CIRM-funded kidney transplant procedure eyeing faster approval

Kidney transplant surgery.

Medeor Therapeutics, which is running a CIRM-funded clinical trial to help people getting kidney transplants, just got some really good news. The US Food and Drug Administration (FDA) has just granted their product Regenerative Medicine Advanced Therapy (RMAT) designation. That’s a big deal because it means they may be able to apply for faster review and approval and get their therapy to more patients faster.

Here’s why that RMAT designation matters.

Over 650,000 Americans suffer from end-stage kidney disease – a life-threatening condition caused by the loss of kidney function. The best available treatment for these patients is a kidney transplant from a genetically matched living donor. However, patients who receive a transplant must take life-long immunosuppressive drugs to prevent their immune system from rejecting the transplanted organ. Over time, these drugs are toxic and can increase a patient’s risk of infection, heart disease, cancer and diabetes.  Despite these drugs, many patients still lose transplanted organs due to rejection.

To tackle this problem Medeor is developing a stem cell-based therapy called MDR-101. This is being tested in a Phase 3 clinical trial and it’s hoped it will eliminate the need for immunosuppressive drugs in genetically matched kidney transplant patients.

The company takes blood-forming stem cells and immune cells from the organ donor and infuses them into the patient receiving the donor’s kidney. Introducing the donor’s immune cells into the patient creates a condition called “mixed chimerism” where immune cells from the patient and the donor are able to co-exist. In this way, the patient’s immune system is able to adapt to and tolerate the donor’s kidney, potentially eliminating the need for the immunosuppressive drugs that are normally necessary to prevent transplant rejection.

So how does getting RMAT designation help that? Well, the FDA created the RMAT program to help speed up the development and review of regenerative medicine therapies that can treat, modify, reverse, or cure a serious condition. If MDR-101shows it is both safe and effective RMAT could help it get faster approval for wider use.

In a news release Giovanni Ferrara, President and CEO of Medeor, welcomed the news.

“This important designation underscores the tremendous unmet medical need for alternatives to today’s immunosuppressive therapies for transplantation. We have the potential to help people live longer, healthier lives without the need for high dose and chronic immunosuppression and we thank the FDA for this designation that will assist us progressing as efficiently as possible toward a commercially available product.”

This is the seventh CIRM-supported project that has been granted RMAT designation. The others are jCyte, Lineage, Humacyte, St. Jude’s/UCSF X-linked SCID, Poseida, Capricor

CIRM-funded therapy helps “bubble babies” lead a normal life

Ja’Ceon Golden; ‘cured” of SCID

At CIRM we are very cautious about using the “c” word. Saying someone has been “cured” is a powerful statement but one that loses its meaning when over used or used inappropriately. However, in the case of a new study from U.C. San Francisco and St. Jude Children’s Research Hospital in Memphis, saying “cure” is not just accurate, it’s a celebration of something that would have seemed impossible just a few years ago.

The research focuses on children with a specific form of Severe Combined Immunodeficiency (SCID) called X-Linked SCID. It’s also known as “bubble baby” disease because children born with this condition lack a functioning immune system, so even a simple infection could be fatal and in the past they were kept inside sterile plastic bubbles to protect them.

In this study, published in the New England Journal of Medicine, researchers took blood stem cells from the child and, in the lab, genetically re-engineered them to correct the defective gene, and then infused them back into the child. Over time they multiplied and created a new blood supply, one free of the defect, which helped repair the immune system.

In a news release Dr. Ewelina Mamcarz, the lead author of the study, announced that ten children have been treated with this method.

“These patients are toddlers now, who are responding to vaccinations and have immune systems to make all immune cells they need for protection from infections as they explore the world and live normal lives. This is a first for patients with SCID-X1.”

The ten children were treated at both St. Jude and at UCSF and CIRM funded the UCSF arm of the clinical trial.

The story, not surprisingly, got a lot of attention in the media including this fine piece by CNN.

Oh, and by the way we are also funding three other clinical trials targeting different forms of SCID. One with UCLA’s Don Kohn,  one with Stanford’s Judy Shizuru, and one with UCSF’s Mort Cowan

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

Ayaan Isaacs, health24

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

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

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

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

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

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

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

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

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


Related Links:

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

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

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

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

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

Unique delivery system

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

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

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

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

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

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

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

Saving Ronnie: Stem Cell & Gene Therapy for Fatal Bubble Baby Disease [Video]

During this second week of the Month of CIRM, we’ve been focusing on the people who are critical to accomplishing our mission to accelerate stem cell treatments to patients with unmet medical needs.

These folks include researchers, like Clive Svendsen and his team at Cedars-Sinai Medical Center who are working tirelessly to develop a stem cell therapy for ALS. My colleague Karen Ring, CIRM’s Social Media and Website Manager, featured Dr. Svendsen and his CIRM-funded clinical trial in Monday’s blog. And yesterday, in recognition of Stem Cell Awareness Day, Kevin McCormack, our Senior Director of Public Communications, blogged about the people within the stem cell community who have made, and continue to make, the day so special.

Today, in a new video, I highlight a brave young patient, Ronnie, and his parents who decided to participate in a CIRM-funded clinical trial run by St. Jude Children’s Research Hospital and UC San Francisco in an attempt to save Ronnie’s life from an often-fatal disease called severe combined immunodeficiency (SCID). This disorder, also known as bubble baby disease, leaves newborns without a functioning immune system which can turn a simple cold into a potentially deadly infection.

Watch this story’s happy ending in the video above.

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.