Joining the movement to fight rare diseases

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It’s hard to think of something as being rare when it affects up to 30 million Americans and 300 million people worldwide. But the truth is there are more than 6,000 conditions – those affecting 200,000 people or fewer – that are considered rare.  

Today, February 28th, is Rare Disease Day. It’s a day to remind ourselves of the millions of people, and their families, struggling with these diseases. These conditions are also called or orphan diseases because, in many cases, drug companies were not interested in adopting them to develop treatments.

At the California Institute for Regenerative Medicine (CIRM), we have no such reservations. In fact last Friday our governing Board voted to invest almost $12 million to support a clinical trial for IPEX syndrome. IPEX syndrome is a condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. This leads to the development of Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive. It’s diagnosed in infancy, most of those affected are boys, and it is often fatal.

Taylor Lookofsky (who has IPEX syndrome) and his father Brian

IPEX is one of two dozen rare diseases that CIRM is funding a clinical trial for. In fact, more than one third of all the projects we fund target a rare disease or condition. Those include:

Some might question the wisdom of investing hundreds of millions of dollars in conditions that affect a relatively small number of patients. But if you see the faces of these patients and get to know their families, as we do, you know that often agencies like CIRM are their only hope.

Dr. Maria Millan, CIRM’s President and CEO, says the benefits of one successful approach can often extend far beyond one rare disease.

“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives. Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders.”

CIRM is proud to fund and spread awareness of rare diseases and invites you to watch this video about how they affect families around the world.

Stem Cell Agency Board Approves Funding for Rare Immune Disorder

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Taylor Lookofsky (center), a person with IPEX syndrome, with his father Brian and Dr. Rosa Bacchetta

IPEX syndrome is a rare condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. The syndrome mostly affects boys, is diagnosed in the first year of life and is often fatal. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) invested almost $12 million in a therapy being tested in a clinical trial to help these patients.

Children born with IPEX syndrome have abnormalities in the FOXP3 gene. This gene controls the production of a type of immune cell called a T Regulatory or Treg cell. Without a normal FOXP3 +Treg cells other immune cells attack the body leading to the development of IPEX syndrome, Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive.

Current treatments involve the use of steroids to suppress the immune system – which helps ease symptoms but doesn’t slow down the progression of the disease – or a bone marrow stem cell transplant.  However, a transplant requires a healthy, closely matched donor to reduce the risk of a potentially fatal transplant complication called graft vs host disease, in which the donated immune cells attack the recipient’s tissues.

Dr. Rosa Bacchetta and her team at Stanford University have developed a therapy using the patient’s own natural CD4 T cells that, in the lab, have been genetically modified to express the FoxP3 gene and converted into Treg cells. Those cells are then re-infused into the patient with a goal of determining if this approach is both safe and beneficial. Because the cells come from the patients there will be fewer concerns about the need for immunosuppressive treatment to stop the body rejecting the cells. It will also help avoid the problems of finding a healthy donor and graft vs host disease.

Dr. Bacchetta has received approval from the Food and Drug Administration (FDA) to test this approach in a Phase 1 clinical trial for patients suffering with IPEX syndrome.

“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives,” says Dr. Maria T. Millan, the President and CEO of CIRM. “Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders resulting from dysfunctional regulatory T cells.”

In addition to a strong scientific recommendation to fund the project the review team also praised it for the applicants’ commitment to the principles of Diversity, Equity and Inclusion in their proposal. The project proposes a wide catchment area, with a strong focus on enrolling people who are low-income, uninsured or members of traditionally overlooked racial and ethnic minority communities.

CIRM-Funded Study Helping Babies Battle a Deadly Immune Disorder Gets Boost from FDA

Hataalii Begay, age 4, first child treated with UCSF gene therapy for Artemis-SCID

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When Hataalii Begay was born in a remote part of the Navajo nation he was diagnosed with a rare, usually fatal condition. Today, thanks to a therapy developed at UCSF and funded by CIRM, he’s a normal healthy four year old boy running around in cowboy boots.

That stem cell therapy could now help save the lives of other children born with this deadly immune disorder because it has been granted fast-track review status by the US Food and Drug Administration (FDA).

The California Institute for Regenerative Medicine (CIRM) has invested $12 million to test this therapy in a clinical trial at UC San Francisco.

The disorder is Artemis-SCID, a form of severe combined immunodeficiency disease. Children born with this condition have no functioning immune system so even a simple infection can prove life-threatening or fatal.

Currently, the only approved treatment for Artemis-SCID is a bone-marrow transplant, but many children are unable to find a healthy matched donor for that procedure. Even when they do find a donor they often need regular injections of immunoglobulin to boost their immune system.

In this clinical trial, UCSF Doctors Mort Cowan and Jennifer Puck are using the patient’s own blood stem cells, taken from their bone marrow. In the lab, the cells are modified to correct the genetic mutation that causes Artemis-SCID and then re-infused back into the patients. The goal is that over the course of several months these cells will create a new blood supply, one that is free of Artemis-SCID, and that will in turn help repair the child’s immune system.

So far the team has treated ten newly-diagnosed infants and three older children who failed transplants. Dr. Cowan says early data from the trial is encouraging. “With gene therapy, we are seeing these babies getting older. They have normal T-cell immunity and are getting immunized and vaccinated. You wouldn’t know they had any sort of condition if you met them; it’s very heartening.”

Because of that encouraging data, the FDA is granting this approach Regenerative Medicine Advanced Therapy (RMAT) designation. RMAT is a fast-track designation that can help speed up the development, review and potential approval of treatments for serious or life-threatening diseases.

“This is great news for the team at UCSF and in particular for the children and families affected by Artemis-SCID,” says Dr. Maria T. Millan, the President and CEO of CIRM. “The RMAT designation means that innovative forms of cell and gene therapies like this one may be able to accelerate their route to full approval by the FDA and be available to all the patients who need it.”

Looking back and looking forward: good news for two CIRM-supported studies

Dr. Rosa Bacchetta on the right with Brian Lookofsky (left) and Taylor Lookofsky after CIRM funded Dr. Bacchetta’s work in October 2019. Taylor has IPEX syndrome

It’s always lovely to end the week on a bright note and that’s certainly the case this week, thanks to some encouraging news about CIRM-funded research targeting blood disorders that affect the immune system.

Stanford’s Dr. Rosa Bacchetta and her team learned that their proposed therapy for IPEX Syndrome had been given the go-ahead by the Food and Drug Administration (FDA) to test it in people in a Phase 1 clinical trial.

IPEX Syndrome (it’s more formal and tongue twisting name is Immune dysregulation Polyendocrinopathy Enteropathy X-linked syndrome) is a life-threatening disorder that affects children. It’s caused by a mutation in the FOXP3 gene. Immune cells called regulatory T Cells normally function to protect tissues from damage but in patients with IPEX syndrome, lack of functional Tregs render the body’s own tissues and organs to autoimmune attack that could be fatal in early childhood. 

Current treatment options include a bone marrow transplant which is limited by available donors and graft versus host disease and immune suppressive drugs that are only partially effective. Dr. Rosa Bacchetta and her team at Stanford will use gene therapy to insert a normal version of the FOXP3 gene into the patient’s own T Cells to restore the normal function of regulatory T Cells.

This approach has already been accorded an orphan drug and rare pediatric disease designation by the FDA (we blogged about it last year)

Orphan drug designation is a special status given by the Food and Drug Administration (FDA) for potential treatments of rare diseases that affect fewer than 200,000 in the U.S. This type of status can significantly help advance treatments for rare diseases by providing financial incentives in the form of tax credits towards the cost of clinical trials and prescription drug user fee waivers.

Under the FDA’s rare pediatric disease designation program, the FDA may grant priority review to Dr. Bacchetta if this treatment eventually receives FDA approval. The FDA defines a rare pediatric disease as a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years and affects fewer than 200,000 people in the U.S.

Congratulations to the team and we wish them luck as they begin the trial.

Dr. Donald Kohn, Photo courtesy UCLA

Someone who needs no introduction to regular readers of this blog is UCLA’s Dr. Don Kohn. A recent study in the New England Journal of Medicine highlighted how his work in developing a treatment for severe combined immune deficiency (SCID) has helped save the lives of dozens of children.

Now a new study in the journal Blood shows that those benefits are long-lasting, with 90% of patients who received the treatment eight to 11 years ago still disease-free.

In a news release Dr. Kohn said: “What we saw in the first few years was that this therapy worked, and now we’re able to say that it not only works, but it works for more than 10 years. We hope someday we’ll be able to say that these results last for 80 years.”

Ten children received the treatment between 2009 and 2012. Nine were babies or very young children, one was 15 years old at the time. That teenager was the only one who didn’t see their immune system restored. Dr. Kohn says this suggests that the therapy is most effective in younger children.

Dr. Kohn has since modified the approach his team uses and has seen even more impressive and, we hope, equally long-lasting results.

Celebrating Stem Cell Awareness Day

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The second Wednesday in October is celebrated as Stem Cell Awareness Day. It’s an event that CIRM has been part of since then Governor Arnold Schwarzenegger launched it back in 2008 saying: ”The discoveries being made today in our Golden State will have a great impact on many around the world for generations to come.”

In the past we would have helped coordinate presentations by scientists in schools and participated in public events. COVID of course has changed all that. So, this year, to help mark the occasion we asked some people who have been in the forefront of making Governor Schwarzenegger’s statement come true, to share their thoughts and feelings about the day. Here’s what they had to say.

What do you think is the biggest achievement so far in stem cell research?

Dr. Jan Nolta

Jan Nolta, PhD., Director of the Stem Cell Program at UC Davis School of Medicine, and directs the new Institute for Regenerative Cures. “The work of Don Kohn and his UCLA colleagues and team members throughout the years- developing stem cell gene therapy cures for over 50 children with Bubble baby disease. I was very fortunate to work with Don for the first 15 years of my career and know that development of these cures was guided by his passion to help his patients.

Dr. Clive Svendsen

Clive Svendsen, PhD. Director, Board of Governors Regenerative Medicine Institute at Cedars-Sinai: “Without a doubt the discovery of how to make human iPSCs by Shinya Yamanaka and Jamie Thomson.”

When people ask you what kind of impact CIRM and stem cell research has had on your life what do you say?

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

Pawash Priyank and Upasana Thakur, parents of Ronnie, who was born with a life-threatening immune disorder but is thriving today thanks to a CIRM-funded clinical trial at UC San Francisco. “This is beyond just a few words and sentences but we will give it a shot. We are living happily today seeing Ronnie explore the world day by day, and this is only because of what CIRM does every day and what Stem cell research has done to humanity. Researchers and scientists come up with innovative ideas almost every day around the globe but unless those ideas are funded or brought to implementation in any manner, they are just in the minds of those researchers and would never be useful for humanity in any manner. CIRM has been that source to bring those ideas to the table, provide facilities and mechanisms to get those actually implemented which eventually makes babies like Ronnie survive and see the world. That’s the impact CIRM has. We have witnessed and heard several good arguments back in India in several forums which could make difference in the world in different sectors of lives but those ideas never come to light because of the lack of organizations like CIRM, lack of interest from people running the government. An organization like CIRM and the interest of the government to fund them with an interest in science and technology actually changes the lives of people when some of those ideas come to see the light of real implementation. 

What are your biggest hopes for the future at UC Davis?

Jan Nolta, PhD: “The future of stem cell and gene therapy research is very bright at UC Davis, thanks to CIRM and our outstanding leadership. We currently have 48 clinical trials ongoing in this field, with over 20 in the pipeline, and are developing a new education and technology complex, Aggie Square, next to the Institute for Regenerative Cures, where our program is housed. We are committed to our very diverse patient population throughout the Sacramento region and Northern California, and to expanding and increasing the number of novel therapies that can be brought to all patients who need them.”

What are your biggest hopes for the future at Cedars-Sinai?

Clive Svendsen, PhD: “That young investigators will get CIRM or NIH funding and be leaders in the regenerative medicine field.”

What do you hope is the future for stem cell research?

Pawash Priyank and Upasana Thakur: “We always have felt good about stem cell therapy. For us, a stem cell has transformed our lives completely. The correction of sequencing in the DNA taken out of Ronnie and injecting back in him has given him life. It has given him the immune system to fight infections. Seeing him grow without fear of doing anything, or going anywhere gives us so much happiness every hour. That’s the impact of stem cell research. With right minds continuing to research further in stem cell therapy bounded by certain good processes & laws around (so that misuse of the therapy couldn’t be done) will certainly change the way treatments are done for certain incurable diseases. I certainly see a bright future for stem cell research.”

On a personal note what is the moment that touched you the most in this journey.

Jan Nolta, PhD: “Each day a new patient or their story touches my heart. They are our inspiration for working hard to bring new options to their care through cell and gene therapy.”

Clive Svendsen, PhD: “When I realized we would get the funding to try and treat ALS with stem cells”

How important is it to raise awareness about stem cell research and to educate the next generation about it?

Pawash Priyank and Upasana Thakur: “Implementing stem cell therapy as a curriculum in the educational systems right from the beginning of middle school and higher could prevent false propaganda of it through social media. Awareness among people with accurate articles right from the beginning of their education is really important. This will also encourage the new generation to choose this as a subject in their higher studies and contribute towards more research to bring more solutions for a variety of diseases popping up every day.”

National Academy of Medicine honors CIRM Grantees

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As someone who is not always as diligent as he would like to be about sending birthday cards on time, I’m used to sending belated greetings to people. So, I have no shame in sending belated greetings to four CIRM grantees who were inducted into the National Academy of Medicine in 2020.

I say four, but it’s really three and a half. I’ll explain that later.

Being elected to the National Academy of Medicine is, in the NAM’s own modest opinion, “considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.”

To be fair, NAM is right. The people elected are among the best and brightest in their field and membership is by election from the other members of NAM, so they are not going to allow any old schmuck into the Academy (which could explain why I am still waiting for my membership).

The CIRM grantees elected last year are:

Dr. Antoni Ribas: Photo courtesy UCLA

Antoni Ribas, MD, PhD, professor of medicine, surgery, and molecular and medical pharmacology, U. C. Los Angeles.

Dr. Ribas is a pioneer in cancer immunology and has devoted his career to developing new treatments for malignant melanoma. When Dr. Ribas first started malignant melanoma was an almost always fatal skin cancer. Today it is one that can be cured.

In a news release Dr. Ribas said it was a privilege to be honored by the Academy: “It speaks to the impact immunotherapy has played in cancer research. When I started treating cases of melanoma that had metastasized to other organs, maybe 1 in 20 responded to treatment. Nobody in their right mind wanted to be a specialist in this field. It was the worst of the worst cancers.”

Looks like he chose his career path wisely.

Dr. Jeffrey Goldberg: Photo courtesy Stanford

Jeffrey Louis Goldberg, MD, PhD, professor and chair of ophthalmology, Stanford University, Palo Alto, Calif.

Dr. Goldberg was honored for his contribution to the understanding of vision loss and ways to reverse it. His lab has developed artificial retinas that transmit images down the optic nerve to the brain through tiny silicon chips implanted in the eye. He has also helped use imaging technology to better improve our ability to detect damage in photoreceptor cells (these are cells in the retina that are responsible for converting light into signals that are sent to the brain and that give us our color vision and night vision)

In a news release he expressed his gratitude saying: “I look forward to serving the goals of the National Academies, and to continuing my collaborative research efforts with my colleagues at the Byers Eye Institute at Stanford and around the world as we further our efforts to combat needless blindness.”

Dr. Mark Anderson; photo courtesy UCSF

Mark S. Anderson, MD, PhD, professor in Diabetes Research, Diabetes Center, U. C. San Francisco.

Dr. Anderson was honored for being a leader in the study of autoimmune diseases such as type 1 diabetes. This focus extends into the lab, where his research examines the genetic control of autoimmune diseases to better understand the mechanisms by which immune tolerance is broken.

Understanding what is happening with the immune system, figuring out why it essentially turns on the body, could one day lead to treatments that can stop that, or even reverse it by boosting immune activity.

Dr. John Dick: Photo courtesy University Health Network, Toronto

Remember at the beginning I said that three and a half CIRM grantees were elected to the Academy, well, Canadian researcher, Dr. John Dick is the half. Why? Well, because the award we funded actually went to UC San Diego’s Dennis Carson but it was part of a Collaborative Funding Partnership Program with Dr. Dick at the University of Toronto. So, we are going to claim him as one of our own.

And he’s a pretty impressive individual to partner with. Dr. Dick is best known for developing a test that led to the discovery of leukemia stem cells. These are cells that can evade surgery, chemotherapy and radiation and which can lead to patients relapsing after treatment. His work helped shape our understanding of cancer and revealed a new strategy for curing it.

Prime Time for Rocket

Rocket Pharmaceuticals, a company that specializes in developing genetic therapies for rare childhood disorders, just got a big boost from the European Medicines Agency (EMA). They were given a Priority Medicines (PRIME) designation for their therapy for Leukocyte Adhesion Deficiency-1 (LAD-1).

CIRM is funding ($6.56 million) Rocket’s clinical trial for LAD-I, an immune disorder that leaves patients vulnerable to repeated infections that often results in death within the first two years of life. The therapy involves taking some of the child’s own blood stem cells and, in the lab, correcting the mutation that causes LAD-I, then returning those cells to the patient. Hopefully those blood stem cells then create a new, healthy blood supply and repair the immune system.

The therapy, called RP-L201, is already showing promise in the clinical trial, hence the PRIME designation. The program was set up to help speed up development and evaluation of therapies that could help patients who have limited treatment options. Getting a PRIME designation means it is considered a priority by EMA and could reach patients sooner.

In the US, Rocket has won similar recognition from the Food and Drug Administration (FDA) and has been granted Regenerative Medicine Advanced Therapy (RMAT), Rare Pediatric Disease, and Fast Track designations.

In a news release Kinnari Patel, President and Chief Operating Officer of Rocket, said the designation showed that regulators understand the urgent need to develop a therapy for patients with LAD-1. “More than half of LAD-I patients suffer with a severe variant in which mortality occurs in up to 75% of young children who don’t receive a successful bone marrow transplant by the age of two. Securing all possible accelerated designations will enable us to collaborate with both the FDA and EMA to speed the development and delivery of a potential treatment for these patients.  We look forward to sharing initial Phase 2 data from our potentially registration-enabling LAD-I trial in the second quarter of 2021.”

That trial has now completed enrolling patients (nine altogether) but their treatments are not yet complete. LAD-1 patients with severe disease have low levels of a key protein called CD18, usually less than 2%. Of the first three patients treated in this trial CD18 levels are all higher than the 4-10% threshold considered necessary for these children to survive into adulthood. Another encouraging sign is that there were no serious side effects from the therapy.

Obviously there is still a long way to go before we know if this therapy really works, but the PRIME designation – along with the similar ones in the US – are recognition that this is a very promising start.

Going the extra mile to save a patient’s life

You can tell an awful lot about a company by the people it hires and the ability it gives them to do their job in an ethical, principled way. By that measure Rocket Pharma is a pretty darn cool company.

Rocket Pharma is running a CIRM-funded clinical trial for Leukocyte Adhesion Deficiency-I (LAD-I), a rare genetic immune disorder that leaves patients vulnerable to repeated infections that often results in death within the first two years of life. The therapy involves taking some of the child’s own blood stem cells and, in the lab, correcting the mutation that causes LAD-I, then returning those cells to the patient. Hopefully those blood stem cells then create a new, healthy blood supply and repair the immune system.

So far, they have treated the majority of the nine patients in this Phase 1/2 clinical trial. Here’s the story of three of those children, all from the same family. Every patient’s path to the treatment has been uniquely challenging. For one family, it’s been a long, rough road, but one that shows how committed Rocket Pharma (Rocket) is to helping people in need.

The patient, a young girl, is from India. The family has already lost one child to what was almost certainly LAD-I, and now they faced the very real prospect of losing their daughter too. She had already suffered numerous infections and the future looked bleak. Fortunately, the team at Rocket heard about her and decided they wanted to help enroll her in their clinical trial.

Dr. Gayatri Rao, Rocket Pharmaceuticals

Dr. Gayatri Rao, the Global Program Head for the LAD-I therapy, this patient was about 6 months old when they heard about her: “She had already been in and out of the hospital numerous times so the family were really interested in enrolling the patient. But getting the family to the US was daunting.”

Over the course of several months, the team at Rocket helped navigate the complicated immigration process. Because the parents and child would need to make several trips to the US for treatment and follow-up exams they would need multiple-entry visas. “Just to get all the paper work necessary was a monumental task. Everything had to be translated because the family didn’t speak English. By the time the family flew to Delhi for their visa interview they had a dossier that filled a 3 inch binder.”  Rocket worked closely with partners in India to provide the family on-the-ground support every step of the way.  To help ensure the family received the visas they needed, Rocket also reached out to members of Congress and six members wrote in support of the family’s application.

Finally, everything fell into place. The family had the visas, all the travel arrangements were made. The Rocket team had even found an apartment near the UCLA campus where the family would stay during the treatment and stocked it with Indian food.

But on the eve of their flight to the US, the coronavirus pandemic hit. International flights were cancelled. Borders were closed. A year of work was put on hold and, more important, the little girl’s life hung in the balance.

Over the course of the next few months the little girl suffered several infections and had to be hospitalized. The family caught COVID and had to undergo quarantine till they recovered. But still the Rocket team kept working on a plan to bring them to the US. Finally, in late January, as vaccines became available and international flights opened up once again, the family were able to come to the US. One west-coast based Rocket team member even made sure that upon arriving to the apartment in UCLA, there was a home-cooked meal, a kitchen stocked with groceries, and handmade cards welcoming them to help transition the family into their new temporary “home.” They are now in living in that apartment near UCLA, waiting for the treatment to start.

Gayatri says it would have been easy to say: “this is too hard” and try to find another patient in the trial, but no one at Rocket wanted to do that: “Once a patient gets identified, we feel like we know them and the team feels invested in doing everything we can for them. We know it may not work out. But at the end of the day, we recognize that this child often has no other choices, and that motivates us to keep going despite the challenges.  If anything, this experience has taught us that with persistence and creativity, we can surmount these challenges.”

Maybe doing the right thing brings its own rewards, because this earlier this month Rocket was granted Regenerative Medicine Advanced Therapy (RMAT) designation for their treatment for LAD-I. This is a big deal because it means the therapy has already shown it appears to be safe and potentially beneficial to patients, so the designation means that if it continues to be safe and effective it may be eligible for a faster, more streamlined approval process. And that means it can get to the patients who need it, outside of a clinical trial, faster.

A word from our Chair, several in fact

In 2005, the New Oxford American Dictionary named “podcast” its word of the year. At the time a podcast was something many had heard of but not that many actually tuned in to. My how times have changed. Now there are some two million podcasts to chose from, at least according to the New York Times, and who am I to question them.

Yesterday, in the same New York Times, TV writer Margaret Lyons, wrote about how the pandemic helped turn her from TV to podcasts: “Much in the way I grew to prefer an old-fashioned phone call to a video chat, podcasts, not television, became my go-to medium in quarantine. With their shorter lead times and intimate production values, they felt more immediate and more relevant than ever before.”

I mention this because an old colleague of ours at CIRM, Neil Littman, has just launched his own podcast and the first guest on it was Jonathan Thomas, Chair of the CIRM Board. Their conversation ranged from CIRM’s past to the future of the regenerative field as a whole, with a few interesting diversions along the way. It’s fun listening. And as Margaret Lyons said it might be more immediate and more relevant than ever before.

CIRM-funded treatment gets orphan drug and rare pediatric disease designations from FDA

From left to right: Brian Lookofsky , Taylor Lookofsky, and Rosa Bacchetta, M.D.
Picture taken October 2019

Last year, CIRM awarded $5.53 million to Rosa Bacchetta, M.D. at Stanford University to complete the work necessary to conduct a clinical trial for IPEX syndrome. This is a rare disease caused by mutations in the FOXP3 gene, which leaves people with the condition vulnerable to immune system attacks on their organs and tissues. These attacks can be devastating, even fatal.

Flash forward to the present day and the CIRM-funded treatment that Dr. Bacchetta has been working on has received both an orphan drug and a rare pediatric disease designation from the Food and Drug Administration (FDA).

Orphan drug designation is a special status given by the Food and Drug Administration (FDA) for potential treatments of rare diseases that affect fewer than 200,000 in the U.S. This type of status can significantly help advance treatments for rare diseases by providing financial incentives in the form of tax credits towards the cost of clinical trials and prescription drug user fee waivers.

Under the FDA’s rare pediatric disease designation program, the FDA may grant priority review to Dr. Bacchetta if this treatment eventually receives FDA approval. The FDA defines a rare pediatric disease as a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years and affects fewer than 200,000 people in the U.S.

“The designations granted by the FDA are a strong encouragement for our team to meet the goal of submitting the IND in 2021 and start the clinical trial for IPEX patients who are so much looking forward to new therapeutic options.” said Dr. Bacchetta.

But this begs the question, what exactly is IPEX syndrome? What is the approach that Dr. Bacchetta is working on? For those of you interested in the deeper scientific dive, we will elaborate on this complex disease and promising approach.

IPEX syndrome is a rare disease that primarily affects males and is caused by a genetic mutation that leads to lack of function of specialized immune cells called regulatory T cells (Tregs).

Without functional Tregs, a patient’s own immune cells attack the body’s own tissues and organs, a phenomenon known as autoimmunity.  This affects many different areas such as the intestines, skin, and hormone-producing glands and can be fatal in early childhood. 

Current treatment options include a bone marrow transplant and immune suppressing drugs.  However, immune suppression is only partially effective and can cause severe side effects while bone marrow transplants are limited due to lack of matching donors.

Dr. Rosa Bacchetta and her team at Stanford will take a patient’s own blood in order to obtain CD4+ T cells.  Then, using gene therapy, they will insert a normal version of the mutated gene into the CD4+ T cells, allowing them to function like normal Treg cells.  These Treg-like cells would then be reintroduced back into the patient, hopefully creating an IPEX-free blood supply and resolving the autoimmunity.

Furthermore, if successful, this treatment could be adapted for treatment of other, more common, autoimmune conditions where Treg cells are the underlying problem.

The same day that CIRM approved funding for this approach, Taylor Lookofsky, a young man with IPEX syndrome, talked about the impact the condition has had on his life.

It’s a powerful reminder that syndromes like this, because they affect a small number of people, are often overlooked and have few resources devoted to finding new treatments and cures. After hearing Taylor’s story, you come to appreciate his courage and determination, and why the funding CIRM provides is so important in helping researchers like Dr. Bacchetta find therapies to help people like Taylor.

The full transcript of his talk can be accessed on a previous blog post.