Creating a diverse group of future scientists

Students in CIRM’s Bridges program showing posters of their work

If you have read the headlines lately, you’ll know that the COVID-19 pandemic is having a huge impact on the shipping industry. Container vessels are forced to sit out at anchor for a week or more because there just aren’t enough dock workers to unload the boats. It’s a simple rule of economics, you can have all the demand you want but if you don’t have the people to help deliver on the supply side, you are in trouble.

The same is true in regenerative medicine. The field is expanding rapidly and that’s creating a rising demand for skilled workers to help keep up. That doesn’t just mean scientists, but also technicians and other skilled individuals who can ensure that our ability to manufacture and deliver these new therapies is not slowed down.

That’s one of the reasons why CIRM has been a big supporter of training programs ever since we were created by the voters of California when they approved Proposition 71. And now we are kick-starting those programs again to ensure the field has all the talented workers it needs.

Last week the CIRM Board approved 18 programs, investing more than $86 million, as part of the Agency’s Research Training Grants program. The goal of the program is to create a diverse group of scientists with the knowledge and skill to lead effective stem cell research programs.

The awards provide up to $5 million per institution, for a maximum of 20 institutions, over five years, to support the training of predoctoral graduate students, postdoctoral trainees, and/or clinical trainees.

This is a revival of an earlier Research Training program that ran from 2006-2016 and trained 940 “CIRM Scholars” including:

• 321 PhD students
• 453 Postdocs
• 166 MDs

These grants went to academic institutions from UC Davis in Sacramento to UC San Diego down south and everywhere in-between. A 2013 survey of the students found that most went on to careers in the industry.

  • 56% continued to further training
  • 14% advanced to an academic research faculty position
  • 10.5% advanced to a biotech/industry position
  • 12% advanced to a non-research position such as teaching, medical practice, or foundation/government work

The Research Training Grants go to:

AWARDINSTITUTIONTITLEAMOUNT
EDUC4-12751Cedars-SinaiCIRM Training Program in Translational Regenerative Medicine    $4,999,333
EDUC4-12752UC RiversideTRANSCEND – Training Program to Advance Interdisciplinary Stem Cell Research, Education, and Workforce Diversity    $4,993,115
EDUC4-12753UC Los AngelesUCLA Training Program in Stem Cell Biology    $5 million
EDUC4-12756University of Southern CaliforniaTraining Program Bridging Stem Cell Research with Clinical Applications in Regenerative Medicine    $5 million
EDUC4-12759UC Santa CruzCIRM Training Program in Systems Biology of Stem Cells    $4,913,271
EDUC4-12766Gladstone Inst.CIRM Regenerative Medicine Research Training Program    $5 million
EDUC4-12772City of HopeResearch Training Program in Stem Cell Biology and Regenerative Medicine    $4,860,989
EDUC4-12782StanfordCIRM Scholar Training Program    $4,974,073
EDUC4-12790UC BerkeleyTraining the Next Generation of Biologists and Engineers for Regenerative Medicine    $4,954,238
EDUC4-12792UC DavisCIRM Cell and Gene Therapy Training Program 2.0    $4,966,300
EDUC4-12802Children’s Hospital of Los AngelesCIRM Training Program for Stem Cell and Regenerative Medicine Research    $4,999,500
EDUC4-12804UC San DiegoInterdisciplinary Stem Cell Training Grant at UCSD III    $4,992,446
EDUC4-12811ScrippsTraining Scholars in Regenerative Medicine and Stem Cell Research    $4,931,353
EDUC4-12812UC San FranciscoScholars Research Training Program in Regenerative Medicine, Gene Therapy, and Stem Cell Research    $5 million
EDUC4-12813Sanford BurnhamA Multidisciplinary Stem Cell Training Program at Sanford Burnham Prebys Institute, A Critical Component of the La Jolla Mesa Educational Network    $4,915,671  
EDUC4-12821UC Santa BarbaraCIRM Training Program in Stem Cell Biology and Engineering    $1,924,497
EDUC4-12822UC IrvineCIRM Scholars Comprehensive Research Training Program  $5 million
EDUC4-12837Lundquist Institute for Biomedical InnovationStem Cell Training Program at the Lundquist Institute    $4,999,999

These are not the only awards we make to support training the next generation of scientists. We also have our SPARK and Bridges to Stem Cell Research programs. The SPARK awards are for high school students, and the Bridges program for graduate or Master’s level students.

Celebrating a young life that almost wasn’t

Often on the Stem Cellar we feature CIRM-funded work that is helping advance the field, unlocking some of the secrets of stem cells and how best to use them to develop promising therapies. But every once in a while it’s good to remind ourselves that this work, while it may often seem slow, is already saving lives.

Meet Ja’Ceon Golden. He was one of the first patients treated at U.C. San Francisco, in partnership with St. Jude Children’s Hospital in Memphis, as part of a CIRM-funded study to treat a rare but fatal disorder called Severe Combined Immunodeficiency (SCID). Ja’Ceon was born without a functioning immune system, so even a simple cold could have been fatal.

At UCSF a team led by Dr. Mort Cowan, took blood stem cells from Ja’Ceon and sent them to St. Jude where another team corrected the genetic mutation that causes SCID. The cells were then returned to UCSF and re-infused into Ja’Ceon.  

Over the next few months those blood stem cells grew in number and eventually helped heal his immune system.

He recently came back to UCSF for more tests, just to make sure everything is OK. With him, as she has been since his birth, was his aunt and guardian Dannie Hawkins. She says Ja’Ceon is doing just fine, that he has just started pre-K, is about to turn five years old and in January will be five years post-therapy. Effectively, Ja’Ceon is cured.

SCID is a rare disease, there are only around 70 cases in the US every year, but CIRM funding has helped produce cures for around 60 kids so far. A recent study in the New England Journal of Medicine showed that a UCLA approach cured 95 percent of the children treated.

The numbers are impressive. But not nearly as impressive, or as persuasive of the power of regenerative medicine, as Ja’Ceon and Dannie’s smiles.

Ja’Ceon on his first day at pre-K. He loved it.

Gene therapy is life-changing for children with a life-threatening brain disorder

If you have never heard of AADC deficiency count yourself lucky. It’s a rare, incurable condition that affects only around 135 children worldwide but it’s impact on those children and their families is devastating. The children can’t speak, can’t feed themselves or hold up their head, they have severe mood swings and often suffer from insomnia.

But Dr. Krystof Bankiewicz, a doctor and researcher at the University of California San Francisco (UCSF), is using techniques he developed treating Parkinson’s disease to help those children. Full disclosure here, CIRM is funding Dr. Bankiewicz’s Parkinson’s clinical trial.

In AADC deficiency the children lack a critical enzyme that helps the brain make serotonin and dopamine, so called “chemical messengers” that help the cells in the brain communicate with each other. In his AADC clinical trial Dr. Bankiewicz and his team created a tiny opening in the skull and then inserted a functional copy of the AADC gene into two regions of the brain thought to have most benefit – the substantia nigra and ventral tegmental area of the brainstem.

Image showing target areas for AADC gene insertion: Courtesy UCSF

When the clinical trial began none of the seven children were able to sit up on their own, only two had any ability to control their head movement and just one could grasp an object in their hands. Six of the seven were described as moody or irritable and six suffered from insomnia.

In a news release Dr. Bankiewicz says the impact of the gene therapy was quite impressive: “Remarkably, these episodes were the first to disappear and they never returned. In the months that followed, many patients experienced life-changing improvements. Not only did they begin laughing and have improved mood, but some were able to start speaking and even walking.”

Those weren’t the only improvements, at the end of one year:

  • All seven children had better control of their head and body.
  • Four of the children were able to sit up by themselves.
  • Three patients could grasp and hold objects.
  • Two were able to walk with some support.

Two and a half years after the surgery:

  • One child was able to walk without any support.
  • One child could speak with a vocabulary of 50 words.
  • One child could communicate using an assistive device.

The parents also reported big improvements in mood and ability to sleep.

UCSF posted some videos of the children before and after the surgery and you can see for yourself the big difference in the children. It’s not a cure, but for families that had nothing in the past, it is a true gift.

The study is published in the journal Nature Communications.

CIRM Builds Out World Class Team With 5 New hires

Kevin Marks, CIRM’s new General Counsel. Photo courtesy Modern-Counsel.com

Following the passage of Proposition 14 CIRM has hired five new employees to help increase the team’s ability to respond to new challenges and responsibilities.

Prop 14, which was approved by voters in November 2020, gives CIRM $5.5 billion in new funding. Those funds mean CIRM can once again fund research from Discovery, through Translational and Clinical, as well as create new education and training programs. Prop 14 also adds new areas of focus for the Stem Cell Agency including creating an Accessibility and Affordability Working Group, expanding the Alpha Stem Cell Clinic network and creating new Centers of Excellence in underserved parts of California. To meet those new responsibilities the Agency has hired a highly talented group of individuals. Those include:

Kevin Marks is CIRM’s new General Counsel. Kevin studied Russian at college and originally wanted to be a diplomat, but when that didn’t work out he turned to the law. He became a highly accomplished, skilled advisor with global and domestic expertise and a history of delivering innovative legal and business results. He has served as Vice President and Head of Legal and Compliance at Roche Molecular Solutions, VP and General Counsel at Roche Molecular Diagnostics and VP and General Counsel at Roche Palo Alto, LLC.

“We are so delighted to have Kevin Marks join CIRM as a member of our executive Leadership Team,” says Maria T. Millan, MD, CIRM’s President and CEO. “He brings unique qualifications and critical skills during the formative phase and launch of our new strategic plan for California’s $5.5B investment in stem cell, genomics and regenerative medicine research and therapy development. As general counsel, he will oversee the legal department, human resources, grants management and operations at the Agency. Kevin has an established track record with global and domestic expertise and a history of delivering innovative legal and business solutions.”

“He is revered by his colleagues as an exceptional leader in his profession and in the community. Kevin is known for developing people as well as programs, and for promoting racial, ethnic and gender diversity.”

“I am incredibly honored to be joining CIRM at this stage of its journey,” says Marks. “I see the opportunity to contribute to positive patient outcomes–especially those patients with unmet medical needs–by working towards accelerating stem cell research in California as a member of the CIRM team as rewarding and perfectly aligned with my professional and personal goals.”

Pouneh Simpson as Director of Finance. Pouneh comes to CIRM from the Governor’s Office of Emergency Services in California, where she served as the Recovery Financial Administration Chief. At OES she worked with local, state, and federal government stakeholders on disaster recovery planning, exercises, and grant administration, specifically, overseeing the grant processing of all disaster recovery activity.

Prior to that Pouneh worked as the Chief Financial Officer of the Veterans Homes, where she managed finances at eight Veterans Homes with over 2,800 positions and $365 million in General Fund support. She also led the writing of legislation, regulations, policies and procedures for Cal Vet, overhauling the business and financial portions of eight Veterans Homes.

Mitra Hooshmand, PhD. as Senior Science Officer for Special Projects and Initiatives. Mitra joins CIRM after more than five years of leadership experience at Americans for Cures, a stem cell advocacy group. During this time, she mobilized hundreds of stakeholders, from scientists to national and local patient advocacy organizations, to generate support for CIRM’s mission.

Mitra has a PhD. in Anatomy and Biology from the University of California at Irvine. She also worked as a Project Scientist at the Sue and Bill Gross Stem Cell Research Center at UC Irvine, where she conducted and published academic and industry-partnered research in studies investigating the therapeutic benefit of human neural stem cell transplantation in preclinical models of spinal cord injury and aging.

Vanessa Singh, as Human Resources Manager. Vanessa has 15 years of experience working for the state of California, working at the Departments of General Services, Insurance and Human Services. In those roles she gained experience in performing, processing, developing, implementing, and advising on many personnel aspects such as compensation, benefits, classifying positions, recruitment and hiring, salary structure (exempt and civil service), organization structure, and retirement.

When COVID struck Vanessa stepped up to help. She worked as a Case Investigator for San Bernardino Local Health Jurisdiction, Department of Public Health, doing contact tracing. She talked to people diagnosed with coronavirus and collected information on people they may have had close contact with who may have been exposed to the virus.

Claudette Mandac as Project Manager Review. Claudette has more than seven years’ experience with UCSF’s Human Research Protection Program. In that role she prepared protocols for scientific, regulatory and ethical review, pre-screening submissions to ensure they were complete and consistent, and then routing them to the appropriate reviewers for administrative, expedited or Committee review. She also managed an Institutional Review Board Committee, preparing and distributing protocols for review by designated scientific and nonscientific reviewers, coordinating meetings, recruiting and training members, and maintaining records of conflicts of interest. At UCSF she annually helped process up to 3,000 IRB modifications, continuing reviews, and post-approval safety reports for domestic and international socio-behavioral or biomedical research.

Claudette has two degrees from U.C. Berkeley; one in Arts and History and another in Science, Conservation and Resource Studies.

It’s all about the patients

Ronnie, born with a fatal immune disorder now leading a normal life thanks to a CIRM-funded stem cell/gene therapy: Photo courtesy of his mum Upasana

Whenever you are designing something new you always have to keep in mind who the end user is. You can make something that works perfectly fine for you, but if it doesn’t work for the end user, the people who are going to work with it day in and day out, you have been wasting your time. And their time too.

At CIRM our end users are the patients. Everything we do is about them. Starting with our mission statement: to accelerate stem cell treatments to patients with unmet medical needs. Everything we do, every decision we make, has to keep the needs of the patient in mind.

So, when we were planning our recent 2020 Grantee Meeting (with our great friends and co-hosts UC Irvine and UC San Diego) one of the things we wanted to make sure didn’t get lost in the mix was the face and the voice of the patients. Often big conferences like this are heavy on science with presentations from some of the leading researchers in the field. And we obviously wanted to make sure we had that element at the Grantee meeting. But we also wanted to make sure that the patient experience was front and center.

And we did just that. But more on that in a minute. First, let’s talk about why the voice of the patient is important.

Some years ago, Dr. David Higgins, a CIRM Board member and patient advocate for Parkinson’s Disease (PD), said that when researchers are talking about finding treatments for PD they often focus on the dyskinesia, the trembling and shaking and muscle problems. However, he said if you actually asked people with PD you’d find they were more concerned with other aspects of the disease, the insomnia, anxiety and depression among other things. The key is you have to ask.

Frances Saldana, a patient advocate for research into Huntington’s disease

So, we asked some of our patient advocates if they would be willing to be part of the Grantee Meeting. All of them, without hesitation, said yes. They included Frances Saldana, a mother who lost three of her children to Huntington’s disease; Kristin MacDonald, who lost her sight to a rare disorder but regained some vision thanks to a stem cell therapy and is hoping the same therapy will help restore some more; Pawash Priyank, whose son Ronnie was born with a fatal immune disorder but who, thanks to a stem cell/gene therapy treatment, is now healthy and leading a normal life.

Because of the pandemic everything was virtual, but it was no less compelling for that. We interviewed each of the patients or patient advocates beforehand and those videos kicked off each session. Hearing, and seeing, the patients and patient advocates tell their stories set the scene for what followed. It meant that the research the scientists talked about took on added significance. We now had faces and names to highlight the importance of the work the scientists were doing. We had human stories. And that gave a sense of urgency to the work the researchers were doing.

But that wasn’t all. After all the video presentations each session ended with a “live” panel discussion. And again, the patients and patient advocates were a key part of that. Because when scientists talk about taking their work into a clinical trial they need to know if the way they are setting up the trial is going to work for the patients they’re hoping to recruit. You can have the best scientists, the most promising therapy, but if you don’t design a clinical trial in a way that makes it easy for patients to be part of it you won’t be able to recruit or retain the people you need to test the therapy.

Patient voices count. Patient stories count.

But more than anything, hearing and seeing the people we are trying to help reminds us why we do this work. It’s so easy to get caught up in the day to day business of our jobs, struggling to get an experiment to work, racing to get a grant application in before the deadline. Sometimes we get so caught up in the minutiae of work we lose sight of why we are doing it. Or who we are doing it for.

At CIRM we have a saying; come to work every day as if lives depend on you, because lives depend on you. Listening to the voices of patients, seeing their faces, hearing their stories, reminds us not to waste a moment. Because lives depend on all of us.

Here’s one of the interviews that was featured at the event. I do apologize in advance for the interviewer, he’s rubbish at his job.

CIRM Board Approves Clinical Trials Targeting COVID-19 and Sickle Cell Disease

Coronavirus particles, illustration.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved new clinical trials for COVID-19 and sickle cell disease (SCD) and two earlier stage projects to develop therapies for COVID-19.

Dr. Michael Mathay, of the University of California at San Francisco, was awarded $750,000 for a clinical trial testing the use of Mesenchymal Stromal Cells for respiratory failure from Acute Respiratory Distress Syndrome (ARDS). In ARDS, patients’ lungs fill up with fluid and are unable to supply their body with adequate amounts of oxygen. It is a life-threatening condition and a major cause of acute respiratory failure. This will be a double-blind, randomized, placebo-controlled trial with an emphasis on treating patients from under-served communities.

This award will allow Dr. Matthay to expand his current Phase 2 trial to additional underserved communities through the UC Davis site.

“Dr. Matthay indicated in his public comments that 12 patients with COVID-related ARDS have already been enrolled in San Francisco and this funding will allow him to enroll more patients suffering from COVID- associated severe lung injury,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM, in addition to the NIH and the Department of Defense, has supported Dr. Matthay’s work in ARDS and this additional funding will allow him to enroll more COVID-19 patients into this Phase 2 blinded randomized controlled trial and expand the trial to 120 patients.”

The Board also approved two early stage research projects targeting COVID-19.

  • Dr. Stuart Lipton at Scripps Research Institute was awarded $150,000 to develop a drug that is both anti-viral and protects the brain against coronavirus-related damage.
  • Justin Ichida at the University of Southern California was also awarded $150,00 to determine if a drug called a kinase inhibitor can protect stem cells in the lungs, which are selectively infected and killed by the novel coronavirus.

“COVID-19 attacks so many parts of the body, including the lungs and the brain, that it is important for us to develop approaches that help protect and repair these vital organs,” says Dr. Millan. “These teams are extremely experienced and highly renowned, and we are hopeful the work they do will provide answers that will help patients battling the virus.”

The Board also awarded Dr. Pierre Caudrelier from ExcellThera $2 million to conduct a clinical trial to treat sickle cell disease patients

SCD is an inherited blood disorder caused by a single gene mutation that results in the production of “sickle” shaped red blood cells. It affects an estimated 100,000 people, mostly African American, in the US and can lead to multiple organ damage as well as reduced quality of life and life expectancy.  Although blood stem cell transplantation can cure SCD fewer than 20% of patients have access to this option due to issues with donor matching and availability.

Dr. Caudrelier is using umbilical cord stem cells from healthy donors, which could help solve the issue of matching and availability. In order to generate enough blood stem cells for transplantation, Dr. Caudrelier will be using a small molecule to expand these blood stem cells. These cells would then be transplanted into twelve children and young adults with SCD and the treatment would be monitored for safety and to see if it is helping the patients.

“CIRM is committed to finding a cure for sickle cell disease, the most common inherited blood disorder in the U.S. that results in unpredictable pain crisis, end organ damage, shortened life expectancy and financial hardship for our often-underserved black community” says Dr. Millan. “That’s why we have committed tens of millions of dollars to fund scientifically sound, innovative approaches to treat sickle cell disease. We are pleased to be able to support this cell therapy program in addition to the gene therapy approaches we are supporting in partnership with the National Heart, Lung and Blood Institute of the NIH.”

How developing a treatment for a rare disease could lead to therapies for other, not-so-rare conditions

Logan Lacy, a child with AADC Deficiency: Photo courtesy Chambersburg Public Opinion

Tomorrow, the last day in February, is Rare Disease Day. It’s a day dedicated to raising awareness about rare diseases and the impact they have on patients and their families.

But the truth is rare diseases are not so rare. There are around 7,000 diseases that affect fewer than 200,000 Americans at any given time. In fact, it’s estimated that around one in 20 people will live with a rare disease at some point in their lives. Many may die from it.

This blog is about one man’s work to find a cure for one of those rare diseases, and how that could lead to a therapy for something that affects many millions of people around the world.

Dr. Krystof Bankiewicz; Photo courtesy Ohio State Medical Center

Dr. Krystof Bankiewicz is a brain surgeon at U.C. San Francisco and The Ohio State University. He is also the President and CEO at Brain Neurotherapy Bio and a world expert in delivering gene and other therapies to the brain. More than 20 years ago, he began trying to develop a treatment for Parkinson’s disease by looking at a gene responsible for AADC enzyme production, which plays an important role in the brain and central nervous system.  AADC is critical for the formation of serotonin and dopamine, chemicals that transmit signals between nerve cells, the latter of which plays a role in the development of Parkinson’s disease.

While studying the AADC enzyme, Dr. Bankiewicz learned of an extremely rare disorder where children lack the AADC enzyme that is critical for their development.  This condition significantly inhibits communication between the brain and the rest of the body, leading to extremely limited mobility, muscle spasms, and problems with overall bodily functions.  As a result of this, AADC deficient children require lifelong care, and particularly severe cases can lead to death in the first ten years of life.

“These children can’t speak. They have no muscle control, so they can’t do fundamental things such as walking, supporting their neck or lifting their arms,” says Dr. Bankiewicz. “They have involuntary movements, experience tremendously painful spasms almost like epileptic seizures. They can’t feed themselves and have to be fed through a tube in their stomach.”

So, Dr. Bankiewicz, building on his understanding of the gene that encodes AADC, developed an experimental approach to deliver a normal copy, injected directly into the midbrain, the area responsible for dopamine production. The DDC gene was inserted into a virus that acted as a kind of transport, carrying the gene into neurons, the brain cells affected by the condition. It was hoped that once inside, the gene would allow the body to produce the AADC enzyme and, in turn, enable it to produce its own dopamine .

And that’s exactly what happened.

“It’s unbelievable. In the first treated patients their motor system is dramatically improved, they are able to better control their movements, they can eat, they can sleep well. These are tremendous benefits. We have been following these children for almost three years post-treatment, and the progression we see doesn’t stop, it keeps going and we see these children keep on improving. Now they are able to get physical therapy to help them. Some are even able to go to school.”

For Dr. Bankiewicz this has been decades in the making, but that only makes it all the more gratifying: “This doesn’t happen very often in your lifetime, to be able to use all your professional experience and education to help people and see the impact it has on people’s lives.”

So far he has treated 20 patients from the US, UK and all over the world.

But he is far from finished.

Already the therapy has been given Orphan Drug Designation and Regenerative Medicine Advanced Therapy designation by the US Food and Drug Administration. The former is a kind of financial incentive to companies to develop drugs for rare diseases. The latter gives therapies that are proving to be both safe and effective, an accelerated path to approval for wider use. Dr. Bankiewicz hopes that will help them raise the funds needed to treat children with this rare condition.  “We want to make this affordable for families. We are not in this to make a profit; we want to get foundations and maybe even pharmaceutical companies to help us treat the kids, so they don’t have to cover the full costs themselves.”

CIRM has not funded any of this work, but the data and results from this research were important factors in our Board awarding Dr. Bankiewicz more than $5.5 million to begin a clinical trial for Parkinson’s disease. Dr. Bankiewicz is using a similar approach in that work to the one he has shown can help children with AADC deficiency.

While AADC deficiency may only affect a few hundred children worldwide, it’s estimated that Parkinson’s affects more than ten million people; one million of those in the US alone.  Developing this gene therapy technique in a rare disease, therefore, may ultimately benefit large populations of patients.

So, on this Rare Disease Day, we celebrate Dr. Bankiewicz and others whose compassion and commitment to finding treatments to help those battling rare conditions are helping change the world, one patient at a time.

You can follow the story of one child treated by Dr. Bankiewicz here.

The Top CIRM Blogs of 2019

This year the most widely read blog was actually one we wrote back in 2018. It’s the transcript of a Facebook Live: “Ask the Stem Cell Team” event about strokes and stroke recovery. Because stroke is the third leading cause of death and disability in the US it’s probably no surprise this blog has lasting power. So many people are hoping that stem cells will help them recover from a stroke.

But of the blogs that we wrote and posted this year there’s a really interesting mix of topics.

The most read 2019 blog was about a potential breakthrough in the search for a treatment for type 1 diabetes (T1D).  Two researchers at UC San Francisco, Dr. Matthias Hebrok and Dr. Gopika Nair developed a new method of replacing the insulin-producing cells in the pancreas that are destroyed by type 1 diabetes. 

Dr. Matthias Hebrok
Dr. Gopika Nair

Dr. Hebrok described it as a big advance saying: “We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.”

It’s not too surprising a blog about type 1 diabetes was at the top. This condition affects around 1.25 million Americans, a huge audience for any potential breakthrough. However, the blog that was the second most read is the exact opposite. It is about a rare disease called cystinosis. How rare? Well, there are only around 500 children and young adults in the US, and just 2,000 worldwide diagnosed with this condition.  

It might be rare but its impact is devastating. A genetic mutation means children with this condition lack the ability to clear an amino acid – cysteine – from their body. The buildup of cysteine leads to damage to the kidneys, eyes, liver, muscles, pancreas and brain.

Dr. Stephanie Cherqui

UC San Diego researcher Dr. Stephanie Cherqui and her team are taking the patient’s own blood stem cells and, in the lab, genetically re-engineering them to correct the mutation, then returning the cells to the patient. It’s hoped this will create a new, healthy blood system free of the disease.

Dr. Cherqui says if it works, this could help not just people with cystinosis but a wide array of other disorders: “We were thrilled that the stem cells and gene therapy worked so well to prevent tissue degeneration in the mouse model of cystinosis. This discovery opened new perspectives in regenerative medicine and in the application to other genetic disorders. Our findings may deliver a completely new paradigm for the treatment of a wide assortment of diseases including kidney and other genetic disorders.”

Sickled cells

The third most read blog was about another rare disease, but one that has been getting a lot of media attention this past year. Sickle cell disease affects around 100,000 Americans, mostly African Americans. In November the Food and Drug Administration (FDA) approved Oxbryta, a new therapy that reduces the likelihood of blood cells becoming sickle shaped and clumping together – causing blockages in blood vessels.

But our blog focused on a stem cell approach that aims to cure the disease altogether. In many ways the researchers in this story are using a very similar approach to the one Dr. Cherqui is using for cystinosis. Genetically correcting the mutation that causes the problem, creating a new, healthy blood system free of the sickle shaped blood cells.

Two other blogs deserve honorable mentions here as well. The first is the story of James O’Brien who lost the sight in his right eye when he was 18 years old and now, 25 years later, has had it restored thanks to stem cells.

The fifth most popular blog of the year was another one about type 1 diabetes. This piece focused on the news that the CIRM Board had awarded more than $11 million to Dr. Peter Stock at UC San Francisco for a clinical trial for T1D. His approach is transplanting donor pancreatic islets and parathyroid glands into patients, hoping this will restore the person’s ability to create their own insulin and control the disease.

2019 was certainly a busy year for CIRM. We are hoping that 2020 will prove equally busy and give us many new advances to write about. You will find them all here, on The Stem Cellar.

A future scientist’s journey

All this week we have been highlighting blogs from our SPARK (Summer Program to Accelerate Regenerative medicine Knowledge) students. SPARK gives high school students a chance to spend their summer working in a world class stem cell research facility here in California. In return they write about their experiences and what they learned.

The standard for blogs this year was higher than ever, so choosing a winner was particularly tough. In the end we chose Abigail Mora, who interned at UC San Francisco. We felt the obstacles she overcame in getting to this point made her story all the more remarkable and engaging.

Abigail Mora

When I was 15, my mother got sick and went to several doctors. Eventually, she found out that she was pregnant with a 3-month-old baby. A month after, my mom fell from the stairs, which were not high but still dangerous. Luckily, everything seemed to be okay with the baby. In the last week of her six-month pregnancy, she went in the clinic for a regular check-up but she ended up giving birth to my brother, who was born prematurely. She stayed in the clinic for a month and my brother also had to stay so that his lungs could develop properly.

When he came home, I was so happy. I spent a lot of time with him and was like his second mom. After an initial period of hard time, he grew into a healthy kid. Then I moved to San Francisco with my aunt, leaving my parents and siblings in Mexico so that I could become a better English speaker and learn more about science. My experience with my brother motivated me to learn more about the condition of premature babies, since there are many premature babies who are not as fortunate. I want to study neurodevelopment in premature kids, and how it may go wrong.

I was so happy when I got into the SEP High School Program, which my chemistry teacher introduced me to, and I found the research of Eric Huang’s lab at UCSF about premature babies and stem cell development in the brain super interesting. I met Lakisha and Jean, and they introduced me to the lab and helped me walk through the training process.

My internship experience was outstanding: I enjoyed doing research and how my mentor Jiapei helped me learn new things about the brain. I learned that there are many different cell types in the brain, like microglia, progenitor cells, and intermediate progenitors.

As all things in life can be challenging, I was able to persevere with my mentor’s help. For example, when I first learned how to cut mouse brains using a cryostat, I found it hard to pick up the tissue onto slides. After practicing many times, I became more familiar with the technique and my slices got better. Another time, I was doing immunostaining and all the slices fell from the slide because we didn’t bake the slides long enough. I was sad, but we learned from our mistakes and there are a lot of trials and errors in science.

I’ve also learned that in science, since we are studying the unknown, there is not a right or wrong answer. We use our best judgement to draw conclusions from what we observe, and we repeat the experiment if it’s not working.

The most challenging part of this internship was learning and understanding all the new words in neuroscience. Sometimes, I got confused with the abbreviations of these words. I hope in the future I can explain as well as my mentor Jiapei explained to me.

My parents are away from me but they support me, and they think that this internship will open doors to better opportunities and help me grow as a person.

I want to become a researcher because I want to help lowering the risk of neurodevelopmental disorders in premature babies. Many of these disorders, such as autism or schizophrenia, don’t have cures. These are some of the hardest diseases to cure because people aren’t informed about them and not enough research has been done. Hopefully, one day I can work on developing a cure for these disorders.

CIRM’s Stephen Lin, PhD, who heads the SPARK program and Abigail after her blog won first prize

Stories that caught our eye: SanBio’s Traumatic Brain Injury trial hits its target; A new approach to endometriosis; and a SCID kid celebrates Halloween in style

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Traumatic brain injury: graphic courtesy Brainline.org

Hopeful signs for treating brain injuries

There are more than 200,000 cases of traumatic brain injury (TBI) in the US every year. The injuries can be devastating, resulting in everything from difficult sleeping to memory loss, depression and severe disability. There is no cure. But this week the SanBio Group had some encouraging news from its Phase 2 STEMTRA clinical trial.

In the trial patients with TBI were given stem cells, derived from the bone marrow of healthy adult donors. When transplanted into the area of injury in the brain, these cells appear to promote recovery by stimulating the brain’s own regenerative ability.

In this trial the cells demonstrated what the company describes as “a statistically significant improvement in their motor function compared to the control group.”

CIRM did not fund this research but we are partnering with SanBio on another clinical trial targeting stroke.

 

Using a woman’s own cells to heal endometriosis

Endometriosis is an often painful condition that is caused when the cells that normally line the inside of the uterus grow outside of it, causing scarring and damaging other tissues. Over time it can result in severe pain, infertility and increase a woman’s risk for ovarian cancer.

There is no effective long-term treatment but now researchers at Northwestern Medicine have developed an approach, using the woman’s own cells, that could help treat the problem.

The researchers took cells from women, turned them into iPS pluripotent stem cells and then converted those into healthy uterine cells. In laboratory tests these cells responded to the progesterone, the hormone that plays a critical role in the uterus.

In a news release, Dr. Serdar Bulun, a senior author of the study, says this opens the way to testing these cells in women:

“This is huge. We’ve opened the door to treating endometriosis. These women with endometriosis start suffering from the disease at a very early age, so we end up seeing young high school girls getting addicted to opioids, which totally destroys their academic potential and social lives.”

The study is published in the journal Stem Cell Reports.

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Happy Halloween from a scary SCID kid

A lot of the research we write about on the Stem Cellar focuses on potential treatments or new approaches that show promise. So every once in a while, it’s good to remind ourselves that there are already stem cell treatments that are not just showing promise, they are saving lives.

That is the case with Ja’Ceon Golden. Regular readers of our blog know that Ja’Ceon was diagnosed with Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease” when he was just a few months old. Children born with SCID often die in the first few years of life because they don’t have a functioning immune system and so even a simple infection can prove life-threatening.

Fortunately Ja’Ceon was enrolled in a CIRM-funded clinical trial at UC San Francisco where his own blood stem cells were genetically modified to correct the problem.

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Today he is a healthy, happy, thriving young boy. These pictures, taken by his great aunt Dannie Hawkins, including one of him in his Halloween costume, show how quickly he is growing. And all thanks to some amazing researchers, an aunt who wouldn’t give up on him, and the support of CIRM.