John Zaia

Month of CIRM: Battling COVID-19

/ Kevin McCormack / Leave a comment

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the people of California approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future.

Dr. John Zaia, City of Hope stem cell researcher

The news that effective vaccines have been developed to help fight COVID-19 was a truly bright spot at the end of a very dark year. But it will be months, in some countries years, before we have enough vaccines to protect everyone. That’s why it’s so important to keep pushing for more effective ways to help people who get infected with the virus.

One of those ways is in a clinical study that CIRM is funding with City of Hope’s Dr. John Zaia. Dr. Zaia and his team, in partnership with the Translational Genomics Research Institute (TGen) in Flagstaff, Arizona, are using something called convalescent plasma to try and help people who have contracted the virus. Here’s the website they have created for the study.

Plasma is a part of our blood that carries proteins, called antibodies, that help defend our bodies against viral infections. When a patient recovers from COVID-19, their blood plasma contains antibodies against the virus. The hope is that those antibodies can now be used as a potential treatment for COVID-19 to help people who are newly infected. 

To carry out the study they are using clinical trial sites around California, including some of the CIRM Alpha Stem Cell Network clinics.

For the study to succeed they’ll first need people who have recovered from the virus to donate blood. That’s particularly appropriate in January because this is National Volunteer Blood Donor Month.

The team has three elements to their approach:

  • A rapid-response screening program to screen potential COVID-19 convalescent plasma donors, particularly in underserved communities.
  • A laboratory center that can analyze the anti-SARS-CoV-2 antibodies properties in COVID-19 convalescent plasma.
  • An analysis of the clinical course of the disease in COVID-19 patients to identify whether antibody properties correlate with clinical benefit of COVID-19 convalescent plasma.

There’s reason to believe this approach might work. A study published this week in the New England Journal of Medicine, found that blood plasma from people who have recovered from COVID-19 can help older adults and prevent them from getting seriously ill with the virus if they get the plasma within a few days of becoming infected.

We are used to thinking of blood donations as being used to help people after surgery or who have been in an accident. In this study the donations serve another purpose, but one that is no less important. The World Health Organization describes blood as “the most precious gift that anyone can give to another person — the gift of life. A decision to donate your blood can save a life, or even several if your blood is separated into its components — red cells, platelets and plasma.”

That plasma could help in developing more effective treatments against the virus. Because until we have enough vaccines for everyone, we are still going to need as much help as we can get in fighting COVID-19. The recent surge in cases throughout the US and Europe are a reminder that this virus is far from under control. We have already lost far too many people. So, if you have recently recovered from the virus, or know someone who has, consider donating blood to this study. It could prove to be a lifesaver.

For more information about the study and how you can be part of it, click here.

Want to help us solve a mystery?

/ Kevin McCormack / 1 Comment
Patient that has recovered from Covid-19 donating blood plasma. Photo courtesy Science Photo

Convalescent plasma has been in the news a lot lately as a potential treatment for people infected with the coronavirus. In August the US Food and Drug Administration (FDA) granted emergency use authorization (EUA) to use these products based on preliminary data that suggested it might help people battling COVID. But there are still a lot of unanswered questions about this approach.

And that’s where you come in.

Plasma is a component of blood that carries proteins called antibodies that are usually involved in defending our bodies against viral infections.  We also know that blood plasma from patients that have recovered from COVID-19, referred to as convalescent plasma, contain antibodies against the virus that can be used as a potential treatment for COVID-19. 

That’s the theory, but the reality is that there are still a lot we don’t know, basic questions such as does it really work, how does it work, does it work for everyone or just some patients? A clinical  grant includes testing the plasma in COVID-19 Positive patients that CIRM is funding with City of Hope, UC Irvine and Translational Genomics Research Institute (TGen) hopes to answer those questions. 

The first step is getting the plasma from people who have recovered from COVID and then testing it to make sure it’s safe and to identify what blood type it is, so you can match that blood type with the person receiving it.

But plasma doesn’t contain just one kind of antibody, there are many antibodies and each one works in a slightly different way. For example, two antibodies, IGM and IGG, target in on the spike protein on the coronavirus. The goal is to block that spike and prevent the virus from spreading throughout the body. IGM has up to 10 ‘arms’ and so has the potential to bind multiple copies of the spike, whereas IGG has only 2 arms, but lasts longer. Both IGM and IGG also come in many different flavors, allowing them to bind to many different parts of the spike, some being more protective than others.

That’s one of the things that this trial is trying to find out. And you can help them do that. The trial needs volunteers, volunteers to donate the plasma and volunteers to try the therapy.

The team is evaluating changes that occur before and after plasma treatment.  Many recipients have no immediate response, a few get dramatically better, and some continue to have symptoms long after discharge from the hospital.  These so-called “long-haulers” can have debilitating problems, months after becoming infected. The study hopes to evaluate these variable responses to plasma treatment.

But more people are needed if we are to truly understand what works best. We need people who are newly infected, those being treated with plasma, and those that have recovered from the virus.

We are particularly interested in recruiting people from the Black and Latinx communities, groups that are often underserved when it comes to access to medical care.

The team has created a website to make it easy to find out more about the clinical trial, and to see if you are a good candidate to be part of it, either as a donor or recipient.

Lives are at stake and time is short so join us, help us find answers to the most pressing medical issue of our times. It’s a chance to do something that might benefit your family, your friends and your community.

Meet the people who are changing the future

/ Kevin McCormack / 2 Comments
Kristin MacDonald

Every so often you hear a story and your first reaction is “oh, I have to share this with someone, anyone, everyone.” That’s what happened to me the other day.

I was talking with Kristin MacDonald, an amazing woman, a fierce patient advocate and someone who took part in a CIRM-funded clinical trial to treat retinitis pigmentosa (RP). The disease had destroyed Kristin’s vision and she was hoping the therapy, pioneered by jCyte, would help her. Kristin, being a bit of a pioneer herself, was the first person to test the therapy in the U.S.

Anyway, Kristin was doing a Zoom presentation and wanted to look her best so she asked a friend to come over and do her hair and makeup. The woman she asked, was Rosie Barrero, another patient in that RP clinical trial. Not so very long ago Rosie was legally blind. Now, here she was helping do her friend’s hair and makeup. And doing it beautifully too.

That’s when you know the treatment works. At least for Rosie.

There are many other stories to be heard – from patients and patient advocates, from researchers who develop therapies to the doctors who deliver them. – at our CIRM 2020 Grantee Meeting on next Monday September 14th Tuesday & September 15th.

It’s two full days of presentations and discussions on everything from heart disease and cancer, to COVID-19, Alzheimer’s, Parkinson’s and spina bifida. Here’s a link to the Eventbrite page where you can find out more about the event and also register to be part of it.

Like pretty much everything these days it’s a virtual event so you’ll be able to join in from the comfort of your kitchen, living room, even the backyard.

And it’s free!

You can join us for all two days or just one session on one day. The choice is yours. And feel free to tell your friends or anyone else you think might be interested.

We hope to see you there.

Scientists Engineer Stem Cells to Fight HIV

/ Kevin McCormack / Leave a comment
Image of the virus that causes AIDS – courtesy NIH

If that headline seems familiar it should. It came from an article in MIT Technology Review back in 2009. There have been many other headlines since then, all on the same subject, and yet here we are, in 2020, and still no cure for HIV/AIDS. So what’s the problem, what’s holding us back?

First, the virus is incredibly tough and wily. It is constantly mutating so trying to target it is like playing a game of ‘whack a mole’. Secondly not only can the virus evade our immune system, it actually hijacks it and uses it to help spread itself throughout the body. Even new generations of anti-HIV medications, which are effective at controlling the virus, can’t eradicate it. But now researchers are using new tools to try and overcome those obstacles and tame the virus once and for all.

Dr. Scott Kitchen: Photo David Geffen School of Medicine, UCLA

UCLA researchers Scott Kitchen and Irvin Chen have been awarded $13.65 million by the National Institutes of Health (NIH) to see if they can use the patient’s own immune system to fight back against HIV.

Dr. Irvin Chen: Photo UCLA

Dr. Kitchen and Dr. Chen take the patient’s own blood-forming stem cells and then, in the lab, they genetically engineer them to carry proteins called chimeric antigen receptors or CARs. Once these blood cells are transplanted back into the body, they combine with the patient’s own immune system T cells (CAR T). These T cells now have a newly enhanced ability to target and destroy HIV.

That’s the theory anyway. Lots of research in the lab shows it can work. For example, the UCLA team recently showed that these engineered CAR T cells not only destroyed HIV-infected cells but also lived for more than two years. Now the team at UCLA want to take the lessons learned in the lab and apply them to people.

In a news release Dr. Kitchen says the NIH grant will give them a terrific opportunity to do that: “The overarching goal of our proposed studies is to identify a new gene therapy strategy to safely and effectively modify a patient’s own stem cells to resist HIV infection and simultaneously enhance their ability to recognize and destroy infected cells in the body in hopes of curing HIV infection. It is a huge boost to our efforts at UCLA and elsewhere to find a creative strategy to defeat HIV.”

By the way, CIRM helped get this work off the ground with an early-stage grant. That enabled Dr. Kitchen and his team to get the data they needed to be able to apply to the NIH for this funding. It’s a great example of how we can kick-start projects that no one else is funding. You can read a blog about that early stage research here.

CIRM has already funded three clinical trials targeting HIV/AIDS. Two of these are still active; Dr. Mehrdad Abedi at UC Davis and Dr. John Zaia at City of Hope.

California gets first royalty check from Stem Cell Agency investments

/ Kevin McCormack / Leave a comment

COH image

CIRM recently shared in a little piece of history. The first royalty check, based on CIRM’s investment in stem cell research, was sent to the California State Treasurer’s office from City of Hope. It’s the first of what we hope will be many such checks, helping repay, not just the investment the state made in the field, but also the trust the voters of California showed when they created CIRM.

The check, for $190,345.87, was for a grant we gave City of Hope back in 2012 to develop a therapy for glioblastoma, one of the deadliest forms of brain cancer. That has led to two clinical trials and a number of offshoot inventions that were subsequently licensed to a company called Mustang Bio.

Christine Brown, who is now the principal investigator on the project, is quoted in a front page article in the San Francisco Chronicle, on the significance of the check for California:

“This is an initial payment for the recognition of the potential of this therapy. If it’s ultimately approved by the FDA as a commercial product, this could be a continued revenue source.”

In the same article, John Zaia, Director of the City of Hope Alpha Stem Cell Clinic, says this also reflects the unique nature of CIRM:

“I think this illustrates that a state agency can actually fund research in the private community and get a return on its investment. It’s something that’s not done in general by other funding agencies such as the National Institutes of Health, and this is a proof of concept that it can work.”

Maria Millan, CIRM’s President & CEO, says the amount of the payment is not the most significant part of this milestone – after all CIRM has invested more than $2.5 billion in stem cell research since 2004. She says the fact that we are starting to see a return on the investment is important and reflects some of the many benefits CIRM brings to the state.

“It’s a part of the entire picture of the return to California. In terms of what it means to the health of Californians, and access to these transformative treatments, as well as the fact that we are growing an industry.”

 

Inspiring the next generation of stem cell scientists

/ Karen Ring / Leave a comment

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SPARK students at the 2017 Annual Meeting at the City of Hope.

“The technological breakthroughs that will be happening over the next few years – it’s your generation of scientists that will make this happen.”

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John Zaia

Dr. John Zaia, the Director of City of Hope’s Center for Gene Therapy, directed these words to a group of 55 talented high school students attending the 2017 CIRM SPARK meeting.

SPARK stands for Summer Program to Accelerate Regenerative Medicine Knowledge. Students in the program spend their summer tackling difficult stem cell research projects in the lab, attending scientific workshops and lectures, and participated in patient engagement activities.

At the end of the summer, SPARK students from seven different programs at institutions and universities across California attend the annual SPARK meeting. At this gathering, students present their research to researchers and their families. They also hear about the progress in developing stem cell therapies from scientists and doctors and about exciting career paths in science and STEM fields from SPARK alumni.

The program is an excellent way for high school students to get their “research feet” wet. They are trained in basic lab and stem cell techniques and are assigned to a mentor who guides them through their research project.

Many of the students who participate in our SPARK programs go on to prestigious colleges to pursue degrees in science, medicine, and engineering. You can read some of these stories on our blog here and here.

At CIRM, we are invested in educating the next generation of stem cell scientists. Our Vice-Chair of the CIRM Board, Sen. Art Torres, said it perfectly at this year’s SPARK meeting:

“I just want to thank you for being part of this program. We are very proud of each and every one of you and we expect great things in the future.”

Check out this short video, produced by City of Hope, which features highlights from our 2017 SPARK meeting at the City of Hope. As you will see, this program is not only fun, but is a one-in-a-lifetime experience.

If you’re interested in learning more about our SPARK program or applying to be a SPARK intern, visit our website for more information. SPARK programs typically accept applications in December or early in the year. Each program has its own eligibility requirements and application process and you can find out that information on the individual SPARK program websites listed on our CIRM SPARK webpage.

Patients are the Heroes at the CIRM Alpha Stem Cell Clinics Symposium

/ Kevin McCormack / Leave a comment

Alpha Cat and Sandra.jpg

UCSD’s Catriona Jamieson and patient advocate Sandra Dillon at the CIRM Alpha Clinic Network Symposium

Sometimes, when you take a moment to stand back and look at what you have accomplished, you can surprise yourself at how far you have come, and how much you have done in a short space of time.

Take the CIRM Alpha Stem Cell Clinics Network for example. In the 18 months since our Board invested $24 million to kick start the first three Alpha Clinics the Network has signed up 21 clinical trials. That’s no small achievement. But as far as the Alpha Clinics Network team is concerned, that’s just a start.

Alpha clinic table

Last week UC San Diego hosted the Second Annual CIRM Alpha Stem Cell Clinics Network Symposium. The gathering of scientists, medical staff and patient advocates spent a little time talking about the past, about what has been achieved so far, but most of the time was devoted to looking to the future, planning where they want to go and how they are going to get there.

The Network’s goal is to now dramatically increase the number of high quality stem cell clinical trials it is running, to make it even easier for companies and researchers looking for a site to carry out their trial, and to make it even easier for patients looking to sign up for one.

Alpha clinic panel

Panel at symposium: L to R: David Higgins, CIRM Board; David Parry, GSK; Catriona Jamieson, UCSD: John Zaia, City of Hope; John Adams, UCLA

For companies, the lure of having three Alpha Clinics (UC San Diego, City of Hope and the combined team of UCLA/UC Irvine) packed with skilled, experienced staff that specialize in delivering stem cell therapies is a big draw. (By the way, if you know anyone looking for funding for a clinical trial send them here).

The Alpha Clinic teams not only know how to deliver the therapies, they also know how to deliver patients. They spend a lot of time working with patients and patient advocates on the best ways to recruit people for trials, and the best way to design those trials so that they are as easy as possible for patients to take part in.

This attention to making it as good an experience for patients as possible starts from the very first time that a patient calls the clinics to find out if they are eligible for a trial. If there is no trial that is appropriate for that particular patient, the staff try to find an alternative trial at another location that might work.

Making sure it’s a good fit

If the Network does have a trial that meets the needs of the patient, then they begin the conversation to find out if the patient is eligible to apply. The goal of this part of the process is not simply to try and fill up available slots but to make sure that the patient is both a good match for the proposed therapy and that they also completely understand what’s involved in getting that therapy. For example, they need to understand if the trial involves staying overnight or several nights in the hospital, or if there are things they need to do ahead of time to prepare.

For the clinics themselves, one of the biggest challenges is insurance coverage. While the trial itself may be free, the patient may need to have some tests ahead of the treatment, to make sure they don’t have any underlying problems that could put their health at risk. The clinics need to know if the patient’s insurance will cover the cost of those tests and if they don’t what their options are. For a rare disease, where it’s challenging to find enough patients to produce meaningful results, these kinds of problems can jeopardize the whole trial.

The Alpha Clinics Network is working hard to develop answers to all of those problems, to create systems that make it as easy as possible to get a clinical trial up and running, and to recruit and keep patients in that trial.

Challenges to overcome

Part of the challenge is that many of these trials are for first-in-human therapies, meaning no one has ever tried this in a person before. That means the doctors, nurses and all the support staff in these clinics need to be specially trained in dealing with an entirely new way of treating people, with an entirely new class of therapies. And this isn’t just about technical skills. They also need to be good at communication, helping the patients understand everything that is happening or about to happen.

In a state like California, one of the most diverse places on earth, that’s no easy challenge. According to a UCLA study there are more than 220 languages spoken in LA County alone. Coping with that level of linguistic, cultural, and religious diversity is a challenge that the Alpha Clinics are working hard to meet.

Listening to patients

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Patient advocates were also an important voice at the symposium, talking about their experiences in clinical trials and how they have helped change their lives, and how they have, in some cases, saved their lives. But they also had some thoughts on how the researchers can do an even better job. That is the subject for a future blog.

While everyone acknowledged the challenges the CIRM Alpha Clinics face, they also celebrated what they have accomplished so far, and looked forward to the future. And the symposium was a chance to remind all of us that the reason we are in this is to help patients battling deadly diseases and disorders. So it was fitting that Thomas Kipps, the Deputy Director of Research at the UCSD Moore’s Cancer Center, took the opportunity to thank those who are not just the focus of this work, but also the heroes.

Kipps

Thomas Kipps: Photo courtesy Patient Power

“Clinical trials involve a very important skill set. You have to first and foremost put the patient first in any clinical trial. I think we cannot ignore the fact that these are human beings that are brave souls that have gone forward. These are the heroes who are going out and forging new territory.”

The search for a cure: how stem cells could eradicate the AIDS virus

/ Kevin McCormack / 1 Comment

It’s hard to overstate just how devastating the AIDS crisis was at its peak in the U.S. – and still is today in many parts of the world. In 1995 almost 51,000 Americans died from the disease, the numbers of new cases were at almost record highs, and there were few effective therapies against the virus.

HIV/AIDS medications

HIV/AIDS medications

Today that picture is very different. New medications and combination therapies have helped reduce the death rate, in some cases turning HIV into a chronic rather than fatal condition. But even now there is no cure.

That’s why the news that the Food and Drug Administration (FDA) has approved a clinical trial, that we are funding, aimed at eradicating HIV in the body, was so welcome. This could be an important step towards the Holy Grail of AIDS therapies, curing the disease.

The project is headed by Dr. John Zaia at City of Hope near Los Angeles. The team, with researchers from Keck Medicine of the University of Southern California (USC) and Sangamo BioSciences, plans on using an individual’s own stem cells to beat the virus.  They will remove some blood stem cells from HIV-infected individuals, then treat them with zinc finger nucleases (ZFNs), a kind of molecular scissors, snipping off a protein the AIDS virus needs to infect those cells.

It’s hoped the re-engineered stem cells, when returned to the body, will help create a new blood and immune system that is resistant to the virus. And if the virus can’t infect any new immune cells it could, theoretically, die off. Check out the video we produced a few years back about the project:

Studies in the lab show this approach holds a lot of promise. In a news release announcing the start of the clinical trial, Dr. Zaia said now it’s time to see if it will work in people:

“While we have a number of drugs that are effective in holding HIV at bay, we have nothing that cures it. In addition, for many patients, these medications come with significant long-term problems so there is a real need for a therapy that can help eradicate the virus from a patient completely. That is where our work is focused.”

Like all Phase 1 trials this one is focused on making sure this approach is safe for people, and identifying what, if any, side-effects there are from the treatment. The first group of patients to be treated consists of people with HIV/AIDS who have not responded well to the existing medications.

This is the second trial that CIRM is funding focused on curing HIV/AIDS. Our first, involving the company Calimmune, began its human clinical trial in July 2013. You can read more about that work here.

We know that the road to a cure will not be simple or straightforward. There have been too many false claims of cures or miracle therapies over the years for any of us to want to fall victim to hope and hype. It may even be that the most realistic goal for these approaches is what is called a “functional cure”, one that doesn’t eliminate the virus completely but does eliminate the need to take antiretroviral pills every day.

But when compared to the dark days of 1995, a functional cure is a world away from certain death.