the normal growth and function of motor neurons involved in limb-movement.

Recent efforts had focused on ways to use stem cell biology to grow motor neurons in the lab. However, such efforts to generate a specific type of motor neuron, called limb-innervating motor neurons, have not been successful. This motor-neuron subtype is particularly affected in ALS, as it supplies nerves to the arms and legs—the regions usually most affected by this deadly disease.

In this study, published this week in Nature Communications, Novitch and his team, including first author Katrina Adams, worked to develop a better method to produce limb-innervating motor neurons. Previous efforts had only had a success rate of about 3 percent. But Novitch and Adams were able to boost that number five-fold, to 20 percent.

Specifically, the UCLA team—using both mouse and human embryonic stem cells—used a technique called ‘transcriptional programming,’ in order to coax these stem cells into become fully functional, limb-innervating motor neurons.

In this approach, which was funded in part by a grant from CIRM, the team added a single transcription factor (a type of protein that regulates gene function), which would then guide the stem cell towards becoming the right type of motor neuron. Here, Novitch, Adams and the team used the Foxp1 transcription factor to do the job.

Normally, Foxp1 is found in healthy, functioning limb-innervating motor neurons. But in stem cell-derived motor neurons, Foxp1 was missing. So the team reasoned that Foxp1 might actually be the key factor to successfully growing these neurons.

Their initial tests of this theory, in which they inserted Foxp1 into a developing chicken spinal cord (a widely used model for neurological research), were far more successful. This result, which is not usually seen with most unmodified stem-cell-derived motor neurons, illustrates the important role played by Foxp1.

The most immediate implications of this research is that now scientists can now use this method to conduct more robust studies that enhance the understanding of how these cells work and, importantly, what happens when things go awry.

Building a Better Needle: CIRM-Funded Invention Gets Cells Into Brain More Safely, Efficiently

If NASA’s billion dollar Mars rovers deployed a bunch of dollar store party balloons to cushion the moment of impact, the mission would fail miserably. Likewise, the many years and millions of dollars spent on developing a stem cell-based therapy could be all for naught if the delivery of those precious cells into patients used cheap, inefficient tools.

That’s the subject of a recent TV interview with George Yu, who is CEO of Accurexa, a company that is developing and commercializing a novel syringe and needle device that could dramatically improve the delivery of cell therapies to the brain. The device was invented by UCSF neurosurgeon Daniel Lim with the support of a CIRM Tools and Technologies grant.

“So [Dr. Lim] participated in a phase 1 trial a few years ago where he was asked to deliver stem cell[-derived cells] to the brain and he didn’t really have adequate tools to do that, “ Yu explained in his interview with the New York-based finance and business TV program, New to the Street.

“The company that manufactured the stem cells spent millions of dollars in research but then they gave [Dr. Lim] a syringe and a needle that literally costs a couple of dollars. When he used that syringe and needle, which is a straight needle and injected those cells into the brain he actually saw a substantial amount of cells coming to the surface of the brain, which we call reflux, and that’s the reason he said there must be something better than this. And he applied for a grant, he got funded, and he invented the device. “

Not only does the standard straight syringe and needle cause a loss of transplanted cells due to reflux it also requires multiple injections in order to properly distribute the cell therapy in the brain. And with each injection, healthy brain tissue is damaged and increases the risk of stroke.

The Branched Point Device allows a well distributed cell transplantation into the brain with just one injection site. (image credit: Stereotact Funct Neurosurg. 2013; 91(2): 92–103.)

The Branched Point Device allows a well distributed transplantation of cells into the brain with just one injection site. (image credit: Stereotact Funct Neurosurg. 2013; 91(2): 92–103.)

Lim’s invention, called a Branched Point Device, avoids both cell reflux and the need for multiple injections. Instead of coming straight out of the needle tip, the cells are delivered through an opening that’s positioned on the side of the needle. So rather than re-injecting the needle, it’s incrementally rotated to deliver the cells in a different direction. With the use of a catheter that pokes through the needle, the cells can be distributed around the needle at different depths in a radial pattern much like the branches of a tree.

Use of the device in clinical trials may soon become a reality based on Yu’s comments in the interview:

“We’ve mostly completed our testing and the design of the device and we’re in the late stage of preparing a 510k submission to the FDA. So we expect that to happen this year. And once it’s FDA approved we can potentially sell the device.”

And because CIRM funded the development of this invention, the State of California is entitled to share in licensing revenue arising from the invention. Better still, the use of the device in clinical trials could provide more consistent, reliable results and a faster path to approval for stem cell-based therapies for neurodegenerative diseases like Parkinson’s.