California’s Stem Cell Agency Accelerates Treatments to Patients

The following article is an Op Ed that appeared in today’s print version of the San Francisco Chronicle

SanFranChronicle_Web

Biotechnology was born in California in the 1970s based on the discovery out of one of its universities and California is responsible for an industry that has impacted the lives of billions of people worldwide. In 2004, the voters of California approved Proposition 71, creating the California Institute for Regenerative Medicine and setting the state on the path to becoming a global leader in stem cell research. Today the therapies resulting from the institute’s work are not just changing lives, they are already saving lives.

Lives like Evie Vaccaro, who is alive today because of a treatment CIRM is funding. Vaccaro was born with SCID, also known as “bubble baby disease,” an immune disorder that often kills babies in their first two years. Vaccaro and dozens of other babies were given stem cell treatments thanks to the institute. All are showing improvement; some are now several years past treatment and considered cured.

An accident left Jake Javier from Danville paralyzed from the chest down on the eve of his high school graduation. Javier was treated in a CIRM-funded clinical trial. Today he has regained the use of his arms and hands, is driving a car and is a sophomore at Cal Poly San Luis Obispo. Five other patients treated at the same time as Javier have all experienced improvements meaning that instead of needing round-the-clock care, they can lead independent lives.

A study by the Tufts Center for the Study of Drug Development estimated it takes at least 10 years and $2.6 billion to develop one successful drug. In 14 years, and with just $3 billion, CIRM has funded 1,000 different projects, enrolled 900 patients, and supported 49 different clinical trials targeting diseases such as cancer, kidney failure and leukemia. Four of these programs have received an expedited designation by the U.S. Food and Drug Administration, meaning they could get faster approval to help more patients

We have created a network of world class medical clinics that have expertise in delivering treatments to patients. The CIRM Alpha Clinics offer treatments based on solid science, unlike the unlicensed clinics sprouting up around California that peddle unproven and potentially harmful therapies that cost patients thousands of dollars.

CIRM has:

  • Supported the creation of 12 stem-cell research facilities in California
  • Attracted hundreds of top-tier researchers to California
  • Trained a new generation of stem-cell scientists
  • Brought clinical trials to California — for example, one targeting ALS or Lou Gehrig’s disease
  • Deployed rigorous scientific standards and support so our programs have a “seal of approval” to attract $2.7 billion in additional investments from industry and other sources.

We recently have partnered with the National Institutes of Health to break down barriers and speed up the approval process to bring curative treatments to patients with Sickle Cell Disease.

Have we achieved all we wanted to? Of course not. The first decade of CIRM’s life was laying the groundwork, developing the knowledge and expertise and refining processes so that we can truly accelerate progress. As a leader in this burgeoning field of regenerative medicine, CIRM needs to continue its mission of accelerating stem-cell treatments to patients with unmet medical needs.

Dr. Maria T. Millan is President and CEO and Jonathan Thomas, JD, PhD, is the Board Chairman of the California Institute of Regenerative Medicine. 

 

 

Stem Cell Agency’s supporting role in advancing research for rare diseases

Orchard

The recent agreement transferring GSK’s rare disease gene therapies to Orchard Therapeutics was good news for both companies and for the patients who are hoping this research could lead to new treatments, even cures, for some rare diseases. It was also good news for CIRM, which played a key role in helping Orchard grow to the point where this deal was possible.

In a news releaseMaria Millan, CIRM’s President & CEO, said:

“At CIRM, our value proposition is centered around our ability to advance the field of regenerative medicine in many different ways. Our funding and partnership has enabled the smooth transfer of Dr. Kohn’s technology from the academic to the industry setting while conducting this important pivotal clinical trial. With our help, Orchard was able to attract more outside investment and now it is able to grow its pipeline utilizing this platform gene therapy approach.”

Under the deal, GSK not only transfers its rare disease gene therapy portfolio to Orchard, it also becomes a shareholder in the company with a 19.9 percent equity stake. GSK is also eligible to receive royalties and commercial milestone payments. This agreement is both a recognition of Orchard’s expertise in this area, and the financial potential of developing treatments for rare conditions.

Dr. Millan says it’s further proof that the agency’s impact on the field of regenerative medicine extends far beyond the funding it offers companies like Orchard.

“Accelerating stem cell therapies to patients with unmet medical needs involves a lot more than just funding research; it involves supporting the research at every stage and creating partnerships to help it fulfill its potential. We invest when others are not ready to take a chance on a promising but early stage project. That early support not only helps the scientists get the data they need to show their work has potential, but it also takes some of the risk out of investments by venture capitalists or larger pharmaceutical companies.”

CIRM’s early support helped UCLA’s Don Kohn, MD, develop a stem cell therapy for severe combined immunodeficiency (SCID). This therapy is now Orchard’s lead program in ADA-SCID, OTL-101.

Sohel Talib, CIRM’s Associate Director Therapeutics and Industry Alliance, says this approach has transformed the lives of dozens of children born with this usually fatal immune disorder.

“This gene correction approach for severe combined immunodeficiency (SCID) has already transformed the lives of dozens of children treated in early trials and CIRM is pleased to be a partner on the confirmatory trial for this transformative treatment for patients born with this fatal immune disorder.”

Dr. Donald B. Kohn UCLA MIMG BSCRC Faculty 180118Dr. Kohn, now a member of Orchard’s scientific advisory board, said:

“CIRM funding has been essential to the overall success of my work, supporting me in navigating the complex regulatory steps of drug development, including interactions with FDA and toxicology studies that enhanced and helped drive the ADA-SCID clinical trial.”

CIRM funding has allowed Orchard Therapeutics to expand its technical operations footprint in California, which now includes facilities in Foster City and Menlo Park, bringing new jobs and generating taxes for the state and local community.

Mark Rothera, Orchard’s President and CEO, commented:

“The partnership with CIRM has been an important catalyst in the continued growth of Orchard Therapeutics as a leading company transforming the lives of patients with rare diseases through innovative gene therapies. The funding and advice from CIRM allowed Orchard to accelerate the development of OTL-101 and to build a manufacturing platform to support our development pipeline which includes 5 clinical and additional preclinical programs for potentially transformative gene therapies”.

Since CIRM was created by the voters of California the Agency has been able to use its support for research to leverage an additional $1.9 billion in funds for California. That money comes in the form of co-funding from companies to support their own projects, partnerships between outside investors or industry groups with CIRM-funded companies to help advance research, and additional funding that companies are able to attract to a project because of CIRM funding.

The Story of a South African Bubble Boy and a Gene Therapy That Gave Him His Life Back

Ayaan Isaacs, health24

Ayaan Isaacs was born in South Africa on March 4th, 2016 as a seemingly healthy baby. But only a few days in to life, he contracted a life-threatening liver infection. He thankfully survived, only to have the doctors discover a few weeks later that he had something much more troubling – a rare disease that left him without a functioning immune system.

Ayaan was diagnosed with X-linked severe combined immunodeficiency (SCID), which is often referred to as ‘bubble baby’ disease because patients are extremely susceptible to infection and must live in sterile environments. SCID patients can be cured with a blood stem cell transplant if they have a genetically matched donor. Unfortunately for Ayaan, only a partially matched donor was available, which doesn’t guarantee a positive outcome.

Ayaan’s parents were desperate for an alternative treatment to save Ayaan’s life. It was at this point that they learned about a clinical trial at St. Jude Children’s Research hospital in Memphis, Tennessee. The trial is treating SCID patients with a stem cell gene therapy that aims to give them a new functioning immune system. The therapy involves extracting the patient’s blood-forming stem cells and genetically correcting the mutation that causes SCID. The corrected blood stem cells are then transplanted back into the patient where they rebuild a healthy immune system.

Ayaan was able to enroll in the trial, and he was the first child in Africa to receive this life-saving gene therapy treatment. Ayaan’s journey with bubble boy disease was featured by South Africa’s health24 earlier this year. In the article, his mom Shamma Sheik talked about the hope that this gene therapy treatment brought to their family.

“No child should have to die just because they are unable to find a donor. Gene therapy offered Ayaan a chance at life that he ordinarily would not have had. I was fortunate to have found an alternative therapy that is working and already showing remarkable results. We are mindful that this is still an experimental treatment and there are complications that can arise; however, I am very optimistic that he will return to South Africa with a functioning immune system.”

Carte Blanche, an investigative journalism program in South Africa, did a feature video of Ayaan in February. Although the video is no longer available on their website, it did reveal that four months after Ayaan’s treatment, his condition started to improve suggesting that the treatment was potentially working.

We’ve written previously about another young boy named Ronnie who was diagnosed with X-linked SCID days after he was born. Ronnie also received the St. Jude stem cell gene therapy in a CIRM-funded clinical trial at the UCSF Benioff Children’s Hospital. Ronnie was treated when he was six months old and just celebrated his first birthday as a healthy, vibrant kid thanks to this trial. You can hear more about Ronnie’s moving story from his dad, Pawash Priyank, in the video below.

Our hope is that powerful stories like Ayaan’s and Ronnie’s will raise awareness about SCID and the promising potential of stem cell gene therapies to cure patients of this life-threatening immune disease.

Ronnie and his parents celebrating his 1st birthday. (Photo courtesy of Pawash Priyank)


Related Links:

Breaking the isolation of rare diseases

Rare disease day

Rare Disease Day in Sacramento, California

How can something that affects 30 million Americans, one in ten people in the US, be called rare? But that’s the case with people who have a rare disease. There are around 7,000 different diseases that are categorized as rare because they affect fewer than 200,000 people. Less than five percent of these diseases have a treatment.

That’s why last Wednesday, in cities across the US, members of the rare disease community gathered to call for more support, more research, and more help for families battling these diseases. Their slogan tells their story, ‘Alone we are rare; Together we are strong.’

At the Rare Disease Day rally in Sacramento, California, I met Kerry Rivas. Kerry’s son Donovan has a life-threatening condition called Shprintzen-Goldberg Syndrome. Talk about rare. There are only 70 documented cases of the syndrome worldwide. Just getting a diagnosis for Donovan took years.

DonovanDonovan suffers from a lot of problems but the most serious affect his heart, lungs and spinal cord. Getting him the care he needs is time consuming and expensive and has forced Kerry and her family to make some big sacrifices. Even so they work hard to try and see that Donovan is able to lead as normal a life as is possible.

While the disease Kerry’s son has is rarer than most, everyone at Rare Disease Day had a similar story, and an equal commitment to doing all they can to be an effective advocate. And their voices are being heard.

To honor the occasion the US Food and Drug Administration (FDA) announced it was partnering with the National Organization of Rare Diseases (NORD) to hold listening sessions involving patients and FDA medical reviewers.

In a news release Peter L. Saltonstall, President and CEO of NORD, said:

“These listening sessions will provide FDA review division staff with better insight into what is important to patients in managing their diseases and improving their quality of life. It is important for FDA to understand, from the patient perspective, disease burden, management of symptoms, daily impact on quality of life, and patients’ risk tolerance. Patients and caregivers bring a pragmatic, realistic perspective about what they are willing to deal with in terms of potential risks and benefits for new therapies.”

FDA Commissioner Dr. Scott Gottlieb said his agency is committed to doing everything possible to help the rare disease community:

“Despite our successes, there are still no treatments for the vast proportion of rare diseases or conditions. FDA is committed to do what we can to stimulate the development of more products by improving the consistency and efficiency of our reviews, streamlining our processes and supporting rare disease research.”

At CIRM we are also committed to doing all we can to help the cause. Many of the diseases we are currently funding in clinical trials are rare diseases like ALS or Lou Gehrig’s disease, SCID, spinal cord injury and sickle cell disease.

Many pharmaceutical companies are shy about funding research targeting these diseases because the number of patients involved is small, so the chances of recouping their investment or even making a profit is small.

At CIRM we don’t have to worry about those considerations. Our focus is solely on helping those in need. People like Donovan Rivas.

Friday Roundup: A better kind of blood stem cell transplant; Encouraging news from spinal cord injury trial; Finding an “elusive” cell that could help diabetics

Cool Instagram image of the week:

Pancreatic Progenitors

Diabetes Research Institute scientists have confirmed that the unique stem cells reside within large ducts of the human pancreas. Two such ducts (green) surrounded by three islets (white) are shown. [Diabetes Research Institute Foundation]

Chemo- and radiation-free blood stem cell transplant showing promise

Bubble baby disease, also known as severe combined immunodeficiency (SCID), is an inherited disorder that leaves newborns without an effective immune system. Currently, the only approved treatment for SCID is a blood stem cell transplant, in which the patient’s defective immune system cells are eliminated by chemotherapy or radiation to clear out space for cells from a healthy, matched donor. Even though the disease can be fatal, physicians loathe to perform a stem cell transplant on bubble baby patients:

Shizuru“Physicians often choose not to give chemotherapy or radiation to young children with SCID because there are lifelong effects: neurological impairment, growth delays, infertility, risk of cancer, etc.,” says Judith Shizuru, MD, PhD, professor of medicine at Stanford University.

To avoid these complications, Dr. Shizuru is currently running a CIRM-funded clinical trial testing a gentler approach to prepare patients for blood stem cell transplants. She presented promising, preliminary results of the trial on Tuesday at the annual meeting of Stanford’s Center for Definitive and Curative Medicine.

Trial participants are receiving a protein antibody called CD117 before their stem cell transplant. Previous studies in animals showed that this antibody binds to the surface of blood stem cells and blocks the action of a factor which is required for stem cell survival. This property of CD117 provides a means to get rid of blood stem cells without radiation or chemotherapy.

Early results in two participants indicate that, 6 and 9 months after receiving the CD117 blood stem cell transplants, the donor cells have successfully established themselves in the patients and begun making immune cells.

Spinal cord injury trial reports more promising results:

AsteriasRegular readers of our blog will already know about our funding for the clinical trial being run by Asterias Biotherapeutics to treat spinal cord injuries. The latest news from the company is very encouraging, in terms of both the safety and effectiveness of the treatment.

Asterias is transplanting stem cells into patients who have suffered recent injuries that have left them paralyzed from the neck down. It’s hoped the treatment will restore connections at the injury site, allowing patients to regain some movement and feeling in their hands and arms.

This week the company announced that of the 25 patients they have treated there have been no serious side effects. In addition:

  • Magnetic Resonance Imaging (MRI) scans show that in more than 90 percent of the patients the cells appear to show signs of engraftment
  • At least 75 percent of those treated have recovered at least one motor level, and almost 20 percent have recovered two levels

In a news release, Michael Mulroy, Asterias’ President and CEO, said:

“The positive safety profile to date, the evidence supporting engraftment of the cells post-implantation, and the improvements we are seeing in upper extremity motor function highlight the promising findings coming from this Phase 1/2a clinical trial, which will guide us as we work to design future studies.”

There you are! Finding the “elusive” human pancreatic progenitor cells – the story behind our cool Instagram image of the week.

Don’t you hate it when you lose something and can’t find it? Well imagine the frustration of scientists who were looking for a group of cells they were sure existed but for decades they couldn’t locate them. Particularly as those cells might help in developing new treatments for diabetes.

Diabetes-Research-Institute_University-of-Miami-Miller-School-of-MedicineWell, rest easy, because scientists at the Diabetes Research Institute at the University of Miami finally found them.

In a study, published in Genetic Engineering and Biotechnology News, the researchers show how they found these progenitor cells in the human pancreas, tucked away in the glands and ducts of the organ.

In type 1 diabetes, the insulin-producing cells in the pancreas are destroyed. Finding these progenitor cells, which have the ability to turn into the kinds of cells that produce insulin, means researchers could develop new ways to regenerate the pancreas’ ability to function normally.

That’s a long way away but this discovery could be an important first step along that path.

Using the AIDS virus to help children battling a deadly immune disorder

Ronnie Kashyap, patient in SCID clinical trial: Photo Pawash Priyank

More than 35 million people around the world have been killed by HIV, the virus that causes AIDS. So, it’s hard to think that the same approach the virus uses to infect cells could also be used to help children battling a deadly immune system disorder. But that’s precisely what researchers at UC San Francisco and St. Jude Children’s Research Hospital are doing.

The disease the researchers are tackling is a form of severe combined immunodeficiency (SCID). It’s also known as ‘bubble baby’ disease because children are born without a functioning immune system and in the past were protected from germs within the sterile environment of a plastic bubble. Children with this disease often die of infections, even from a common cold, in the first two years of life.

The therapy involves taking the patient’s own blood stem cells from their bone marrow, then genetically modifying them to correct the genetic mutation that causes SCID. The patient is then given low-doses of chemotherapy to create space in their bone marrow for the news cells. The gene-corrected stem cells are then transplanted back into the infant, creating a new blood supply and a repaired immune system.

Unique delivery system

The novel part of this approach is that the researchers are using an inactivated form of HIV as a means to deliver the correct gene into the patient’s cells. It’s well known that HIV is perfectly equipped to infiltrate cells, so by taking an inactivated form – meaning it cannot infect the individual with HIV – they are able to use that infiltrating ability for good.

The results were announced at the American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta.

The researchers say seven infants treated and followed for up to 12 months, have all produced the three major immune system cell types affected by SCID. In a news release, lead author Ewelina Mamcarz, said all the babies appear to be doing very well:

“It is very exciting that we observed restoration of all three very important cell types in the immune system. This is something that’s never been done in infants and a huge advantage over prior trials. The initial results also suggest our approach is fundamentally safer than previous attempts.”

One of the infants taking part in the trial is Ronnie Kashyap. We posted a video of his story on our blog, The Stem Cellar.

If the stem cell-gene therapy combination continues to show it is both safe and effective it would be a big step forward in treating SCID. Right now, the best treatment is a bone marrow transplant, but only around 20 percent of infants with SCID have a sibling or other donor who is a good match. The other 80 percent have to rely on a less well-matched bone marrow transplant – usually from a parent – that can still leave the child prone to life-threatening infections or potentially fatal complications such as graft-versus-host disease.

CIRM is funding two other clinical trials targeting SCID. You can read about them here and here.

Progress to a Cure for Bubble Baby Disease

Welcome back to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of exciting stem cell stories about advances towards stem cell-based cures for serious diseases. Today we’re featuring stories about the progress of CIRM-funded clinical trials for the treatment of a devastating, usually fatal, primary immune disease that strikes newborn babies.

evangelina in a bubble

Evie, a former “bubble baby” enjoying life by playing inside a giant plastic bubble

‘Bubble baby disease’ will one day be a thing of the past. That’s a bold statement, but I say it with confidence because of the recent advancements in stem cell gene therapies that are curing infants of this life-threatening immune disease.

The scientific name for ‘bubble baby disease’ is severe combined immunodeficiency (SCID). It prevents the proper development of important immune cells called B and T cells, leaving newborns without a functioning immune system. Because of this, SCID babies are highly susceptible to deadly infections, and without treatment, most of these babies do not live past their first year. Even a simple cold virus can be fatal.

Scientists are working hard to develop stem cell-based gene therapies that will cure SCID babies in their first months of life before they succumb to infections. The technology involves taking blood stem cells from a patient’s bone marrow and genetically correcting the SCID mutation in the DNA of these cells. The corrected stem cells are then transplanted back into the patient where they can grow and regenerate a healthy immune system. Early-stage clinical trials testing these stem cell gene therapies are showing very encouraging results. We’ll share a few of these stories with you below.

CIRM-funded trials for SCID

CIRM is funding three clinical trials, one from UCLA, one at Stanford and one from UCSF & St. Jude Children’s Research Hospital, that are treating different forms of SCID using stem cell gene therapies.

Adenosine Deaminase-Deficient SCID

The first trial is targeting a form of the disease called adenosine deaminase-deficient SCID or ADA-SCID. Patients with ADA-SCID are unable to make an enzyme that is essential for the function of infection-fighting immune cells called lymphocytes. Without working lymphocytes, infants eventually are diagnosed with SCID at 6 months. ADA-SCID occurs in approximately 1 in 200,000 newborns and makes up 15% of SCID cases.

CIRM is funding a Phase 2 trial for ADA-SCID that is testing a stem cell gene therapy called OTL-101 developed by Dr. Don Kohn and his team at UCLA and a company called Orchard Therapeutics. 10 patients were treated in the trial, and amazingly, nine of these patients were cured of their disease. The 10th patient was a teenager who received the treatment knowing that it might not work as it does in infants. You can read more about this trial in our blog from earlier this year.

In a recent news release, Orchard Therapeutics announced that the US Food and Drug Administration (FDA) has awarded Rare Pediatric Disease Designation to OTL-101, meaning that the company will qualify for priority review for drug approval by the FDA. You can read more about what this designation means in this blog.

X-linked SCID

The second SCID trial CIRM is funding is treating patients with X-linked SCID. These patients have a genetic mutation on a gene located on the X-chromosome that causes the disease. Because of this, the disease usually affects boys who have inherited the mutation from their mothers. X-linked SCID is the most common form of SCID and appears in 1 in 60,000 infants.

UCSF and St. Jude Children’s Research Hospital are conducting a Phase 1/2 trial for X-linked SCID. The trial, led by Dr. Brian Sorrentino, is transplanting a patient’s own genetically modified blood stem cells back into their body to give them a healthy new immune system. Patients do receive chemotherapy to remove their diseased bone marrow, but doctors at UCSF are optimizing low doses of chemotherapy for each patient to minimize any long-term effects. According to a UCSF news release, the trial is planning to treat 15 children over the next five years. Some of these patients have already been treated and we will likely get updates on their progress next year.

CIRM is also funding a third clinical trial out of Stanford University that is hoping to make bone marrow transplants safer for X-linked SCID patients. The team, led by Dr. Judy Shizuru, is developing a therapy that will remove unhealthy blood stem cells from SCID patients to improve the survival and engraftment of healthy bone marrow transplants. You can read more about this trial on our clinical trials page.

SCID Patients Cured by Stem Cells

These clinical trial results are definitely exciting, but what is more exciting are the patient stories that we have to share. We’ve spoken with a few of the families whose children participated in the UCLA and UCSF/St. Jude trials, and we asked them to share their stories so that other families can know that there is hope. They are truly inspiring stories of heartbreak and joyful celebration.

Evie is a now six-year-old girl who was diagnosed with ADA-SCID when she was just a few months old. She is now cured thanks to Don Kohn and the UCLA trial. Her mom gave a very moving presentation about Evie’s journey at the CIRM Bridges Trainee Annual Meeting this past July.  You can watch the 20-minute talk below:

Ronnie’s story

Ronnie SCID kid

Ronnie: Photo courtesy Pawash Priyank

Ronnie, who is still less than a year old, was diagnosed with X-linked SCID just days after he was born. Luckily doctors told his parents about the UCSF/St. Jude trial and Ronnie was given the life-saving stem cell gene therapy before he was six months old. Now Ronnie is building a healthy immune system and is doing well back at home with his family. Ronnie’s dad Pawash shared his families moving story at our September Board meeting and you can watch it here.

Our mission at CIRM is to accelerate stem cell treatments to patients with unmet medical needs. We hope that by funding promising clinical trials like the ones mentioned in this blog, that one day soon there will be approved stem cell therapies for patients with SCID and other life-threatening diseases.

From trauma to treatment: a Patient Advocate’s journey from helping her son battle a deadly disease to helping others do the same

Everett SCID 1

For every clinical trial CIRM funds we create a Clinical Advisory Panel or CAP. The purpose of the CAP is to make recommendations and provide guidance and advice to both CIRM and the Project Team running the trial. It’s part of our commitment to doing everything we can to help make the trial a success and get therapies to the people who need them most, the patients.

Each CAP consists of three to five members, including a Patient Advocate, an external scientific expert, and a CIRM Science Officer.

Having a Patient Advocate on a CAP fills a critical need for insight from the patient’s perspective, helping shape the trial, making sure that it is being carried out in a way that has the patient at the center. A trial designed around the patient, and with the needs of the patient in mind, is much more likely to be successful in recruiting and retaining the patients it needs to see if the therapy works.

One of the clinical trials we are currently funding is focused on severe combined immunodeficiency disease, or SCID. It’s also known as “bubble baby” disease because children with SCID are born without a functioning immune system, so even a simple virus or infection can prove fatal. In the past some of these children were kept inside sterile plastic bubbles to protect them, hence the name “bubble baby.”

Everett SCID family

Anne Klein is the Patient Advocate on the CAP for the CIRM-funded SCID trial at UCSF and St. Jude Children’s Research Hospital. Her son Everett was born with SCID and participated in this clinical trial. We asked Anne to talk about her experience as the mother of a child with SCID, and being part of the research that could help cure children like Everett.

“When Everett was born his disease was detected through a newborn screening test. We found out he had SCID on a Wednesday, and by  Thursday we were at UCSF (University of California, San Francisco). It was very sudden and quite traumatic for the family, especially Alden (her older son). I was abruptly taken from Alden, who was just two and a half years old at the time, for two months. My husband, Brian Schmitt, had to immediately drop many responsibilities required to effectively run his small business. We weren’t prepared. It was really hard.”

(Everett had his first blood stem cell transplant when he was 7 weeks old – his mother Anne was the donor. It helped partially restore his immune system but it also resulted in some rare, severe complications as a result of his mother’s donor cells attacking his body. So when, three years later, the opportunity to get a stem cell therapy came along Anne and her husband, Brian, decided to say yes. After some initial problems following the transplant, Everett seems to be doing well and his immune system is the strongest it has ever been.)

“It’s been four years, a lot of ups and downs and a lot of trauma. But it feels like we have turned a corner. Everett can go outside now and play, and we’re hanging out more socially because we no longer have to be so concerned about him being exposed to germs or viruses.

His doctor has approved him to go to daycare, which is amazing. So, Everett is emerging into the “normal” world for the first time. It’s nerve wracking for us, but it’s also a relief.”

Everett SCID in hospital

How Anne came to be on the CAP

“Dr. Cowan from UCSF and Dr. Malech from the NIH (National Institutes of Health) reached out to me and asked me about it a few months ago. I immediately wanted to be part of the group because, obviously, it is something I am passionate about. Knowing families with SCID and what they go through, and what we went through, I will do everything I can to help make this treatment more available to as many people as need it.

I can provide insight on what it’s like to have SCID, from the patient perspective; the traumas you go through. I can help the doctors and researchers understand how the medical community can be perceived by SCID families, how appreciative we are of the medical staff and the amazing things they do for us.

I am connected to other families, both within and outside of the US, affected by this disease so I can help get the word out about this treatment and answer questions for families who want to know. It’s incredibly therapeutic to be part of this wider community, to be able to help others who have been diagnosed more recently.”

The CAP Team

“They were incredibly nice and when I did speak they were very supportive and seemed genuinely interested in getting feedback from me. I felt very comfortable. I felt they were appreciative of the patient perspective.

I think when you are a research scientist in the lab, it’s easy to miss the perspective of someone who is actually experiencing the disease you are trying to fix.

At the NIH, where Everett had his therapy, the stem cell lab people work so hard to process the gene corrected cells and get them to the patient in time. I looked through the window into the hall when Everett was getting his therapy and the lab staff were outside, in their lab coats, watching him getting his new cells infused. They wanted to see the recipient of the life-saving treatment that they prepared.

It is amazing to see the process that the doctors go through to get treatments approved. I like being on the CAP and learning about the science behind it and I think if this is successful in treating others, then that would be the best reward.”

The future:

“We still have to fly back to the NIH, in Bethesda, MD, every three months for checkups. We’ll be doing this for 15 years, until Everett is 18. It will be less frequent as Everett gets older but this kind of treatment is so new that it’s still important to do this kind of follow-up. In between those trips we go to UCSF every month, and Kaiser every 1-3 weeks, sometimes more.

I think the idea of being “cured”, when you have been through this, is a difficult thing to think about. It’s not a word I use lightly as it’s a very weighted term. We have been given the “all clear” before, only to be dealt setbacks later. Once he’s in school and has successfully conquered some normal childhood illnesses, both Brian and I will be able to relax more.

One of Everett’s many doctors once shared with me that, in the past, he sometimes had to tell parents of very sick children with SCID that there was nothing else they could do to help them. So now to have a potential treatment like this, he was so excited about a stem cell therapy showing such promise.

One thing we think about Everett and Alden, is that they are both so young and have been through so much already. I’m hoping that they can forget all this and have a chance to grow up and lead a normal life.”

Stem cell stories that caught our eye: bubble baby therapy a go in UK, in-utero stem cell trial and novel heart disease target

There were lots of CIRM mentions in the news this week. Here are two brief recaps written by Karen Ring to get you up to speed. A third story by Todd Dubnicoff summarizes an promising finding related to heart disease by researchers in Singapore.  

CIRM-funded “bubble baby” disease therapy gets special designation by UK.
Orchard Therapeutics, a company based in the UK and the US, is developing a stem cell-based gene therapy called OTL-101 to treat a primary immune disease called adenosine-deaminase deficient severe combined immunodeficiency (ADA-SCID), also known as “bubble baby disease”. CIRM is funding a Phase 1/2 clinical trial led by Don Kohn of UCLA in collaboration with Orchard and the University College in London.

In July, the US Food and Drug Administration (FDA) awarded OTL-101 Rare Pediatric Disease Designation (read more about it here), which makes the therapy eligible for priority review by the FDA, and could give it a faster route to being made more widely available to children in need.

On Tuesday, Orchard announced further good news that OTL-101 received “Promising Innovative Medicine Designation” by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA). In a news release, the company explained how this designation bodes well for advancing OTL-101 from clinical trials into patients,

“The designation as Promising Innovative Medicine is the first step of a two-step process under which OTL-101 can benefit from the Early Access to Medicine Scheme (“EAMS”). Nicolas Koebel, Senior Vice President for Business Operations at Orchard, added: “With this PIM designation we can potentially make OTL-101 available to UK patients sooner under the Early Access to Medicine Scheme”.

CIRM funded UCSF clinical trial mentioned in SF Business Times
Ron Leuty, reporter at the San Francisco Business Times, published an article about a CIRM-funded trial out of UCSF that is targeting a rare genetic blood disease called alpha thalassemia major, describing it as, “The world’s first in-utero blood stem cell transplant, soon to be performed at the University of California, San Francisco, could point the way toward pre-birth cures for a range of blood diseases, such as sickle cell disease.”

Alpha Thalassemia affects the ability of red blood cells to carry oxygen because of a reduction in a protein called hemoglobin. The UCSF trial, spearheaded by UCSF Pediatric surgeon Dr. Tippi MacKenzie, is hoping to use stem cells from the mother to treat babies in the womb to give them a better chance at surviving after birth.

In an interview with Leuty, Tippi explained,

“Our goal is to put in enough cells so the baby won’t need another transplant. But even if we fall short, if we can just establish 1 percent maternal cells circulating in the child, it will establish tolerance and then they can get the booster transplant.”

She also emphasized the key role that CIRM funded played in the development and launch of this clinical trial.

“CIRM is about more than funding for studies, MacKenzie said. Agency staff has provided advice about how to translate animal studies into work in humans, she said, as well as hiring an FDA consultant, writing an investigational new drug application and setting up a clinical protocol.”

“I’m a clinician, but running a clinical trial is different,” MacKenzie said. “CIRM’s been incredibly helpful in helping me navigate that.”

Heart, heal thyself: the story of Singheart
When you cut your finger or scrape a knee, a scab forms, allowing the skin underneath to regenerate and repair itself. The heart is not so lucky – it has very limited self-healing abilities. Instead, heart muscle cells damaged after a heart attack form scar tissue, making each heart beat less efficient. This condition can lead to chronic heart disease, the number one killer of both men and women in the US.

A mouse heart cell with 2 nuclei (blue) and Singheart RNA labelled by red fluorescent dyes.
Credit: A*STAR’s Genome Institute of Singapore

Research has shown that newborn mice retain the ability to completely regenerate and repair injuries to the heart because their heart muscle cells, or cardiomyocytes, are still able to divide and replenish damaged cells. But by adulthood, the mouse cardiomyocytes lose the ability to stimulate the necessary cell division processes. A research team in Singapore wondered what was preventing cardiomyocytes cell division in adult mice and if there was some way to lift that block.

This week in Nature Communications, they describe the identification of a molecule they call Singheart that may be the answer to their questions. Using tools that allow the analysis of gene activity in single cells revealed that a rare population of diseased cardiomyocytes are able to crank up genes related to cell division. And further analysis showed Singheart, a specialized genetic molecule called a long non-coding RNA, played a role in blocking this cell division gene.

As lead author Dr. Roger Foo, a principal investigator at Genome Institute of Singapore (GIS) and the National University Health System (NUHS), explained in a press release, these findings may lead to new self-healing strategies for heart disease,

“There has always been a suspicion that the heart holds the key to its own healing, regenerative and repair capability. But that ability seems to become blocked as soon as the heart is past its developmental stage. Our findings point to this potential block that when lifted, may allow the heart to heal itself.”

CIRM-funded life-saving stem cell therapy gets nod of approval from FDA

Cured_AR_2016_coverIf you have read our 2016 Annual Report (and if you haven’t you should, it’s brilliant) or just seen the cover you’ll know that it features very prominently a young girl named Evie Padilla Vaccaro.

Evie was born with Severe Combined Immunodeficiency or SCID – also known as “bubble baby disease”; we’ve written about it here. SCID is a rare but deadly immune disorder which leaves children unable to fight off simple infections. Many children with SCID die in the first few years of life.

Fortunately for Evie and her family, Dr. Don Kohn and his team at UCLA, working with a UK-based company called Orchard Therapeutics Ltd., have developed a treatment called OTL-101. This involves taking the patient’s own blood stem cells, genetically modifying them to correct the SCID mutation, and then returning the cells to the patient. Those modified cells create a new blood supply, and repair the child’s immune system.

Evie was treated with OTL-101 when she was a few months old. She is cured. And she isn’t the only one. To date more than 40 children have been treated with this method. All have survived and are doing well.

Orchard Therapeutics

 FDA acknowledgement

Because of that success the US Food and Drug Administration (FDA) has granted OTL-101 Rare Pediatric Disease Designation. This status is given to a treatment that targets a serious or life-threatening disease that affects less than 200,000 people, most of whom are under 18 years of age.

The importance of the Rare Pediatric Disease Designation is that it gives the company certain incentives for the therapy’s development, including priority review by the FDA. That means if it continues to show it is safe and effective it may have a faster route to being made more widely available to children in need.

In a news release Anne Dupraz, PhD, Orchard’s Chief Regulatory Officer, welcomed the decision:

“Together with Orphan Drug and Breakthrough Therapy Designations, this additional designation is another important development step for the OTL-101 clinical program. It reflects the potential of this gene therapy treatment to address the significant unmet medical need of children with ADA-SCID and eligibility for a Pediatric Disease Priority Review voucher at time of approval.”

Creating a trend

This is the second time in less than two weeks that a CIRM-funded therapy has been awarded Rare Pediatric Disease designation. Earlier this month Capricor Therapeutics was given that status for its treatment for Duchenne Muscular Dystrophy.

Two other CIRM-funded clinical trials – Humacyte and jCyte – have been given Regenerative Medicine Advanced Therapy Designation (RMAT) by the FDA. This makes them eligible for earlier and faster interactions with the FDA, and also means they may be able to apply for priority review and faster approval.

All these are encouraging signs for a couple of reasons. It suggests that the therapies are showing real promise in clinical trials. And it shows that the FDA is taking steps to encourage those therapies to advance as quickly – and safely of course – as possible.

Credit where credit is due

In the past we have been actively critical of the FDA’s sluggish pace in moving stem cell therapies out of the lab and into clinical trials where they can be tested in people. So when the FDA does show signs of changing the way it works it’s appropriate that that we are actively supportive.

Getting these designations is, of course, no guarantee the therapies will ultimately prove to be successful. But if they are, creating faster pathways means they can get to patients, the people who really need them, at a much faster pace.