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 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.

What is IPEX syndrome? A deeper dive into a CIRM funded award

Brian Lookofsky (left) and his son Taylor Lookofsky (right) at the CIRM Board meeting on October 31, 2019. Taylor is living with IPEX syndrome.

Last week we shared a powerful story of patient advocate Taylor Lookofsky, a young man with IPEX syndrome. In his speech, he talked about the impact the condition has had on his life. Taylor shared this speech a few weeks ago right after the CIRM Board awarded $5.53 million to Dr. Rosa Bacchetta for her work related to IPEX syndrome.

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 a lack of specialized immune cells called regulatory T cells (Tregs).

Without the presence of 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 correcting the problem.

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

The goal of this work is to complete the work necessary to conduct a clinical trial for IPEX syndrome.

The challenges of living with IPEX

Last week the CIRM Board awarded $5.53 million to Dr. Rosa Bacchetta at Stanford 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.

At the Board meeting Taylor Lookofsky, a young man with IPEX syndrome, talked about the impact the condition has had on his life. The transcript of his talk is below.

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 reading 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.

Brian Lookofsky (Taylor’s father), Taylor Lookofsky and Dr. Rosa Bacchetta at the CIRM Board meeting

“Good morning, my name is Taylor Lookofsky and I would first like to thank Rosa, who is one of the many doctors in my life. Rosa presented me with this amazing opportunity to come and speak to you today about my life and the challenges living with IPEX.

  • I’d like to give you some background into my health challenges I’ve faced my entire life. Now to give some context to my years of struggle, I am 28 years old, not 10 years younger as some may have assumed.
  • My first diagnosis came at the age of 1 ½ years old -type 1 diabetes.
  • Soon after being diagnosed with type 1 diabetes, I had to have a feeding tube inserted in my abdomen as I was restricted from eating almost all foods due to unknown food allergies. I was not allowed to ingest ANY food until the age of 6 years old. When I was finally introduced to food, any food ingested was tasteless and felt like sandpaper on my tongue since I had to train myself to eat.
  • Around age 10, I would be faced with the beginning of a never-ending battle with my dermatitis. I remember specific details where my mother had taken me to a dermatologist to try and figure out what was happening to my skin as it was red, blotchy, oozing. I remember shivering so badly that my mom had to ask the doctor’s office to turn the air down.
  • At age 18 I had been formally diagnosed with IPEX. I lost my hair and my skin started a battle that was more intense than any previous episode. I remember taking showers and clumps of my hair would fall out, and I would cry in the shower not knowing what was going on.
  • At age 20, I would go through the most horrific episode with my skin to date. I was bed ridden, on pain meds and could not sleep. I had gone to all of my doctors trying to figure out what had triggered this event, and no doctor could figure out what was happening, leaving me extremely frustrated, depressed and drained of all energy. I went to the burn center as a last resort and was then treated like a burn patient. To care for these wounds, I would bathe, take a sponge and physically scrape these wounds to keep them infection free and as clean as possible. When I would exit the bath, I felt like a dried-up sponge and my skin was so tight that any movement would make my skin crack open and start bleeding. To add to this, I had to use medicated wraps to help with the healing process.
  • In an ongoing attempt to treat my many symptoms, I took a series of medications that came with side effects. I have had at least 15 surgeries to remove squamous cells caused by one of the medications: In 2018, my colon perforated. As a result, I now have a colostomy bag.

The IPEX symptoms have affected me not just physically, but mentally as well. I had lost all my hair and growth has been permanently stunted, and I have not reached the point in puberty as my male counterparts. I would go day by day and see all my peers and be envious that they were tall, had beards and hair, had relationships, and the confidence that I was lacking and admittedly, still lack to this day at times.

I’ve felt hopeless because there have been so few treatment options and with the treatment currently available, I have tried hundreds of medications and creams, and have had my blood drawn countless times in hopes of finding a medication that works for me, or a cure for this insufferable disease. However, nothing. As a result, I have been battling depression singe age 20. There were days that went by where I thought “I just don’t want to be here if this is what life is going to be like.” 

The funding needed for Dr. Rosa’s therapy would be life changing in the way of new treatment options and potentially lead to a cure for this horrific disease.

I am determined to see that there is so much more to life than what society is telling me. I’ve decided that I would not conform to societies rules, and instead, tell society how I am going to live my unique and authentic life with IPEX.

I appreciate your time and consideration to fund this important research.”