To Mend: (verb used with object) to make (something broken, worn, torn or otherwise damaged) whole, sound or usable by repairing.
It’s remarkable to believe, but today doctors literally have the tools to repair damaged cells. These tools are being used to treat people with diseases that were once incurable. The field of regenerative medicine has made tremendous progress in the last 15 years, but how did these tools come about and what is the experience of patients being treated with them?
These questions, and hopefully yours too, are going to be answered at the fourth annual CIRM Alpha Stem Cell Clinics Symposium on April 18, 2019 at the University of California at San Francisco.
The symposium is free, and the program is designed with patients and the public in mind, so don’t be shy and put your scientific thinking caps on! A complete agenda may be found here
Perhaps one of the most remarkable discoveries in the past decade are new tools that enable doctors to “edit” or correct a patient’s own DNA. DNA correction tools came about because of a remarkable string of scientific breakthroughs. The symposium will dive into this history and discuss how these tools are being used today to treat patients.
One specific example of the promise that DNA editing holds is for those with sickle cell disease (SCD), a condition where patients’ blood forming stem cells contain a genetic error that causes the disease. The symposium will describe how the CIRM Alpha Stem Cell Clinics Network, a series of medical centers across California whose focus is on stem cell clinical trials, are supporting work aimed at mending blood cells to cure debilitating diseases like SCD.
Doctors, nurses and patients involved with these trials will be telling their stories and describing their experiences. One important focus will be how Alpha Clinic teams are partnering with community members to ensure that patients, interested in new treatments, are informed about the availability of clinical trials and receive sufficient information to make the best treatment choices.
The fourth annual CIRM Alpha Stem Cell Clinics Symposium is an opportunity for patients, their families and the public to meet the pioneers who are literally mending a patients own stem cells to cure their disease.
It’s hard thinking of something as rare when one in 20 people are at risk of experiencing it in their lifetime. But that’s the situation with rare diseases. There are more than 7,000 of them and each affects under 200,000 people. In some cases they may only affect a few hundred people. But for each person that disease, though rare, poses a real threat. And that’s why Rare Disease Day was created.
Rare Disease Day is held on the last day of February each year. The goal is to raise awareness among the general public about the huge impact these diseases have on people’s lives. That impact is not just on the person with the disease but on the whole family who are often struggling just to get a diagnosis.
Every year groups around the world, from patients and patient advocacy organizations to researchers and policymakers, stage events to mark the day. This year there are more than 460 events being held in 96 countries, everywhere from Albania and Andora to Tunisia and Uruguay.
Here in the US many groups organize events at State Capitols
to educate elected officials and policy makers about the particular needs of
these communities and the promise that scientific
research holds to combat these conditions. Others have auctions to raise
funds for research or public debates to raise awareness.
Each event is unique in its own way because each represents many different diseases, many different needs, and many different stories. The goal of these events is to put a human face on each condition, to give it visibility, so that it is no longer something most people have never heard of, instead it becomes something that affects someone you may know or who reminds you of someone you know.
Here’s a video from Spain that does just that.
You can find a complete list of events being held around the
world to mark Rare
At CIRM we feel a special link to this day. That’s because many of the diseases we fund research into are rare diseases such as severe combined immunodeficiency (SCID), and ALS or Lou Gehrig’s disease, and Sickle Cell Disease.
These diseases affect relatively small numbers of patients so they often struggle to get funding for research. Because we do not have to worry about making a profit on any therapy we help develop we can focus our efforts on supporting those with unmet medical needs. And it’s paying off. Our support has already helped develop a therapy for SCID that has cured 40 children. We have two clinical trials underway for ALS or Lou Gehrig’s disease. We also have two clinical trials for Sickle Cell Disease and have reached a milestone agreement with the National Heart, Lung and Blood Institute (NHLBI) on a partnership to help develop a cure for this crippling and life-threatening disorder.
The hope is that events like Rare Disease Day let people
know that even though they have a condition that affects very few, that they
are not alone, but that they are part of a wider, global community, a community
committed to working to find treatments and cures for all of them.
Can cell therapy beat the most difficult diseases?
the question posed in a headline in National
Geographic. The answer; maybe, but it is going to take time and
article focuses on the use of iPS cells, the man-made equivalent of embryonic
stem cells that can be turned into any kind of cell or tissue in the body. The
reporter interviews Kemal
Malik, the member of the Board of Management for pharmaceutical giant Bayer who
is responsible for innovation. When it comes to iPS cells, it’s clear Malik is
a true believer in their potential.
“Because every cell
in our bodies can be produced from a stem cell, the applicability of cell
therapy is vast. iPSC technology has the potential to tackle some of the most
challenging diseases on the planet.”
he also acknowledges that the field faces some daunting challenges, including:
How to manufacture
the cells on a large scale without sacrificing quality and purity
How do you create
products that have a stable shelf life and can be stored until needed?
How do you handle
immune reactions if you are giving these cells to patients?
Malik remains confident we can overcome those challenges and realize the full
potential of these cells.
“I believe human
beings are on the cusp of the next big wave of pharmaceutical innovation. The
use of living cells to make people better.”
if to prove Malik right there was also news this week that researchers at
Japan’s Keio University have been given permission to start a clinical trial
using iPS cells to treat people with spinal cord injuries. This would be the
first of its kind anywhere in the world.
Japan launches iPSC clinical trial for spinal cord injury
article in Biospace
says that the researchers plan to treat four patients who have suffered varying
degrees of paralysis due to a spinal cord injury. They will take cells from the patients and,
using the iPS method, turn them into the kind of nerve cells found in the
spinal cord, and then transplant two million of them back into the patient. The
hope is that this will create new connections that restore movement and feeling
in the individuals.
trial is expected to start sometime this summer.
has already funded a first-of-its-kind clinical trial for spinal cord injury
Biotherapeutics. That clinical trial used embryonic stem cells
turned into oligodendrocyte progenitor cells – which develop into cells that support
and protect nerve cells in the central nervous system. We blogged about the
encouraging results from that trial here.
High fat diet drives
Finally today, researchers at Salk have uncovered a possible cause to the rise in colorectal cancer deaths among people under the age of 55; eating too much high fat food.
digestive system works hard to break down the foods we eat and one way it does
that is by using bile acids. Those acids don’t just break down the food,
however, they also break down the lining of our intestines. Fortunately, our
gut has a steady supply of stem cells that can repair and replace that lining.
Unfortunately, at least according to the team from Salk, mutations in these
stem cells can lead to colorectal cancer.
study, published in the journal Cell,
shows that bile acids affect a protein called FXR that is responsible for
ensuring that gut stem cells produce a steady supply of new lining for the gut
wall. When someone eats a high fat diet it upsets the balance of bile acids,
starting a cascade of events that help cancer develop and grow.
release Annette Atkins, a co-author of the study, says there is a
strong connection between bile acid and cancer growth:
“We knew that
high-fat diets and bile acids were both risk factors for cancer, but we weren’t
expecting to find they were both affecting FXR in intestinal stem cells.”
next time you are thinking about having that double bacon cheese burger for
lunch, you might go for the salad instead. Your gut will thank you. And it
might just save your life.
Imagine being told that your seemingly healthy newborn baby has a life-threatening disease. In a moment your whole world is turned upside down. That’s the reality for families with a child diagnosed with severe combined immunodeficiency (SCID). Children with SCID lack a functioning immune system so even a simple cold can prove fatal. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $3.7 million to develop a new approach that could help these children.
The funding will enable Stanford’s Dr. Judith Shizuru to complete
an earlier CIRM-funded Phase 1 clinical trial using a chemotherapy-free
transplant procedure for SCID.
The goal of the project is to replace SCID patients’ dysfunctional immune cells with healthy ones using a safer form of bone marrow transplant (BMT). Current BMT procedures use toxic chemotherapy to make space in the bone marrow for the healthy transplanted stem cells to take root and multiply. The Stanford team is testing a safe, non-toxic monoclonal antibody that targets and removes the defective blood forming stem cellsin order to promote the engraftment of the transplanted stem cells in the patient.
The funding is contingent on Dr. Shizuru raising $1.7
million in co-funding by May 1 of this year.
“This research highlights two of the things CIRM was
created to do,” says Maria T. Millan, MD, President & CEO of CIRM. “We fund
projects affecting small numbers of patients, something many organizations or
companies aren’t willing to do, and we follow those projects from the bench to
the bedside, supporting them every step along the way.”
Early testing has shown promise in helping patients and
it’s hoped that if this approach is successful in children with SCID it may
also open up similar BMT therapies for patients with other auto-immune diseases
such as multiple sclerosis, lupus or diabetes.
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.
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.
three experts are:
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 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 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.
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.”
For several years now, we have been trying to raise awareness about the risks posed by clinics offering unproven or unapproved stem cell therapies. At times it felt as if we were yelling into the wind, that few people were listening. But that’s slowly changing. A growing number of TV stations and newspapers are picking up the message and warning their readers and viewers. It’s a warning that is getting national exposure.
Why are we concerned about these clinics? Well, they claim
their therapies, which usually involve the patient’s own fat or blood cells,
can cure everything from arthritis to Alzheimer’s. However, they offer no
scientific proof, have no studies to back up their claims and charge patients
thousands, sometimes tens of thousands of dollars.
“If it sounds too good to be true, it is. There is no good scientific evidence the pricey treatments work, and there is growing evidence that some are dangerous, causing blindness, tumors and paralysis. Medical associations, the federal government and even Consumer Reports have all issued stern warnings to patients about the clinics.”
In Denver, the
ABC TV station recently did an in-depth interview with a local doctor who is
trying to get Colorado state legislators to take legal action against stem cell
clinics making these kinds of unsupported claims.
really out of control,” he told the station.
ABC7 did a series
of reports last year on the problem and that may be prompting this push for
a law warning consumers about the dangers posed by these unregulated treatments
which are advertised heavily online, on TV and in print.
there is already one law on the books attempting to warn consumers about these
clinics. CIRM worked with State Senator Ed Hernandez to get that passed (you can read about that here)
and we are continuing to support even stronger measures.
And the NBC TV
station in San Diego recently reported on the rise of stem cell clinics around
the US, a story that was picked up by the networks and run on the NBC
One of the critical
elements in helping raise awareness about the issue has been the work done by Paul
Knoepfler and Leigh Turner in identifying how many of these clinics there are
around the US. Their report, published in the journal Cell
Stem Cell, was the first to show how big the problem is. It attracted
national attention and triggered many of the reports that followed.
It is clear
momentum is building and we hope to build on that even further. Obviously, the
best solution would be to have the Food and Drug Administration (FDA) crack
down on these clinics, and in some cases they have. But the FDA lacks the
manpower to tackle all of them.
That’s where the
role of the media is so important. By doing stories like these and raising
awareness about the risks these clinics pose they can hopefully help many
patients avoid treatments that will do little except make a dent in their
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…
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:
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.
“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: “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:
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
Cystinosis is one of those diseases most people have never heard of and should be very grateful they haven’t. It’s rare – affecting only around 500 children and young adults in the US and just 2,000 people worldwide – but it’s nasty. Up to now the treatments for it have been very limited. But a new clinical trial, just given the go-ahead by the Food and Drug Administration (FDA), could help change that.
Cystinosis usually strikes children before they are two years old and can lead to end stage kidney failure before their tenth birthday. It is caused by a genetic mutation that allows an amino acid, cysteine, to build up in and damage the kidneys, eyes, liver, muscles, pancreas and brain.
There is one approved therapy, cysteamine, but this only delays progression of the disease, has severe side effects and people taking it still require kidney transplants, and develop diabetes, neuromuscular disorders and hypothyroidism.
All those are reasons why, in September 2016, the CIRM Board approved $5.2 million for U.C. San Diego researcher Stephanie Cherqui, Ph.D. and her team to try a different approach. Their goal is to take blood stem cells from people with cystinosis, genetically-modify them to remove the mutation that causes the disease, then return them to the patient. The hope is that the modified blood stem cells will create a new, healthy, blood system free of the disease.
Results from pre-clinical work testing this approach in mice have been so encouraging that the FDA has given the go-ahead for that work to now be tested in people.
In a news release Nancy Stack, the Founder and President of the Cystinosis Research Foundation (CRF), the largest provider of grants for cystinosis research in the world, says this is exciting news for a community that has been waiting for a breakthrough:
“We are thrilled that CRF’s dedication to funding Dr. Cherqui’s work has resulted in FDA approval for the first-ever stem cell and gene therapy treatment for individuals living with cystinosis. This approval from the FDA brings us one step closer to what we believe will be a cure for cystinosis and will be the answer to my daughter Natalie’s wish made fifteen years ago, ‘to have my disease go away forever.’ We are so thankful to our donors and our cystinosis families who had faith and believed this day would come.”
Dr. Cherqui says if this is successful it could help more than just people with cystinosis:
“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. If so, CRF, through their years of support will have helped an untold number of patients with untreatable, debilitating diseases.”
By any standards Dr. Diana Farmer is a determined woman who doesn’t let setbacks and failure deter her. As a fetal and neonatal surgeon, and the chair of the Department of Surgery at UC Davis Health, Dr. Farmer has spent years trying to develop a cure for spina bifida. She’s getting closer.
Dr. Farmer and her partner in this research, Dr. Aijun Wang, have already shown they can repair the damage spina bifida causes to the spinal cord, in the womb, in sheep and bulldogs. Last year the CIRM Board voted to fund her research to get the data needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people.
That work is so promising that we decided to profile Dr. Farmer in our 2018 Annual Report.
Here’s excerpts from an interview we conducted with her as part of the Annual Report.
I have been working on this since 2008. We have been thinking about how to help kids with spina bifida walk. It’s not fatal disease but it is a miserable disease.
It’s horrible for parents who think they are about to have a healthy child suddenly be faced with a baby who faces a life long struggle with their health, everything from difficulty or inability to walk to bowel and bladder problems and life-threatening infections.
As a fetal surgeon we used to only focus on fatal diseases because otherwise kids would die. But as we made progress in the field, we had the opportunity to help others who didn’t have a fatal condition, in ways we couldn’t have done in the past.
I’ve always been fascinated by the placenta, it has lots of protective properties. So, we asked the question if we were able to sample fetal cells from the placenta, could we augment those cells, and use them to tissue engineer spinal injuries, in the womb, to improve the outcome for kids with spina bifida?
Dr. Aijun Wang and I have been working on this project for the last decade. Ten years of work has taken us to this point where we are now ready to move this to the next level.
It’s amazing to me how long this process takes and that’s why we are so grateful to CIRM because this is a rare disease and finding funding for those is hard. A lot of people are scared about funding fetal surgery and CIRM has been a perfect partner in helping bring this approach, blending stem cell therapy and tissue engineering, together.
If this therapy is successful it will have a huge economic impact on California, and on the rest of the world. Because spina bifida is a lifelong condition involving many operations, many stays in the hospital, in some cases lifelong use of a wheelchair. This has a huge financial burden on the family. And because this doesn’t just affect the child but the whole family, it has a huge psychological burden on families. It affects them in so many ways; parents having to miss work or take time off work to care for their child, other children in the family feeling neglected because their brother or sister needs so much attention.
In the MOMS Trial (a study that looked at prenatal – before birth – and postnatal – after birth – surgery to repair a defect in the spinal cord and showed that prenatal surgery had strong, long-term benefits and some risks) we showed that we could operate on the fetus before birth and help them. The fact that there was any improvement – doubling the number of kids who could walk from 20 to 40% showed this spinal cord injury is not a permanent situation and also showed there was some plasticity in the spinal cord, some potential for improvement. And so, the next question was can we do more. And that’s why we are trying this.
It’s pretty amazing. We are pretty excited.
The thing that makes surgeon-scientists feel so passionate is that we don’t just ask the fundamental questions, we ask questions in order to cure a problem in patients. I grew up in an environment where people were always asking “how can we do it better, how can we improve?”
There were many times of frustration, many times when cell types we explored and worked with didn’t work. But it’s the patients, seeing them, that keeps me motivated to do the science, to keep persevering. That’s the beauty of being a clinician-scientist. We can ask questions in a different way and look at data in a different way because we are driven by patient outcomes. So, whenever we get stuck in the rabbit hole of theoretical problems, we look to the patients for inspiration to keep going.
I am very cognizant of stirring up false hope, knowing that what occurs in animal models doesn’t always translate into humans. But we are optimistic, and I am anxious to get going.