It’s all about the patients

Ronnie, born with a fatal immune disorder now leading a normal life thanks to a CIRM-funded stem cell/gene therapy: Photo courtesy of his mum Upasana

Whenever you are designing something new you always have to keep in mind who the end user is. You can make something that works perfectly fine for you, but if it doesn’t work for the end user, the people who are going to work with it day in and day out, you have been wasting your time. And their time too.

At CIRM our end users are the patients. Everything we do is about them. Starting with our mission statement: to accelerate stem cell treatments to patients with unmet medical needs. Everything we do, every decision we make, has to keep the needs of the patient in mind.

So, when we were planning our recent 2020 Grantee Meeting (with our great friends and co-hosts UC Irvine and UC San Diego) one of the things we wanted to make sure didn’t get lost in the mix was the face and the voice of the patients. Often big conferences like this are heavy on science with presentations from some of the leading researchers in the field. And we obviously wanted to make sure we had that element at the Grantee meeting. But we also wanted to make sure that the patient experience was front and center.

And we did just that. But more on that in a minute. First, let’s talk about why the voice of the patient is important.

Some years ago, Dr. David Higgins, a CIRM Board member and patient advocate for Parkinson’s Disease (PD), said that when researchers are talking about finding treatments for PD they often focus on the dyskinesia, the trembling and shaking and muscle problems. However, he said if you actually asked people with PD you’d find they were more concerned with other aspects of the disease, the insomnia, anxiety and depression among other things. The key is you have to ask.

Frances Saldana, a patient advocate for research into Huntington’s disease

So, we asked some of our patient advocates if they would be willing to be part of the Grantee Meeting. All of them, without hesitation, said yes. They included Frances Saldana, a mother who lost three of her children to Huntington’s disease; Kristin MacDonald, who lost her sight to a rare disorder but regained some vision thanks to a stem cell therapy and is hoping the same therapy will help restore some more; Pawash Priyank, whose son Ronnie was born with a fatal immune disorder but who, thanks to a stem cell/gene therapy treatment, is now healthy and leading a normal life.

Because of the pandemic everything was virtual, but it was no less compelling for that. We interviewed each of the patients or patient advocates beforehand and those videos kicked off each session. Hearing, and seeing, the patients and patient advocates tell their stories set the scene for what followed. It meant that the research the scientists talked about took on added significance. We now had faces and names to highlight the importance of the work the scientists were doing. We had human stories. And that gave a sense of urgency to the work the researchers were doing.

But that wasn’t all. After all the video presentations each session ended with a “live” panel discussion. And again, the patients and patient advocates were a key part of that. Because when scientists talk about taking their work into a clinical trial they need to know if the way they are setting up the trial is going to work for the patients they’re hoping to recruit. You can have the best scientists, the most promising therapy, but if you don’t design a clinical trial in a way that makes it easy for patients to be part of it you won’t be able to recruit or retain the people you need to test the therapy.

Patient voices count. Patient stories count.

But more than anything, hearing and seeing the people we are trying to help reminds us why we do this work. It’s so easy to get caught up in the day to day business of our jobs, struggling to get an experiment to work, racing to get a grant application in before the deadline. Sometimes we get so caught up in the minutiae of work we lose sight of why we are doing it. Or who we are doing it for.

At CIRM we have a saying; come to work every day as if lives depend on you, because lives depend on you. Listening to the voices of patients, seeing their faces, hearing their stories, reminds us not to waste a moment. Because lives depend on all of us.

Here’s one of the interviews that was featured at the event. I do apologize in advance for the interviewer, he’s rubbish at his job.

Living proof science can find a cure

Like many kids, let’s face it, many adults too, Ronav “Ronnie” Kashyap is getting a little bored stuck inside all day during the coronavirus pandemic. This video, shot by his dad Pawash, shows Ronnie trying to amuse himself by pretending to be hard at work.

https://www.instagram.com/p/B_BSQaonFXb/

It’s a lovely moment. It’s also a moment that just a few years ago seemed almost impossible. That’s because Ronnie was born with severe combined immunodeficiency (SCID). SCID kids have no functioning immune system so even a simple infection, such as a cold, can be life-threatening.

Many of those hardest hit by COVID-19 have compromised immune systems. But try fighting the virus if you have no immune system at all. The odds would not be good.

Happily, we don’t have to imagine it because Ronnie is one of around 60 children who have undergone CIRM-supported stem cell/gene therapies that have helped repair their immune system.

In Ronnie’s case he was rushed to UC San Francisco shortly after his birth when a newborn screening test showed he had SCID. He spent the next several months there, in isolation with his parents, preparing for the test. Doctors took his own blood stem cells and, in the lab, corrected the genetic mutation that causes SCID. The cells were then re-infused into Ronnie where they created a new blood supply and repaired his immune system.

How good is his immune system today? Last year his parents, Upasana and Pawash, were concerned about taking Ronnie to a crowded shopping mall for fear he might catch a cold. Their doctor reassured them that he would be fine. So, they went. The doctor was right, Ronnie was fine. However, Upasana and Pawash both caught colds!

Just a few weeks ago Ronnie started pre-school. He loves it. He loves having other kids to play with and his parents love it because it helps him burn off some energy. But they also love it because it showed Ronnie is now leading a normal life, one where they don’t have to worry about everything he does, every person he comes into contact with.

Sounds a bit like how the rest of us are living right now doesn’t it. And the fears that Ronnie’s parents had, that even a casual contact with a friend, a family member or stranger, might prove life-threatening, are ones many of us are experiencing now.

When Ronnie was born he faced long odds. At the time there were only a handful of scientists working to find treatments for SCID. But they succeeded. Now, Ronnie, and all the other children who have been helped by this therapy are living proof that good science can overcome daunting odds to find treatments, and even cures, for the most life-threatening of conditions.

Today there are thousands, probably tens of thousands of scientists around the world searching for treatments and cures for COVID-19. And they will succeed.

Till then the rest of us will have to be like Ronnie. Stay at home, stay safe, and enjoy the luxury of being bored.

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)


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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.