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.

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The Alpha Stem Cell Clinics: Innovation for Breakthrough Stem Cell Treatments

During this third week of the Month of CIRM, we are focusing on CIRM’s Infrastructure programs which are all focused on helping to accelerate stem cell treatments to patients with unmet medical needs.

So here is the question of the day: What is the world’s largest network of medical centers dedicated to providing stem cell treatments to patients?

The answer is the CIRM Alpha Stem Cell Clinics Network.

The CIRM Alpha Stem Cell Clinics Network consists of leading medical institutions throughout California.

The ASCC Network consists of six leading medical centers throughout California. In 2015, the Network was launched in southern California at the City of Hope, UC Irvine, UC Los Angeles, and UC San Diego. In September 2017, CIRM awarded funding to UC Davis and UC San Francisco to enable the Network to better serve patients throughout the state. Forty stem cell clinical trials have been conducted within the Network with hundreds of patients being treat for a variety of conditions, including:

  • Cancers of the blood, brain, lung and other sites
  • Organ diseases of the heart and kidney
  • Pediatric diseases
  • Traumatic injury to the brain and spine

A complete list of clinical trials may be found on our website.

The Alpha Clinics at UC Los Angeles and San Francisco are working collaboratively on breakthrough treatments for serious childhood diseases. This video highlights a CIRM-funded clinical trial at the UCLA Alpha Clinic that is designed to restore the immune system of patients with life-threatening immune deficiencies. A similar breakthrough treatment is also being used at the UCLA Alpha Clinic to treat sickle cell disease. A video describing this treatment is below.

Why do we need a specialized Network for stem cell clinical trials?

Stem cell treatments are unique in many ways. First, they consist of cells or cell products that frequently require specialized processing. For example, the breakthrough treatments for children, described above, requires the bone marrow to be genetically modified to correct defects. This “gene therapy” is performed in the Alpha Clinic laboratories, which are specifically designed to implement cutting edge gene therapy techniques on the patient’s stem cells.

Many of the cancer clinical trials also take the patient’s own cells and then process them in a laboratory. This processing is designed to enhance the patient’s ability to fight cancer using their own immune cells. Each Alpha Clinic has specialized laboratories to process cells, and the sites at City of Hope and UC Davis have world-class facilities for stem cell manufacturing. The City of Hope and Davis facilities produce high quality therapeutic products for commercial and academic clinical trial sponsors. Because of this ability, the Network has become a prime location internationally for clinical trials requiring processing and manufacturing services.

Another unique feature of the Network is its partnership with CIRM, whose mission is to accelerate stem cell treatments for patients with unmet medical needs. Often, this means developing treatments for rare diseases in which the patient population is comparatively small. For example, there about 40-100 immune deficient children born each year in the United States. We are funding clinical trials to help treat those children. The Network is also treating rare brain and blood cancers.

To find patients that may benefit from these treatments, the Network has developed the capacity to confidentially query over 20 million California patient records. If a good match is found, there is a procedure in place, that is reviewed by an ethics committee, where the patient’s doctor can be notified of the trial and pass that information to the patient. For patients that are interested in learning more, each Alpha Clinic has a Patient Care Coordinator with the job of coordinating the process of educating patients about the trial and assisting them if they choose to participate.

How Can I Learn More?

If you are a patient or a family member and would like to learn more about the CIRM Alpha Clinics, click here. There is contact information for each clinic so you can learn more about specific trials, or you can visit our Alpha Clinics Trials page for a complete list of trials ongoing in the Network.

If you are a patient or a trial sponsor interested in learning more about the services offered through our Alpha Clinics Network, visit our website.

Caught our eye: new Americans 4 Cures video, better mini-brains reveal Zika insights and iPSC recipes go head-to-head

How stem cell research gives patients hope (Karen Ring).
You can learn about the latest stem cell research for a given disease in seconds with a quick google search. You’ll find countless publications, news releases and blogs detailing the latest advancements that are bringing scientists and clinicians closer to understanding why diseases happen and how to treat or cure them.

But one thing these forms of communications lack is the personal aspect. A typical science article explains the research behind the study at the beginning and ends with a concluding statement usually saying how the research could one day lead to a treatment for X disease. It’s interesting, but not always the most inspirational way to learn about science when the formula doesn’t change.

However, I’ve started to notice that more and more, institutes and organizations are creating videos that feature the scientists/doctors that are developing these treatments AND the patients that the treatments could one day help. This is an excellent way to communicate with the public! When you watch and listen to a patient talk about their struggles with their disease and how there aren’t effective treatments at the moment, it becomes clear why funding and advancing research is important.

We have a great example of a patient-focused stem cell video to share with you today thanks to our friends at Americans for Cures, a non-profit organization that advocates for stem cell research. They posted a new video this week in honor of Stem Cell Awareness Day featuring patients and patient advocates responding to the question, “What does stem cell research give you hope for?”. Many of these patients and advocates are CIRM Stem Cell Champions that we’ve featured on our website, blog, and YouTube channel.

Americans for Cures is encouraging viewers to take their own stab at answering this important question by sharing a short message (on their website) or recording a video that they will share with the stem cell community. We hope that you are up for the challenge!

Mini-brains help uncover some of Zika’s secrets (Kevin McCormack).
One of the hardest things about trying to understand how a virus like Zika can damage the brain is that it’s hard to see what’s going on inside a living brain. That’s not surprising. It’s not considered polite to do an autopsy of someone’s brain while they are still using it.

Human organoid_800x533

Microscopic image of a mini brain organoid, showing layered neural tissue and different groups of neural stem cells (in blue, red and magenta) giving rise to neurons (green). Image: Novitch laboratory/UCLA

But now researchers at UCLA have come up with a way to mimic human brains, and that is enabling them to better understand how Zika inflicts damage on a developing fetus.

For years researchers have been using stem cells to help create “mini brain organoids”, essentially clusters of some of the cells found in the brain. They were helpful in studying some aspects of brain behavior but limited because they were very small and didn’t reflect the layered complexity of the brain.

In a study, published in the journal Cell Reports, UCLA researchers showed how they developed a new method of creating mini-brain organoids that better reflected a real brain. For example, the organoids had many of the cells found in the human cortex, the part of the brain that controls thought, speech and decision making. They also found that the different cells could communicate with each other, the way they do in a real brain.

They used these organoids to see how the Zika virus attacks the brain, damaging cells during the earliest stages of brain development.

In a news release, Momoko Watanabe, the study’s first author, says these new organoids can open up a whole new way of looking at the brain:

“While our organoids are in no way close to being fully functional human brains, they mimic the human brain structure much more consistently than other models. Other scientists can use our methods to improve brain research because the data will be more accurate and consistent from experiment to experiment and more comparable to the real human brain.”

iPSC recipes go head-to-head: which one is best?
In the ten years since the induced pluripotent stem cell (iPSC) technique was first reported, many different protocols, or recipes, for reprogramming adult cells, like skin, into iPSCs have been developed. These variations bring up the question of which reprogramming recipe is best. This question isn’t the easiest to answer given the many variables that one needs to test. Due to the cost and complexity of the methods, comparisons of iPSCs generated in different labs are often performed. But one analysis found significant lab-to-lab variability which can really muck up the ability to make a fair comparison.

A Stanford University research team, led by Dr. Joseph Wu, sought to eliminate these confounding variables so that any differences found could be attributed specifically to the recipe. So, they tested six different reprogramming methods in the same lab, using cells from the same female donor. And in turn, these cells were compared to a female source of embryonic stem cells, the gold standard of pluripotent stem cells. They reported their findings this week in Nature Biomedical Engineering.

Previous studies had hinted that the reprogramming protocol could affect the ability to fully specialize iPSCs into a particular cell type. But based on their comparisons, the protocol chosen did not have a significant impact on how well iPSCs can be matured. Differences in gene activity are a key way that researchers do side-by-side comparisons of iPSCs and embryonic stem cells. And based on the results in this study, the reprogramming method itself can influence the differences. A gene activity comparison of all the iPSCs with the embryonic stem cells found the polycomb repressive complex – a set of genes that play an important role in embryonic development and are implicated in cancer – had the biggest difference.

In a “Behind the Paper” report to the journal, first author Jared Churko, says that based on these findings, their lab now mostly uses one reprogramming protocol – which uses the Sendai virus to deliver the reprogramming genes to the cells:

“The majority of our hiPSC lines are now generated using Sendai virus. This is due to the ease in generating hiPSCs using this method as well as the little to no chance of transgene integration [a case in which a reprogramming gene inserts into the cells’ DNA which could lead to cancerous growth].”

Still, he adds a caveat that the virus does tend to linger in the cells which suggests that:

“cell source or reprogramming method utilized, each hiPSC line still requires robust characterization prior to them being used for downstream experimentation or clinical use.”

 

CIRM-Funded Clinical Trials Targeting Blood and Immune Disorders

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our blood and immune disorders portfolio, specifically focusing on sickle cell disease, HIV/AIDS, severe combined immunodeficiency (SCID, also known as bubble baby disease) and rare disease called chronic granulomatous disease (CGD).

CIRM has funded a total of eight trials targeting these disease areas, all of which are currently active. Check out the infographic below for a list of those trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

CIRM-Funded Clinical Trials Targeting Cancers

Welcome to the Month of CIRM!

As we mentioned in last Thursday’s blog, during the month of October we’ll be looking back at what CIRM has done since the agency was created by the people of California back in 2004. To start things off, we’ll be focusing on CIRM-funded clinical trials this week. Supporting clinical trials through our funding and partnership is a critical cornerstone to achieving our mission: to accelerate stem cell treatments to patients with unmet medical needs.

Over the next four days, we will post infographics that summarize CIRM-funded trials focused on therapies for cancer, neurologic disorders, heart and metabolic disease, and blood disorders. Today, we review the nine CIRM-funded clinical trial projects that target cancer. The therapeutic strategies are as varied as the types of cancers the researchers are trying to eradicate. But the common element is developing cutting edge methods to outsmart the cancer cell’s ability to evade standard treatment.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

UCLA scientists begin a journey to restore the sense of touch in paralyzed patients

Yesterday, CIRM-funded scientists at UCLA published an interesting study that sheds light on the development of sensory neurons, a type of nerve cell that is damaged in patients with spinal cord injury. Their early-stage findings could potentially, down the road, lead to the development of stem cell-based treatments that rebuild the sensory nervous system in paralyzed people that have lost their sense of touch.

Dr. Samantha Butler, a CIRM grantee and professor at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, led the study, which was published in the journal eLife.

Restoring sensation

Butler and her team were interested in understanding the basic development of sensory interneurons in the spinal cord. These are nerve cells in the spinal cord that receive sensory signals from the environment outside the body (like heat, pain and touch) and relay these signals to the brain where the senses are then perceived.

Developing spinal cord injury treatments often focus on the loss of movement caused by damage to the motor neurons in the spine that control our muscles. However, the damage caused to sensory neurons in the spine can be just as debilitating to people with paralysis. Without being able to feel whether a surface is hot or cold, paralyzed patients can sustain serious burn injuries.

Butler commented in a UCLA news release that attempting to restoring sensation in paralyzed patients is just as important as restoring movement:

Samantha Butler

“The understanding of sensory interneuron development has lagged far behind that of another class of neurons—called motor neurons—which control the body’s ability to move. This lack in understanding belies the importance of sensation: it is at the core of human experience. Some patients faced with the reality of paralysis place the recovery of the sense of touch above movement.”

BMPs are important for sensory neuron development

To restore sensation in paralyzed patients, scientists need to replace the sensory neurons that are damaged in the spine. To create these neurons, Butler looked to proteins involved in the early development of the spinal cord called bone morphogenetic proteins or BMPs.

BMPs are an important family of signaling proteins that influence development of the embryo. Their signaling can determine the fate or identity of cells including cells that make up the developing spinal cord.

It was previously thought that the concentration of BMPs determined what type of sensory neuron a stem cell would develop into, but Butler’s team found the opposite in their research. By studying developing chick embryos, they discovered that the type, not the concentration, of BMP matters when determining what subtype of sensory neuron is produced. Increasing the amount of a particular BMP in the chick spinal cord only produced more of the same type of sensory interneuron rather than creating a different type.

Increasing the concentration of a certain type of BMP increases the production of the same categories of sensory interneurons (red and green). (Image credit: UCLA)

The scientists confirmed these findings using mouse embryonic stem cells grown in the lab. Interestingly a different set of BMPs were responsible for deciding sensory neuron fate in the mouse stem cell model compared to the chick embryo. But the finding that different BMPs determine sensory neuron identity was consistent.

So what and what’s next?

While this research is still in its early stages, the findings are important because they offer a better understanding of sensory neuron development in the spinal cord. This research also hints at the potential for stem cell-based therapies that replace or restore the function of sensory neurons in paralyzed patients.

Madeline Andrews, the first author of the study, concluded:

“Central nervous system injuries and diseases are particularly devastating because the brain and spinal cord are unable to regenerate. Replacing damaged tissue with sensory interneurons derived from stem cells is a promising therapeutic strategy. Our research, which provides key insights into how sensory interneurons naturally develop, gets us one step closer to that goal.”

The next stop on the team’s research journey is to understand how BMPs influence sensory neuron development in a human stem cell model. The UCLA news release gave a sneak preview of their plans in the coming years.

“Butler’s team now plans to apply their findings to human stem cells as well as drug testing platforms that target diseased sensory interneurons. They also hope to investigate the feasibility of using sensory interneurons in cellular replacement therapies that may one day restore sensation to paralyzed patients.”

UCLA launches CIRM-funded clinical trial using engineered blood stem cells to fight hard-to-treat cancers

It’s not uncommon for biomedical institutes as well as their funding partners to announce through press releases that a clinical trial they’re running has gotten off the ground and has started to enroll patients. For an outsider looking in, it may seem like they’re jumping the gun a bit. No patients have received the therapy. No cures have been declared. So why all the hubbub at the start?

The reality is this: the launch of a clinical trial isn’t a beginning. It represents many years of effort by many researchers and a lot of funding to take an idea and develop it into a tangible product that has been given clearance to be tested in people to potentially save their lives. That’s why this important milestone deserves to be recognized. So, we were excited to get the word out, in the form of a press release , that UCLA had announced this morning the launch of a CIRM-funded clinical trial testing a therapy for hard-to-treat cancers.

The UCLA clinical trial procedure will genetically alter a patient’s hematopoietic stem cells and T cells to give rise to a steady supply of T cells that are efficient cancer killers.

It’s estimated that metastasis, or the spread of cancer to other parts of the body, is responsible for 90% of cancer deaths. Though radiation and chemotherapy treatments can stop a tumor in its tracks, a small population of cancer stem cells in the tumor lie dormant and can evade those anti-cancer approaches. Because of their unlimited potential to divide, the cancer stem cells regrow the tumor leading to its inevitable return and spread. Oncologists clearly need new approaches to help patients with this unmet medical need.

That’s where today’s clinical trial launch comes into the picture. Dr. Antonio Ribas, a member of the UCLA Broad Stem Cell Research Center, and his team will genetically engineer cancer-killing white blood cells called T cells and blood-forming stem cells collected from patients to produce a protein receptor that recognizes a protein found almost exclusively on the surface of many types of cancer. When the T cells are transfused back into the patient, they can more efficiently track down and eradicate hard-to-treat cancer stem cells. At the same time, the transfused blood stem cells – which specialize into all the various immune system cells – will provide a long-term supply of T cells for continued protection against reoccurrence of the tumor.

“Few options exist for the treatment of patients whose cancers have metastasized due to resistance to current therapies,” Ribas said in the UCLA press release. “This clinical trial will allow us to try a new approach that engineers the body’s immune system to fight metastasized tumors similar to how it fights germs and viruses.”

 

And as Dr. Maria Millan, CIRM’s President & CEO (interim), described in our accompanying press release, CIRM will be an ever-present partner to help Ribas’ team get the clinical trial smoothly out of the starting gate and provide the support needed to carry the therapy to its completion:

“This trial is the first step in developing a therapy that could alleviate the complications resulting from cancer metastases as well as potentially improving outcomes in cancer patients where there are currently no effective treatment options. We are confident that CIRM’s funding and partnership, in combination with the expertise provided by our Alpha Stem Cell Clinic network, will give provide critical support for the successful conduct of this important clinical trial.”

 

 

 

To learn more about this clinical trial, visit its page at clinicaltrials.gov. If you think you might be eligible to enroll, please contact Clinical Research Coordinator Justin Tran by email at justintran@mednet.ucla.edu or by phone at 310-206-2090.

Targeting hair follicle stem cells could be the key to fighting hair loss

Chia Pets make growing hair look easy. You might not be familiar with these chia plant terracotta figurines if you were born after the 80s, but I remember watching commercials growing up and desperately wanting a “Chia Pet, the pottery that grows!”

My parents eventually caved and got me a Chia teddy bear, and I was immediately impressed by how easy it was for my bear to grow “hair”. All I needed to do was to sprinkle water over the chia seeds and spread them over my chia pet, and in three weeks, voila, I had a bear that had sprouted a lush, thick coat of chia leaves.

These days, you can order Chia celebrities and even Chia politicians. If only treating hair loss in humans was as easy as growing sprouts on the top of Chia Mr. T’s head…

Activating Hair Follicle Stem Cells, the secret to hair growth?

That day might come sooner than we think thanks to a CIRM-funded study by UCLA scientists.

Published today in Nature Cell Biology, the UCLA team reported a new way to boost hair growth that could eventually translate into new treatments for hair loss. The study was spearheaded by senior authors Heather Christofk and William Lowry, both professors at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Christofk and Lowry were interested in understanding the biology of hair follicle stem cells (HFSCs) and how their metabolism (the set of chemical changes required for a cell to sustain itself) plays a role in hair growth. HFSCs are adult stem cells that live in the hair follicles of our skin. They are typically inactive but can quickly “wake up” and actively divide when a new hair growth cycle is initiated. When HFSCs fail to activate, hair loss occurs.

A closer look at HFSCs in mice revealed that these stem cells are dependent on the products of the glycolytic pathway, a metabolic pathway that converts the nutrient glucose into a metabolite called pyruvate, to stimulate their activation. The HFSCs have a choice, they can either give the pyruvate to their mitochondria to produce more energy, or they can break down the pyruvate into another metabolite called lactate.

The scientists found that if they tipped the balance towards producing more lactate, the HFSCs activated and induced hair growth. On the other hand, if they blocked lactate production, HFSCs couldn’t activate and new hair growth was blocked.

In a UCLA news release, Lowry explained the novel findings of their study,

“Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.”

New drugs for hair loss?

In the second half of the study, the UCLA team went on the hunt for drugs that promote lactate production in HFSCs in hopes of finding new treatment strategies to battle hair loss. They found two drugs that boosted lactate production when applied to the skin of mice. One was called RCGD423, which activates the JAK-Stat signaling pathway and stimulates lactate production. The other drug, UK5099, blocks the entry of pyruvate into the mitochondria, thereby forcing HFSCs to turn pyruvate into lactate resulting in hair growth. The use of both drugs for boosting hair growth are covered by provisional patent applications filed by the UCLA Technology Development Group.

Untreated mouse skin showing no hair growth (left) compared to mouse skin treated with the drug UK5099 (right) showing hair growth. Credit: UCLA Broad Stem Cell Center/Nature Cell Biology

Aimee Flores, the first author of the study, concluded by explaining why using drugs to target the HFSC metabolism is a promising approach for treating hair loss.

“Through this study, we gained a lot of interesting insight into new ways to activate stem cells. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think we’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; I’m looking forward to the potential application of these new findings for hair loss and beyond.”

If these hair growth drugs pan out, scientists might give Chia Pets a run for their money.

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.

 

 

 

 

 

World Sickle Cell Day: A View from the Front Line

June 19th is World Sickle Cell Day. Sickle cell disease is an inherited blood disorder that causes normally round red blood cells to take on an abnormal sickle shape, resulting in clogged arteries, severe pain, increased risk of stroke and reduced life expectancy. To mark the occasion we asked Nancy M. Rene to write a guest blog for us. Nancy is certainly qualified; she is the grandmother of a child with sickle cell disease, and the co-founder of Axis Advocacy, a non-profit advocating for those with sickle cell disease and their families.

Nancy ReneOn this World Sickle Cell Day, 2017, we can look back to the trailblazers in the fight against Sickle Cell Disease.  More than 40 years ago, the Black Panther Party established the People’s Free Medical Clinics in several cities across the country. One of the functions of these free clinics: to screen people for sickle cell disease and sickle cell trait. This life-saving screening began  in 1971.

Around that same time, President Richard Nixon allocated $10 million to begin the National Sickle Cell Anemia Control Act. This included counseling and screening, educational activities, and money for research.

In the early part of the twentieth century, most children with sickle cell died before their fifth birthday. With newborn screening available nationwide, the use of penicillin to prevent common infections, and the finding that hydroxyurea was useful in fighting the disease, life expectancy began to improve.

For much of the twentieth century, people with sickle cell disease felt that they were fighting the fight alone, knowledgeable doctors were scarce and insurance was often denied.

Making progress

As we moved into the twenty-first century, patients and families found they had some powerful allies. The National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) joined the battle.  In 2016 the NIH held its tenth annual international conference on sickle cell disease that featured speakers from all over the world.  Participants were able to learn about best practices in Europe, Africa, India, and South America.

Sickle Cell centers at Howard University, the Foundation for Sickle Cell Disease Research, and other major universities across the country are pointing the way to the best that medicine has to offer.

Last year, the prestigious American Society of Hematology (ASH) launched an initiative to improve understanding and treatment of sickle cell disease.  Their four-point plan includes education, training, advocacy, and expanding its global reach.

Just last month, May 2017, the FDA looked at Endari, developed by Emmaus Medical in Torrance, California.  It is the first drug specifically developed for sickle cell disease to go through the FDA’s approval process. We should have a decision on whether or not the drug goes to market in July.

The progress that had been made up to the beginning of the twenty-first century was basically about alleviating the symptoms of the disease: the sickling, the organ damage and the pervasive anemia. But a cure was still elusive.

But in 2004, California’s Stem Cell Agency, CIRM, was created and it was as if the gates had opened.

Researchers had a new source of funding to enable  them to work on Sickle Cell Disease and many other chronic debilitating diseases at the cellular level. Scientists like Donald Kohn at UCLA, were able to research gene editing and find ways to use autologous bone marrow transplants to actually cure people with sickle cell. While some children with sickle cell have been cured with traditional bone marrow transplants, these transplants must come from a matched donor, and for most patients, a matched donor is simply not available. CIRM has provided the support needed so that researchers are closing in on the cure. They are able to share strategies with doctors and researchers throughout the world

And finally, support from the federal government came with the passage of the Affordable Care Act and adequate funding for the NIH, CDC, the Health Resources and Services Administration (HRSA), and FDA.

Going backwards

And yet, here we are, World Sickle Cell Day, 2017.

Will this be a case of one step forward two steps back?

Are we really going back to the time when people with Sickle Cell Disease could not get health insurance because sickle cell is a pre-existing condition, to the time when there was little money and no interest in research or professional training, to a time when patients and their families were fighting this fight alone?

For all of those with chronic disease, it’s as if we are living a very bad dream.

Time to wake up

For me, I want to wake up from that dream.  I want to look forward to a future where patients and families, where Joseph and Tiffany and Marissa and Ken and Marcus and all the others, will no longer have to worry about getting well-informed, professional treatment for their disease.

Where patients will no longer fear going to the Emergency Room

Where doctors and researchers have the funding they need to support them in their work toward the cure,

Where all children, those here in the United States along with those in Africa, India, and South America, will have access to treatments that can free them from pain and organ damage of sickle cell disease.

And where all people with this disease can be cured.