Antibody effective in cure for rare blood disorders

3D illustration of an antibody binding to a designated target.
Illustration created by Audra Geras.

A variety of diseases can be traced to a simple root cause: problems in the bone marrow. The bone marrow contains specialized stem cells known as hematopoietic stem cells (HSCs) that give rise to different types of blood cells. As mentioned in a previous blog about Sickle Cell Disease (SCD), one problem that can occur is the production of “sickle like” red blood cells. In blood cancers like leukemia, there is an uncontrollable production of abnormal white blood cells. Another condition, known as myelodysplastic syndromes (MDS), are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells.

For diseases that originate in the bone marrow, one treatment involves introducing healthy HSCs from a donor or gene therapy. However, before this type of treatment can take place, all of the problematic HSCs must be eliminated from the patient’s body. This process, known as pre-treatment, involves a combination of chemotherapy and radiation, which can be extremely toxic and life threatening. There are some patients whose condition has progressed to the point where their bodies are not strong enough to withstand pre-treatment. Additionally, there are long-term side effects that chemotherapy and radiation can have on infant children that are discussed in a previous blog about pediatric brain cancer.

Could there be a targeted, non-toxic approach to eliminating unwanted HSCs that can be used in combination with stem cell therapies? Researchers at Stanford say yes and have very promising results to back up their claim.

Dr. Judith Shizuru and her team at Stanford University have developed an antibody that can eliminate problematic blood forming stem cells safely and efficiently. The antibody is able to identify a protein on HSCs and bind to it. Once it is bound, the protein is unable to function, effectively removing the problematic blood forming stem cells.

Dr. Shizuru is the senior author of a study published online on February 11th, 2019 in Blood that was conducted in mice and focused on MDS. The results were very promising, demonstrating that the antibody successfully depleted human MDS cells and aided transplantation of normal human HSCs in the MDS mouse model.

This proof of concept holds promise for MDS as well as other disease conditions. In a public release from Stanford Medicine, Dr. Shizuru is quoted as saying, “A treatment that specifically targets only blood-forming stem cells would allow us to potentially cure people with diseases as varied as sickle cell disease, thalassemia, autoimmune disorders and other blood disorders…We are very hopeful that this body of research is going to have a positive impact on patients by allowing better depletion of diseased cells and engraftment of healthy cells.”

The research mentioned was partially funded by us at CIRM. Additionally, we recently awarded a $3.7 million dollar grant to use the same antibody in a human clinical trial for the so-called “bubble baby disease”, which is also known as severe combined immunodeficiency (SCID). You can read more about that award on a previous blog post linked here.

Tips on how to be a great Patient Advocate from three of the best Advocates around

No one sets out to be a Patient Advocate. It’s something that you become because of something that happens to you. Usually it’s because you, or  a loved one or a friend, becomes ill and you want to help find a treatment. Whatever the reason, it is the start of a journey that often throws you into a world that you know nothing about: a world of research studies and scientific terminology, of talking to and trying to understand medical professionals, and of watching someone you love struggle.

It’s a tough, demanding, sometimes heart-breaking role. But it’s also one of the most important roles you can ever take on. Patient Advocates not only care for people afflicted with a particular disease or disorder, they help them navigate a new and scary world, they help raise money for research, and push researchers to work harder to find new treatments, maybe even cures. And they remind all of us that in the midst of pain and suffering the human touch, a simple kindness is the most important gift of all.

But what makes a great Patient Advocate, what skills do you need and how can you get them? At CIRM we are blessed to have some of the most amazing Patient Advocates you will ever meet. So we asked three of them to join us for a special Facebook Live “Ask the Stem Cell Team” event to share their knowledge, experience and expertise with you.

The Facebook Live “Ask the Stem Cell Team About Patient Advocacy” event will be on Thursday, March 14th from noon till 1pm PST.

The three experts are:

Gigi McMillan

Gigi McMillan became a Patient Advocate when her 5-year-old son was diagnosed with a brain tumor. That has led her to helping develop support systems for families going through the same ordeal, to help researchers develop appropriate consent processes and to campaign for the rights of children and their families in research.

Adrienne Shapiro

Adrienne Shapiro comes from a family with a long history of Sickle Cell Disease (SCD) and has fought to help people with SCD have access to compassionate care. She is the co-founder of Axis Advocacy, an organization dedicated to raising awareness about SCD and support for those with it. In addition she is now on the FDA’s Patient Engagement Collaborative, a new group helping the FDA ensure the voice of the patient is heard at the highest levels.

David Higgins

David Higgins is a CIRM Board member and a Patient Advocate for Parkinson’s Disease. David has a family history of the disease and in 2011 was diagnosed with Parkinson’s. As a scientist and advocate he has championed research into the disease and strived to raise greater awareness about the needs of people with Parkinson’s.

Please join us for our Facebook Live event on Patient Advocates on Thursday, March 14 from noon till 1pm and feel free to share information about the event with anyone you think would be interested.

Also, make sure to “like” our FaceBook page before the event to receive a notification when we’ve gone live for this and future events. If you miss the broadcast, not to worry. We’ll be posting it on our Facebook video page, our website, and YouTube channel shortly afterwards.

We want to answer your most pressing questions, so please email them directly to us beforehand at info@cirm.ca.gov.

Rare Disease Gets Big Boost from California’s Stem Cell Agency

UC Irvine’s Dr. Leslie Thompson and patient advocate Frances Saldana after the CIRM Board vote to approve funding for Huntington’s disease

If you were looking for a poster child for an unmet medical need Huntington’s disease (HD) would be high on the list. It’s a devastating disease that attacks the brain, steadily destroying the ability to control body movement and speech. It impairs thinking and often leads to dementia. It’s always fatal and there are no treatments that can stop or reverse the course of the disease. Today the Board of the California Institute for Regenerative Medicine (CIRM) voted to support a project that shows promise in changing that.

The Board voted to approve $6 million to enable Dr. Leslie Thompson and her team at the University of California, Irvine to do the late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. The therapy involves transplanting stem cells that have been turned into neural stem cells which secrete a molecule called brain-derived neurotrophic factor (BDNF), which has been shown to promote the growth and improve the function of brain cells. The goal is to slow down the progression of this debilitating disease.

“Huntington’s disease affects around 30,000 people in the US and children born to parents with HD have a 50/50 chance of getting the disease themselves,” says Dr. Maria T. Millan, the President and CEO of CIRM. “We have supported Dr. Thompson’s work for a number of years, reflecting our commitment to helping the best science advance, and are hopeful today’s vote will take it a crucial step closer to a clinical trial.”

Another project supported by CIRM at an earlier stage of research was also given funding for a clinical trial.

The Board approved almost $12 million to support a clinical trial to help people undergoing a kidney transplant. Right now, there are around 100,000 people in the US waiting to get a kidney transplant. Even those fortunate enough to get one face a lifetime on immunosuppressive drugs to stop the body rejecting the new organ, drugs that increase the risk for infection, heart disease and diabetes.  

Dr. Everett Meyer, and his team at Stanford University, will use a combination of healthy donor stem cells and the patient’s own regulatory T cells (Tregs), to train the patient’s immune system to accept the transplanted kidney and eliminate the need for immunosuppressive drugs.

The initial group targeted in this clinical trial are people with what are called HLA-mismatched kidneys. This is where the donor and recipient do not share the same human leukocyte antigens (HLAs), proteins located on the surface of immune cells and other cells in the body. Around 50 percent of patients with HLA-mismatched transplants experience rejection of the organ.

In his application Dr. Meyer said they have a simple goal: “The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off immunosuppressive drugs will improve due to reduction in side effects associated with these drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.”

A Bridge to the future for stem cell students

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Students present their research finding at the 2016 CIRM Bridges conference

One of the programs people here at CIRM love is our Bridges to Stem Cell Research Awards. These are given to undergraduate and master’s level college students, to train the next generation of stem cell scientists. How good a program is it? It’s terrific. You don’t have to take my word for it. Just read this piece by a great stem cell champion, Don Reed. Don is the author of two books about CIRM, Stem Cell Battles and California Cures! so he clearly knows what he’s talking about.

ADVENTURES ON “BRIDGES”: Humboldt State Stem Cell Research

By Don C. Reed

Imagine yourself as a California college student, hoping to become a stem cell researcher. Like almost all students you are in need of financial help, and so (let’s say) you asked your college counselor if there were any scholarships available.

To your delight, she said, well, there is this wonderful internship program called Bridges, funded by the California Institution for Regenerative Medicine (CIRM) which funds training in stem cell biology and regenerative medicine — and so, naturally, you applied…

If you were accepted, how might your life change?

https://www.cirm.ca.gov/our-funding/research-rfas/bridges

After doing some basic training at the college, you would receive a grant (roughly $40,000) for a one-year internship at a world-renowned stem cell research facility. What an incredible leap forward in your career, hands-on experience (essentially a first job, great “experience” for the resume) as well an expert education.

Where are the 14 California colleges participating in this program? Click below:

https://www.cirm.ca.gov/our-funding/funded-institutions

Let’s take a look at one of these college programs in action: find out what happened to a few of the students who received a Bridges award, crossing the gap between studying stem cell research and actually applying it.

HSU information is courtesy of Dr. Amy Sprowles, Associate Professor of Biological Sciences and Co-Director of the Bridges program at Humboldt State University (HSU), 279 miles north of San Francisco.

Dr. Amy Sprowles

“The HSU Bridges program”, says Dr. Sprowles, “was largely developed by four people: Rollin Richmond, then HSU President, who worked closely with Susan Baxter, Executive Director of the CSU Program for Education and Research in Biotechnology, to secure the CIRM Bridges initiative; HSU Professor of Biological Sciences Jacob Varkey, who pioneered HSU’s undergraduate biomedical education program”, and Sprowles herself, at the time a lecturer with a PhD in Biochemistry.

The program has two parts: a beginning course in stem cell research, and a twelve-month internship in a premiere stem cell research laboratory. For HSU, these are at Stanford University, UC Davis, UCSF, or the Scripps Research Institute.

Like all CIRM Bridges programs, the HSU stem cell program is individually designed to suit the needs of its community.

Each of the 15 CIRM Bridges Programs fund up to ten paid internships, but the curriculum and specific activities of each are designed by their campus directors. The HSU program prepares Bridges candidates by requiring participation in a semester-long lecture and stem cell biology laboratory course before selection for the program: a course designed and taught by Sprowles since its inception.

She states, “The HSU pre-internship course ensures our students are trained in fundamental scientific concepts, laboratory skills and professional behaviors before entering their host laboratory. We find this necessary since, unlike the other Bridges campuses, we are 300+ miles away from the internship sites and are unable to fully support this kind of training during the experience. It also provides additional insights about the work ethic and mentoring needs of the individuals we select that are helpful in placing and supporting our program participants”.

How is it working?

Ten years after it began, 76 HSU students have completed the CIRM Bridges program at HSU. Of those, the overwhelming majority (over 85%) are committed to careers in regenerative medicine: either working in the field already, or continuing their education toward that goal.

But what happened to their lives? Take a brief look at the ongoing careers of a “Magnificent Seven” HSU Bridges scientists:

CARSTEN CHARLESWORTH: “Spurred by the opportunity to complete a paid internship at a world class research institution in Stem Cell Biology, I applied to the Humboldt CIRM Bridges program, and was lucky enough to be accepted. With a keen interest in the developing field of genome editing and the recent advent of the CRISPR-Cas9 system I chose to intern in the lab of a pioneer in the genome editing field, Dr. Matthew Porteus at Stanford, who focuses in genome editing hematopoietic stem cells to treat diseases such as sickle cell disease. In August of 2018 I began a PhD in Stanford’s Stem Cell and Regenerative Medicine program, where I am currently a second-year graduate student in the lab of Dr. Hiro Nakauchi, working on the development of human organs in interspecies human animal chimeras. The success that I’ve had and my acceptance into Stanford’s world class PhD program are a direct result of the opportunity that the CIRM Bridges internship provided me and the excellent training and instruction that I received from the Humboldt State Biology Program.”

ELISEBETH TORRETTI: “While looking for opportunities at HSU, I stumbled upon the CIRM Bridges program. It was perfect- a paid internship at high profile labs where I could expand my research skills for an entire year… the best fit (was) Jeanne Loring’s Lab at the Scripps Research Institute in La Jolla, CA. Dr. Loring is one of the premiere stem cell researchers in the world… (The lab’s) main focus is to develop a cure for Parkinson’s disease. (They) take skin cells known as fibroblasts and revert them into stem cells. These cells, called induced pluripotent stem cells (iPSCs) can then be differentiated into dopaminergic neurons and transplanted into the patient…. My project focused on a different disease: adenylate-cyclase 5 (ADCY5) — related dyskinesia. During my time at Dr. Loring’s lab I learned incredibly valuable research skills. I am now working in a mid-sized biotch company focusing on cancer research. I don’t think that would be possible in a competitive area like San Diego without my experience gained through the CIRM Bridges program.”

BRENDAN KELLY: “After completing my CIRM internship in Dr. Marius Wernig’s lab (in Stanford), I began working at a startup company called I Peace. I helped launch this company with Dr. Koji Tanabe, whom I met while working in my host lab. I am now at Cardiff University in Wales working on my PhD. My research involves using patient iPSC derived neurons to model Huntington’s disease. All this derived from my opportunity to partake in the CIRM-Bridges program, which opened doors for me.”

SAMANTHA SHELTON: “CIRM Bridges provided invaluable hands-on training in cell culture and stem cell techniques that have shaped my future in science. My CIRM internship in John Rubenstein’s Lab of Neural Development taught me amazing laboratory techniques such as stem cell transplantation as well as what goes into creating a harmonious and productive laboratory environment. My internship projects led to my first co-first author publication.

After my Bridges internship, I joined the Graduate Program for Neuroscience at Boston University. My PhD work aims to discover types of stem cells in the brain and how the structure of the brain develops early in life. During this time, I have focused on changes in brain development after Zika virus infection to better understand how microcephaly (small skulls and brains, often a symptom of Zika-DR) is caused. There is no doubt that CIRM not only made me a more competitive candidate for a doctoral degree but also provided me with tools to progress towards my ultimate goal of understanding and treating neurological diseases with stem cell technologies.”

DU CHENG: “Both my academic and business tracks started in the CIRM-funded…fellowship (at Stanford) where I invented the technology (the LabCam Microscope adapter) that I formed my company on (iDU Optics LLC). The instructor of the class, Dr. Amy Sprowles, encouraged me to carry on the idea. Later, I was able to get in the MD-PhD program at Weill Cornell Medical College because of the invaluable research experiences CIRM’s research program provided me. CIRM initiated the momentum to get me where I am today. Looking back, the CIRM Bridges Program is an instrumental jump-starter on my early career… I would not remotely be where I am without it.…”

CODY KIME: “Securing a CIRM grant helped me to take a position in the Nobel Prize winning Shinya Yamanaka Lab at the Gladstone Institutes, one of the most competitive labs in the new field of cell reprogramming. I then explored my own reprogramming interests, moving to the Kyoto University of Medicine, Doctor of Medical Sciences Program in Japan, and building a reprogramming team in the Masayo Takahashi Lab at RIKEN. My studies explore inducing cells to their highest total potential using less intrusive means and hacking the cell program. My systems are designed to inform my hypotheses toward a true お好みの細胞 (okonomi no cybo) technology, meaning ‘cells as you wish’ in Japanese, that could rapidly change any cell into another desired cell type or tissue.”

Sara Mills

SARA MILLS: “The CIRM Bridges program was the key early influencer which aided in my hiring of my first industry position at ViaCyte, Inc. Also a strongly CIRM funded institution, I was ultimately responsible for the process development of the VC-01™ fill, finish processes and cGMP documentation development. Most recently, with over two years at the boutique consulting firm of Dark Horse Consulting, Inc., I have been focusing on aseptic and cGMP manufacturing process development, risk analysis, CMC and regulatory filings, facility design and project management to advise growing cell and gene therapy companies, worldwide.”

Like warriors fighting to save lives, these young scientists are engaged in an effort to study and defeat chronic disease. It is to be hoped the California stem cell program will have its funding renewed, so the “Bridges” program can continue.

For more information on the Bridges program, which might help a young scientist (perhaps yourself) cut and paste the following URL:

https://www.cirm.ca.gov/our-impact/internship-programs

One closing paragraph perhaps best sums up the Bridges experience:

“During my CIRM Bridges training in Stanford University, I was fortunate to work with Dr. Jill Helms, who so patiently mentored me on research design and execution. I ended up publishing 7 papers with her during the two-year CIRM internship and helped making significant progress of turning a Stem Cell factor into applicable therapeutic form, that is currently in preparation for clinical trial by a biotech company in Silicon Valley. I also learned from her how to write grants and publications, but more importantly, (to) never limit your potential by what you already know.” — Du Cheng

Stem Cell Agency celebrates 50 clinical trials with patient #1

Yesterday the CIRM Board approved funding for our 50th clinical trial (you can read about that here) It was an historic moment for us and to celebrate we decided to go back in history and hear from the very first person to be treated in a CIRM-funded clinical trial. Rich Lajara was treated in the Geron clinical trial after experiencing a spinal cord injury, thus he became CIRM’s patient #1. It’s a badge he says he is honored to wear. This is the speech Rich made to our Board.

Rich Lajara

Hello and good afternoon everyone. It’s an honor to be here today as the 50th clinical trial has been officially funded by CIRM. It was feels like it was just yesterday that I was enrolled into the first funded clinical trial by CIRM and in turn became California’s’ 1st embryonic stem cell patient.

I became paralyzed from the waist down in September 2011. It was Labor Day and I was at a river with some close friends. There was this natural granite rock slide feature next to a waterfall, it was about 60 feet long; all you had to do was get a bucket of water to get the rocks wet and slide down into a natural pool. I ended up slipping and went down head first backwards but was too far over and I slid off a 15’ ledge where the waterfall was. I was pulled from the water and banged up pretty bad. Someone said “look at that deformity on his back” and tapped my leg and asked if I could feel that. I knew immediately I was paralyzed. I thought this was the end, little did I know this was just the beginning. I call it being in the wrong place at the right time.

So, after a few days in the hospital of course everyone, as well as myself, wanted a cure. We quickly learned one didn’t exist. A close family friend had been making phone calls and was able to connect with the Christopher & Dana Reeve Foundation and learned about a clinical trial with “stem cells”. One of my biggest question was how any people have done this? “Close to none”, I was told.

I was also told I most likely would have no direct benefit as this was a safety trial? So why do it at all? Obviously at that time I was willing to overlook the “most likely” part because I was willing to do anything to try and get my normal life back.

Looking back the big picture was laying the ground work for others like Kris or Jake (two people enrolled in a later version of this trial). At the time I had no clue that what I was doing would be such a big deal. The data collected from me would end up being priceless. It’s stories like Jake’s and Kris’ that make me proud and reinforce my decision to have participated in California’s first stem cell clinical trial funded by prop 71.

Like I said earlier it was just the beginning for me. A couple of years later I became a patient advocate working with Americans for Cures. I have been able to meet many people in the stem cell industry and love to see the glow in their face when they learn I was California’s first embryonic stem cell patient.

I can’t even fathom all the year’s of hard work and countless hours of research that had lead up to my long anticipated surgery, but when I see their glowing smile I know they knew what it took.

I also enjoy sharing my story and bridging the gap between myths and facts about stem cells, or talking to students and helping inspire the next generation that will be in the stem cell industry.  As a matter of fact, I have 13 year old sister, Maddie, dead set on being a neurosurgeon.

Fast forward to today. Life in a wheelchair is not exactly a roll in the park (no pun intended) but I have grown accustomed to the new normal. Aside from some neuropathic pain, life is back on track.

Not once did I feel sorry for myself, I was excited to be alive. Sure I have bad days but don’t we all.

In the last 14 years CIRM has funded 50 human clinical trials, published around 2750 new peer-reviewed scientific discoveries, and they’ve transformed California into the world leader in stem cell research. As I look around the posters on the wall, of the people whose lives have been transformed by the agency, I can’t help but be struck by just how much has been achieved in such a short period of time.

While my journey might not yet be over, Evie and 40 other children like her, (children born with SCID) will never remember what it was like to live with the horrible condition they were born with because they have been cured thanks to CIRM. There are hundreds of others whose lives have been transformed because of work the agency has funded.

CIRM has proven how much can be achieved if we invest in cutting-edge medical research.

As most of you here probably know CIRM’s funding from Proposition 71 is about to run out. If I had just one message I wanted people to leave with today it would be this. Everyone in this room knows how much CIRM has done in a little over a decade and how many lives have been changed because of its existence. We have the responsibility to make sure this work continues. We have a responsibility to make sure that the stories we’ve heard today are just the beginning.

I will do everything I can to make sure the agency gets refunded and I hope that all of you will join me in that fight. I’m excited for the world of stem cells, particularly in California, and can’t wait to see what’s on the horizon.

 

Stem Cell Agency Board Approves 50th Clinical Trial

2018-12-13 01.18.50Rich Lajara

Rich Lajara, the first patient treated in a CIRM-funded clinical trial

May 4th, 2011 marked a landmark moment for the California Institute for Regenerative Medicine (CIRM). On that day the Stem Cell Agency’s Board voted to invest in its first ever clinical trial, which was also the first clinical trial to use cells derived from embryonic stem cells. Today the Stem Cell Agency reached another landmark, with the Board voting to approve its 50th clinical trial.

“We have come a long way in the past seven and a half years, helping advance the field from its early days to a much more mature space today, one capable of producing new treatments and even cures,” says Jonathan Thomas, JD, PhD, Chair of the CIRM Board. “But we feel that in many ways we are just getting started, and we intend funding as many additional clinical trials as we can for as long as we can.”

angiocrinelogo

The project approved today awards almost $6.2 million to Angiocrine Bioscience Inc. to see if genetically engineered cells, derived from cord blood, can help alleviate or accelerate recovery from the toxic side effects of chemotherapy for people undergoing treatment for lymphoma and other aggressive cancers of the blood or lymph system.

“This is a project that CIRM has supported from an earlier stage of research, highlighting our commitment to moving the most promising research out of the lab and into people,” says Maria T. Millan, MD, President & CEO of CIRM. “Lymphoma is the most common blood cancer and the 6th most commonly diagnosed cancer in California. Despite advances in therapy many patients still suffer severe complications from the chemotherapy, so any treatment that can reduce those complications can not only improve quality of life but also, we hope, improve long term health outcomes for patients.”

The first clinical trial CIRM funded was with Geron, targeting spinal cord injury. While Geron halted the trial for business reasons (and returned the money, with interest) the mantle was later picked up by Asterias Biotherapeutics, which has now treated 25 patients with no serious side effects and some encouraging results.

Rich Lajara was part of the Geron trial, the first patient ever treated in a CIRM-funded clinical trial. He came to the CIRM Board meeting to tell his story saying when he was injured “I knew immediately I was paralyzed. I thought this was the end, little did I know this was just the beginning. I call it being in the wrong place at the right time.”

When he learned about the Geron clinical trial he asked how many people had been treated with stem cells. “Close to none” he was told. Nonetheless he went ahead with it. He says he has never regretted that decision, knowing it helped inform the research that has since helped others.

Since that first trial the Stem Cell Agency has funded a wide range of projects targeting heart disease and stroke, cancer, diabetes, HIV/AIDS and several rare diseases. You can see the full list on the Clinical Trials Dashboard page on our website.

Rich ended by saying: “CIRM has proven how much can be achieved if we invest in cutting-edge medical research. As most of you here probably know, CIRM’s funding from Proposition 71 is about to run out. If I had just one message I wanted people to leave with today it would be this, I will do everything I can to make sure the agency gets refunded and I hope that all of you will join me in that fight. I’m excited for the world of stem cells, particularly in California and can’t wait to see what’s on the horizon.”

lubinbert-mug

The CIRM Board also took time today to honor Dr. Bert Lubin, who is stepping down after serving almost eight years on the Board.

When he joined the Board in February, 2011 Dr. Lubin said: “I hope to use my position on this committee to advocate for stem cell research that translates into benefits for children and adults, not only in California but throughout the world.”

Over the years he certainly lived up to that goal. As a CIRM Board member he has supported research for a broad range of unmet medical needs, and specifically for curative treatments for children born with a rare life-threatening conditions such as Sickle Cell Disease and Severe Combined Immunodeficiency (SCID) as well as  treatments to help people battling vision destroying diseases.

As the President & CEO of Children’s Hospital Oakland (now UCSF Benioff Children’s Hospital Oakland) Dr. Lubin was a leader in helping advance research into new treatments for sickle cell disease and addressing health disparities in diseases such as asthma, diabetes and obesity.

Senator Art Torres said he has known Dr. Lubin since the 1970’s and in all that time has been impressed by his devotion to patients, and his humility, and that all Californians should be grateful to him for his service, and his leadership.

Dr. Lubin said he was “Really grateful to be on the Board and I consider it an honor to be part of a group that benefits patients.”

He said he may be stepping down from the CIRM Board but that was all: “I am going to retire the word retirement. I think it’s a mistake to stop doing work that you find stimulating. I’m going to repurpose the rest of my life, and work to make sure the treatments we’ve helped develop are available to everyone. I am so proud to be part of this. I am stepping down, but I am devoted to doing all I can to ensure that you get the resources you need to sustain this work for the future.”

Living with sickle cell disease: one person’s story of pain and prejudice and their hopes for a stem cell therapy

Whenever we hold an in-person Board meeting at CIRM we like to bring along a patient or patient advocate to address the Board. Hearing from the people they are trying to help, who are benefiting or may benefit from a therapy CIRM is funding, reminds them of the real-world implications of the decisions they make and the impact they have on people’s lives.

At our most recent meeting Marissa Cors told her story.

Marissa at ICOC side view copy

Marissa Cors addressing the CIRM Board

My name is Marissa Cors, I have sickle cell disease. I was diagnosed with sickle cell disease at six months of age. I am now 40. Sickle cell has been a part of my life every day of my life.

The treatments you are supporting and funding here at CIRM are very important. They offer a potential cure to a disease that desperately needs one. I want to tell you just how urgently people with sickle cell need a cure.

I have been hospitalized so many times that my medical record is now more than 8 gigabytes. I have almost 900 pages in my medical record from my personal doctor alone.

I live with pain every day of my life but because you can’t see pain most people have no idea how bad it can be. The pain comes in two forms:

Chronic pain – this comes from the damage that sickle cell disease does to the body over many years. My right knee, my left clavicle, my lower back are all damaged because of the disease. I get chronic headaches. All these are the result of a lifetime of crisis.

Acute pain – this is the actual crisis that can’t be controlled, where the pain is so intense and the risk of damage to my organs so great that it requires hospitalization. That hospitalization can result in yet more pain, not physical but emotional and psychological pain.

But those are just the simple facts. So, let me tell you what it’s really like to live with sickle cell disease.

Marissa at ICOC front, smiling

It means being in a constant state of limbo and a constant state of unknown because you have no idea when the next crisis is going to come and take over and you have to stop your life. You have absolutely no idea how bad the pain will be or how long it will last.

It is a constant state of frustration and upset and even a constant state of guilt because it is your responsibility to put in place all the safety nets and plans order to keep life moving as normally as possible, not just for you but for everyone else around you. And you know that when a crisis comes, and those plans get ripped up that it’s not just your own life that gets put on hold while you try to deal with the pain, it’s the lives of those you love.

It means having to put your life on hold so often that it’s hard to have a job, hard to have a career or lead a normal life. Hard to do the things everyone else takes for granted. For example, in my 30’s, while all my friends from home and college were building careers and getting married and having families, I was in a cancer ward trying to stay alive, because that’s where they put you when you have sickle cell disease. The cancer ward.

People talk about new medications now that are more effective at keeping the disease under control. But let me tell you. As a black woman walking into a hospital Emergency Room saying I am having a sickle cell crisis and need pain medications, and then naming the ones I need, too often I don’t get treated as a patient, I get treated as a drug addict, a drug seeker.

Even when the doctors do agree to give me the medications I need they often act in a way that clearly shows they don’t believe me. They ask, “How do we know this is a crisis, why is it taking you so long for the medication to take effect?” These are people who spent a few days in medical school reading from a textbook about sickle cell disease. I have spent a lifetime living with it and apparently that’s still not enough for them to trust that I do know what I am talking about.

That’s when I usually say, “Goodbye and don’t forget to send in your replacement doctor because I can’t work with you.”

I have had doctors take away my medication because they wanted to see how I would react without it.

If I dare to question what a doctor or nurse does, they frequently tell me they have to go and take care of other patients who are really sick, not like me.

Even when I talk in my “nice white lady” voice they still treat me and call me “an angry black girl”. Girl. I’m a 40 year old woman but I get treated like a child.

It’s hard to be in the hospital surrounded by doctors and nurses and yet feel abandoned by the medical staff around you.

This month alone 25 people have died from sickle cell in the US. It’s not because we don’t have treatments that can help. It’s due to negligence, not getting the right care at the right time.

I know the work you do here at CIRM won’t change those attitudes. But maybe the research you support could find a cure for sickle cell, so people like me don’t have to endure the pain, the physical, emotional and spiritual pain, that the disease brings every day.

You can read about the work CIRM is funding targeting sickle cell disease, including two clinical trials, on this page on our website.

Stem Cell Agency Invests in New Immunotherapy Approach to HIV, Plus Promising Projects Targeting Blindness and Leukemia

HIV AIDS

While we have made great progress in developing therapies that control the AIDS virus, HIV/AIDS remains a chronic condition and HIV medicines themselves can give rise to a new set of medical issues. That’s why the Board of the California Institute for Regenerative Medicine (CIRM) has awarded $3.8 million to a team from City of Hope to develop an HIV immunotherapy.

The City of Hope team, led by Xiuli Wang, is developing a chimeric antigen receptor T cell or CAR-T that will enable them to target and kill HIV Infection. These CAR-T cells are designed to respond to a vaccine to expand on demand to battle residual HIV as required.

Jeff Sheehy

CIRM Board member Jeff Sheehy

Jeff Sheehy, a CIRM Board member and patient advocate for HIV/AIDS, says there is a real need for a new approach.

“With 37 million people worldwide living with HIV, including one million Americans, a single treatment that cures is desperately needed.  An exciting feature of this approach is the way it is combined with the cytomegalovirus (CMV) vaccine. Making CAR T therapies safer and more efficient would not only help produce a new HIV treatment but would help with CAR T cancer therapies and could facilitate CAR T therapies for other diseases.”

This is a late stage pre-clinical program with a goal of developing the cell therapy and getting the data needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial.

The Board also approved three projects under its Translation Research Program, this is promising research that is building on basic scientific studies to hopefully create new therapies.

  • $5.068 million to University of California at Los Angeles’ Steven Schwartz to use a patient’s own adult cells to develop a treatment for diseases of the retina that can lead to blindness
  • $4.17 million to Karin Gaensler at the University of California at San Francisco to use a leukemia patient’s own cells to develop a vaccine that will stimulate their immune system to attack and destroy leukemia stem cells
  • Almost $4.24 million to Stanford’s Ted Leng to develop an off-the-shelf treatment for age-related macular degeneration (AMD), the leading cause of vision loss in the elderly.

The Board also approved funding for seven projects in the Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Application Title Institution CIRM Committed Funding
DISC2-10979 Universal Pluripotent Liver Failure Therapy (UPLiFT)

 

Children’s Hospital of Los Angeles $1,297,512

 

DISC2-11105 Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer

 

Stanford $1,415,016
DISC2-10973 Small Molecule Proteostasis Regulators to Treat Photoreceptor Diseases

 

U.C. San Diego $1,160,648
DISC2-11070 Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs

 

Scripps $1,827,576
DISC2-11183 A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs

 

University of Southern California $833,971
DISC2-11199 Modulation of the Wnt pathway to restore inner ear function

 

Stanford $1,394,870
DISC2-11109 Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome

 

Stanford $1,415,016

Finally, the Board approved the Agency’s 2019 research budget. Given CIRM’s new partnership with the National Heart, Lung, Blood Institute (NHLBI) to accelerate promising therapies that could help people with Sickle Cell Disease (SCD) the Agency is proposing to set aside $30 million in funding for this program.

barbara_lee_official_photo

Congresswoman Barbara Lee (D-CA 13th District)

“I am deeply grateful for organizations like CIRM and NHLBI that do vital work every day to help people struggling with Sickle Cell Disease,” said Congresswoman Barbara Lee (D-CA 13th District). “As a member of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, I know well the importance of this work. This innovative partnership between CIRM and NHLBI is an encouraging sign of progress, and I applaud both organizations for their tireless work to cure Sickle Cell Disease.”

Under the agreement CIRM and the NHLBI will coordinate efforts to identify and co-fund promising therapies targeting SCD.  Programs that are ready to start an IND-enabling or clinical trial project for sickle cell can apply to CIRM for funding from both agencies. CIRM will share application information with the NHLBI and CIRM’s Grants Working Group (GWG) – an independent panel of experts which reviews the scientific merits of applications – will review the applications and make recommendations. The NHLBI will then quickly decide if it wants to partner with CIRM on co-funding the project and if the CIRM governing Board approves the project for funding, the two organizations will agree on a cost-sharing partnership for the clinical trial. CIRM will then set the milestones and manage the single CIRM award and all monitoring of the project.

“This is an extraordinary opportunity to create a first-of-its-kind partnership with the NHLBI to accelerate the development of curative cell and gene treatments for patients suffering with Sickle Cell Disease” says Maria T. Millan, MD, President & CEO of CIRM. “This allows us to multiply the impact each dollar has to find relief for children and adults who battle with this life-threatening, disabling condition that results in a dramatically shortened lifespan.  We are pleased to be able to leverage CIRM’s acceleration model, expertise and infrastructure to partner with the NHLBI to find a cure for this condition that afflicts 100,000 Americans and millions around the globe.”

The budget for 2019 is:

Program type 2019
CLIN1 & 2

CLIN1& 2 Sickle Cell Disease

$93 million

$30 million

TRANSLATIONAL $20 million
DISCOVER $0
EDUCATION $600K

 

 

Stem cell summer: high school students document internships via social media, Part 3

Today we share our third and final pair of social media awards from CIRM’s 2018 SPARK (Summer Program to Accelerate Regenerative medicine Knowledge) program, a 6-12 week summer internship program that provides hands-on stem cell research training to high school students throughout California.

AnthonyTan

CIRM SPARK 2018 Best Instagram Post winner by Caltech SPARK intern Anthony Tan

As part of their curriculum, the students were asked to write a blog and to post Instagram photos (follow #cirmsparklab) to document their internship experiences. Several CIRM team members selected their favorite entries and presented awards to the winning interns at the SPARK Student Conference earlier this month at UC Davis.

The two winners featured today are Caltech SPARK student, Anthony Tan – a senior at John A. Rowland High School – one of the Instagram Award winners (see his Instagram post above) and UCSF SPARK student Gennifer Hom – a senior at Ruth Asawa School of the Arts – one of the Blog Award winners. Read her blog below. (To learn about the other 2018 social media winners, see our previous blog posts here and here.)

Best Blog Award:
My SPARK 2018 summer stem cell research internship experience
By Gennifer Hom

genniferhom

Gennifer Hom

When I was seven, I remember looking up at the stars, I stared hard at the moon through my car window, thinking that it only revolves around me as it followed me home. I later learned in class that we rotate around the sun, as gravity holds the spinning planets in place, simultaneously, the moon revolves around the earth. Out of nowhere, I abruptly felt an actual light bulb switched on above my head once I learned how day and night came. Overcome with curiosity,“ Where did the Big Bang take place? When will my Big Bang happen?”

My interest dissipated as I entered into my high school career. I was struck with incoherence, an inconsistency to my thoughts, as I leaned my shoulder against the wall—for I had already decided to let my fatigue to take over. I felt lacking, unconfident in my abilities even to solve a simple balance chemical equation in chemistry class. Science was not my forte. I could never see myself working in a lab setting.

Still, a spark within me still held onto that childhood curiosity of mine. I remember sitting on the bus on my way to school reading about stem cells, which were fascinating to me. We can use these little cells for so many scientific research.

My Big Bang unfolded when I was accepted into the UCSF SEP internship program. I
studied the human-specific population of cortical neural stem cells and evaluated the signaling mechanisms that govern the formation of their identity. Through my performance, I am also contributing to this phenomenal study, helping my community by potentially providing information to help cure mental illnesses. At times, the results of our data did not come out as we wanted it to be. The staining went wrong, and the images were lacking. I would have to repeat the experiment or troubleshoot on the spot continually. However, it’s all a learning process. Even if I do get beautiful image stainings, I still need to repeat the experiments to confirm my results.

Learning was not the only side that is needed under this program. CIRM encouraged us to share our internship experiences on social media. I posted once a week on my studies, what I’ve learned, and how I could teach my viewers about this new research I am performing. I remember in one of the first few meetings we had, where we had to share our research with our peers, “ I can actually understand your studies,” a friend of mine claimed.

I felt powerful, in a sense, that I was able to communicate my knowledge to others to help them understand and teach my study. When I talk to my family and friends about my summer, I feel confident in my ability to comprehend these complex ideas. I could see myself researching, engineering, and fighting for a solution. I want to find the best form of gene therapy, and map each neuron of the brain. Through this two month program, science has become a new passion for me, a cornerstone of my new academic pursuits. It strengthened my theoretical knowledge and gave me an experience where I witnessed the real world laboratory setting. Not only did I learn the fundamental techniques of immunohistochemistry and microscopy, but I was able to receive encouraging advice from the scientists in the Kriegsteins lab and especially my mentor, Madeline Andrews. The experience in a lab comforted me by the idea of the never-ending changes that lured me to a world of thought and endless potential.

Stem cell summer: high school students document internships via social media, Part 2

Well, just like that, summer vacation is over. Most kids in California are back in school now and probably one of the first questions they’ll ask their friends is, “what did you do this summer?”. For 58 talented high school students, their answer will be, “I became a stem cell scientist.”

Best Instagram Post Award: Mia Grossman

Those students participated in a CIRM-funded internship called the Summer Program to Accelerate Regenerative medicine Knowledge, or SPARK for short, with seven programs throughout Northern and Southern California which include Caltech, Cedars-Sinai, City of Hope, Stanford, UC Davis, UCSF and the UCSF Benioff Children’s Hospital Oakland. Over the course of about 8 eight weeks, the interns gained hands-on training in stem cell research at some of the leading research institutes in California. Last week, they all met for the annual SPARK conference, this year at the UC Davis Betty Irene Moore School of Nursing, to present their research results and to hear from expert scientists and patient advocates.

As part of their curriculum, the students were asked to write a blog and to post Instagram photos (follow #cirmsparklab) to document their internship experiences. Several CIRM team member selected their favorite entries and presented awards to the winning interns at the end of the conference. We featured two of the winners in a blog from last week.

Our two winners featured today are Cedars-Sinai SPARK student, Mia Grossman – a senior at Beverly Hills High School – one of the Instagram Award winners (see her looping video above) and UC Davis SPARK student Anna Guzman – a junior at Sheldon High School – one of the Blog Award winners. Here’s her blog:

The Lab: A Place I Never Thought I’d Be
By Anna Guzman

AnnaGuzman

Anna Guzman

My CIRM SPARK journey started long before I ever stepped foot in the Institute for Regenerative Cures at UC Davis. Instead, my journey started two years earlier, when my older sister came home from the same internship with stories of passaged cells, images of completed western blots, and a spark in her eye when she described the place she had come to love. Barely 14 years old, I listened wide-eyed as my sister told us about the place she disappeared to each morning, stories of quirky professors, lovable mentors, and above all, the brilliant flame that everyone in her lab shared for learning. But even as she told her stories around the dinner table, I imagined this cold place where my charismatic, intelligent, and inquisitive sister was welcomed. I imagined the chilling concentration of dozens of geniuses bent over their work, of tissue culture rooms where every tiny movement was a potential disaster, and above all, of a labyrinth of brilliant discoveries and official sounding words with the door securely locked to 16 year old girls – girls who had no idea what they wanted to do with their life, who couldn’t confidently rattle words like “CRISPR,” “mesenchymal” and “hematopoietic” off their tongues. In short, this wasn’t a place for me.

But somehow I found myself applying for the CIRM SPARK internship. Seconds after I arrived for my first day at the place I was sure I would not belong, I realized how incorrect my initial assumption of the lab was. Instead of the intimidating and sophisticated environment filled with eye-rolling PhDs who scoffed at the naïve questions of a teenager, I found a room filled with some of the kindest, funniest, warmest people I had ever met. I soon found that the lab was a place of laughter and jokes across bays, a place of smiles in the hallways and mentors who tirelessly explained theory after theory until the intoxicating satisfaction of a lightbulb sparked on inside my head. The lab was a place where my wonderful mentor Julie Beegle patiently guided me through tissue culture, gently reminding me again and again how to avoid contamination and never sighing when I bubbled up the hemocytometer, miscalculated transduction rates, or asked question after question after question. Despite being full of incredibly brilliant scholars with prestigious degrees and publications, the lab was a place where I was never made to feel small or uneducated, never made to feel like there was something I couldn’t understand. So for me, the lab became a place where I could unashamedly fuel my need to understand everything, to ask hundreds of questions until the light bulbs sputtered on and a spark, the same spark that had glowed in the eyes of my sister years ago, burned brightly. The lab became a place where it was always okay to ask why.

At moments towards the middle of the internship, when my nerves had dissolved into a foundation of tentative confidence, and I had started to understand the words that tumbled out of my mouth, I’d be working in the biosafety cabinet or reading a protocol to my mentor and think, Wow. That’s Me. That’s me counting colonies and loading gels without the tell-tale nervous quiver of a beginner’s hand. That’s me explaining my project to another intern without an ambiguous question mark marring the end of the sentence. That’s me, pipetting and centrifuging and talking and understanding – doing all the things that I was certain that I would never be able to do. That’s the best thing that the CIRM SPARK internship has taught me. Being an intern in this wonderful place with these amazing people has taught me to be assured in my knowledge, unashamed in my pursuit of the answer, and confident in my belief that maybe I belong here. These feelings will stay with me as I navigate the next two years of high school and the beginning of the rest of my life. I have no doubt that I will feel unsure again, that I will question whether I belong and wonder if I am enough. But then I will remember how I felt here, confident, and unashamed, and assured in the place where I never thought I’d be.

It was not until the end of my internship, as I stood up to present a journal article to a collection of the very people who had once terrified me, that I realized the biggest thing I was wrong about two years ago. I was wrong when I assumed that this was a place where I would never belong. Instead, as I stood in front of this community of amazingly brilliant and kind people, my mouth forming words that I couldn’t have dreamed of understanding a month ago, I realized that this was precisely where I belonged. This was the place for me.