Raising awareness about Rare Disease Day

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One of the goals we set ourselves at CIRM in our 2016 Strategic Plan was to fund 50 new clinical trials over the next five years, including ten rare or orphan diseases. Since then we have funded 13 new clinical trials including four targeting rare diseases (retinitis pigmentosa, severe combined immunodeficiency, ALS or Lou Gehrig’s disease, and Duchenne’s Muscular Dystrophy). It’s a good start but clearly, with almost 7,000 rare diseases, this is just the tip of the iceberg. There is still so much work to do.

And all around the world people are doing that work. Today we have asked Emily Walsh, the Community Outreach Director at the Mesothelioma Cancer Alliance,  to write about the efforts underway to raise awareness about rare diseases, and to raise funds for research to develop new treatments for them.

“February 28th marks the annual worldwide event for Rare Disease Day. This is a day dedicated to raising awareness for rare diseases that affect people all over the world. The campaign works to target the general public as well as policy makers in hopes of bringing attention to diseases that receive little attention and funding. For the year 2017 it was decided that the focus would fall on “research,” with the slogan, “With research, possibilities are limitless.”

Getting involved for Rare Disease Day means taking this message and spreading it far and wide. Awareness for rare diseases is extremely important, especially among researchers, universities, students, companies, policy makers, and clinicians. It has long been known that the best advocates for rare diseases are the patients themselves. They use their specific perspectives to raise their voice, share their story, and shed light on the areas where additional funding and research are most necessary.

To see how you can help support the Rare Disease Day efforts this year, click here.

Groups like the Mesothelioma Cancer Alliance and the Mesothelioma Group are adding their voices to the cause to raise awareness about mesothelioma cancer, a rare form of cancer caused by exposure and inhalation of airborne asbestos fibers

Rare diseases affect 300 million people worldwide, but only 5% of them have an FDA approved treatment or cure. Malignant mesothelioma is among the 95 percent that doesn’t have a treatment or cure.

Asbestos has been used throughout history in building materials because of its fire retardant properties. Having a home with asbestos insulation, ceiling tiles, and roof shingles meant that the house was safer. However, it was found that once asbestos crumbled and became powder-like, the tiny fibers could become airborne and be inhaled and lodge themselves in lung tissue causing mesothelioma. The late stage discovery of mesothelioma is often what causes it to have such a high mortality rate. Symptoms can have a very sudden onset, even though the person may have been exposed decades prior.

Right now, treatment for mesothelioma includes the usual combination of chemotherapy, radiation, and surgery, but researchers are looking at other approaches to see if they can be more effective or can help in conjunction with the standard methods. For example one drug, Defactinib, has shown some promise in inhibiting the growth and spread of cancer stem cells – these are stem cells that can evade chemotherapy and cause patients to relapse.”

Some people might ask why spend limited resources on something that affects so few people. But the lessons we learn in developing treatments for a rare disease can often lead us to treatments for diseases that affect many millions of people.

But numbers aside, there is no hierarchy of need, no scale to say the suffering of people with Huntington’s disease is any greater or less than that of people with Alzheimer’s. We are not in the business of making value judgements about who has the greatest need. We are in the business of accelerating treatments to patients with unmet medical needs. And those suffering from rare disease are very clearly  people in need.

 


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The power of the patient’s voice: how advocates shape clinical trials and give hope to those battling deadly diseases

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The Stack family: L to R Alex, Natalie, Nancy & Jeff

Tennis great Martina Navratilova was once being interviewed about what made her such a great competitor and she said it was all down to commitment. When pressed she said “the difference between involvement and commitment is like ham and eggs; the chicken is involved but the pig is committed.”

That’s how I feel about the important role that patients and patient advocates play in the work that we do at CIRM. Those of us who work here are involved. The patients and patient advocates are committed. This isn’t just their life’s work;  it’s their life.

I was reminded of that last week when I had the privilege of talking with Nancy Stack, the Patient Representative on a Clinical Advisory Panel (CAP) we have created for a program to treat cystinosis. She has an amazing story to tell. But before we get to that I have to do a little explaining.

Cystinosis is a rare disease, affecting maybe only 2,000 people worldwide, that usually strikes children before they are two years old and can lead to end stage kidney failure before their tenth birthday. Current treatments are limited, which is why the average life expectancy for someone with this is only around 27 years.

When we fund a project that is already in, or hoping to be in, a clinical trial we create a CAP to help assist the team behind the research. The CAP consists of a CIRM Science Officer, an independent scientific expert in this case for cystinosis, and a Patient Representative.

The patient’s voice

The Patient Representative’s role is vital because they can help the researchers understand the needs of the patient and take those needs into account when designing the trial. In the past, many researchers had little contact with patients and so designed the trial around their own needs. The patients had to fit into that model. We think it should be the other way around; that the model should fit the patients. The Patient Representatives help us make that happen.

Nancy Stack did just that. At the first meeting of the CAP she showed up with a list of 38 questions that she and other families with cystinosis had come up with for the researchers. They went from the blunt – “Will I die from the treatment” – to the practical –  “How will children/teens keep up with school during the process?” – and included a series of questions from a 12-year old girl with the disease – “Will I lose my hair because I’ve been growing it out for a long time? Will I feel sick? Will it hurt?”

Nancy says the questions are not meant to challenge the researcher, in this case U.C. San Diego’s Stephanie Cherqui, but to ensure that if the trial is given the go-ahead by the US Food and Drug Administration (FDA) that every patient who signs up for it knows exactly what they are getting into. That’s particularly important because many of those could be children or teenagers.

Fully informed

“As parents we know the science is great and is advancing, but we have real people who are going to go through this treatment so we have a responsibility to know what will it mean to them. Patients know they could die of the disease and so this research has real world implications for them.”

“I think without this, without allowing the patients voice to be heard, you would have a hard time recruiting patients for this kind of clinical trial.”

Nancy says not only was Dr. Cherqui not surprised by the questions, she welcomed them. Dr. Cherqui has been supported and funded by the Cystinosis Research Foundation for years and Nancy says she regards the patients and patient advocates as partners in this journey:

“She knows we are not challenging her, we’re supporting her and helping her cover every aspect of the research to help make it work.”

Nancy became committed to finding a cure for cystinosis when her daughter, Natalie, was diagnosed with the condition when she was just 7 months old. The family were handed a pamphlet titled “What to do when your child has a terminal disease” and told there was no cure.

Birthday wish

In 2003, on the eve of her 12th birthday, Nancy asked Natalie what her wish was for her birthday. She wrote on a napkin “to have my disease go away forever.” The average life expectancy for people with cystinosis at that point was 18. Nancy told her husband “We have to do something.”

They launched the Cystinosis Research Foundation and a few weeks later they held their first fundraiser. That first year they raised $427,000, an impressive amount for such a rare disease. Last year they raised $4.94 million. Every penny of that $4.94 million goes towards research, making them the largest funders of cystinosis research in the world.

“We learned that for there to be hope there has to be research, and to do research we needed to raise funds. Without that we knew our children would not survive this disease.”

Natalie is now 26, a graduate of Georgetown and USC, and about to embark on a career in social work. Nancy knows many others are not so fortunate:

“Every year we lose some of our adults, even some of our teens, and that is unbelievably hard. Those other children, wherever they may live, they are my children too. We are all connected to each other and that’s what motivates me every day. Having a child with this disease means that time is running out and there must be a commitment to work hard every day to find a cure, and never giving up until you do.”

That passion for the cause, that compassion for others and determination to help others makes the Patient Representative on the CAP so important. They are a reminder that we all need to work as hard as we can, as fast as we can, and do everything we can to help these trials succeed.

And we are committed to doing that.


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How a Soviet space craft proved an inspiration for CIRM’s latest Board member

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George Blumenthal’s life changed on October 4, 1957. That’s the day the Soviet Union launched Sputnik, the world’s first artificial earth satellite. The beach ball-sized satellite marked the start of the space race between the US and the USSR. It also marked the start of Blumenthal’s fascination with science and space.

Fast forward almost 60 years and Dr. Blumenthal, now a world-renowned professor of astronomy and astrophysics and the Chancellor of U.C. Santa Cruz, has been named as the newest member of the CIRM governing Board.

California Lt. Governor Gavin Newsom made the appointment calling Dr. Blumenthal a world-class scientist and forward-looking administrator:

“As a Regent of the University of California, I have been impressed by his deep commitment to expanding educational opportunity for all California students and enhancing research opportunities. I am confident the Chancellor’s vision and leadership will be of immense benefit to the CIRM Board.”

In a news release Dr. Blumenthal said he is looking forward to being part of CIRM:

“The California Institute for Regenerative Medicine is doing outstanding work, and I am delighted to join the Board. CIRM support has advanced stem cell research at UC Santa Cruz and across the state. Public support for this work remains strong, and I look forward to playing a role in securing the future of the institute.”

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Sputnik

But getting back to Sputnik for a moment. In an article in Valley Vision, the newsletter for Joint Venture Silicon Valley, Dr. Blumenthal said the launch of Sputnik helped fuel his interest in science in general and space in particular.

“Sputnik had a profound effect on American science and it certainly played a part in my interest in space and physics all through high school, college and graduate school,” says Blumenthal. “I intended to become a particle physicist, but after a year in grad school I became more interested in space and astronomy, so I changed from studying the smallest things in the universe to the biggest, like galaxies.”

Dr. Blumenthal became the first in his family to graduate from college. He then went on to enjoy a successful career as a professor of astronomy and astrophysics. His research helped deepen our understanding of galaxies and the cosmos, including the role that dark matter plays in the formation of the structure of the universe. He became the chair of the California Association for Research in Astronomy (CARA), which manages the W. M. Keck Observatory near the summit of Mauna Kea in Hawaii. He also co-authored two of the leading astronomy textbooks, 21st Century Astronomy and Understanding our Universe.

Blumenthal joined the faculty of UC Santa Cruz in 1972 and was named chancellor in 2007. Throughout his career he has been a champion of diversity both at UCSC, where he created the Chancellor’s Advisory Council on Diversity, and throughout the U.C. system, where he served as a member of the Regents’ Study Group on Diversity.

Jonathan Thomas, Chair of the CIRM Board, welcomed Dr. Blumenthal, saying:

“We are honored to have someone with Dr. Blumenthal’s experience and expertise join the Board. As Chancellor at UCSC he has demonstrated a clear commitment to advancing world-class research and earned a reputation as a bold and visionary leader. We look forward to seeing those qualities in action to help advance CIRM’s mission.”

At CIRM we are shooting for the stars, aiming as high as we can to help accelerate stem cell treatements to patients with unmet medical needs. It will be nice having Dr. Blumenthal on Board to help guide us.

Stem Cell Profiles in Courage: Brenden Whittaker

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Brenden Whittaker: Photo Colin McGuire

It’s not often you meet someone who says one of their favorite things in the world is mowing the lawn. But then, there aren’t many people in the world like Brenden Whittaker. In fact, as of this writing, he may be unique.

Brenden was born with severe chronic granulomatous disease (x-CGD), a rare genetic disorder that left him with an impaired immune system that was vulnerable to repeated bacterial and fungal infections. Over 22 years Brenden was in and out of the hospital hundreds of times, he almost died a couple of times, and lost parts of his lungs and liver.

Then he became the first person to take part in a clinical trial to treat x-CGD. UCLA researcher Don Kohn had developed a technique that removed Brenden’s blood stem cells, genetically re-engineered them to correct the mutation that caused the disease, and then returned those stem cells to Brenden. Over time they created a new blood system, and restored Brenden’s immune system.

He was cured.

We profiled Brenden for our 2016 Annual Report. Here’s an extended version of the interview we did with him, talking about his life before and after he was cured.

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Brenden with a CIRM Game Ball – signed by everyone at CIRM

Brenden’s story:

I still think about it, my disease, every few days or so and it’s weird because in the past I was sick so often; before this year, I was sick consistently for about 5 years and going to doctor’s appointments 2 or 3 times a week and being in the hospital. So, it’s weird having a cough and not having to be rushed to the ER, not having to call someone every time the smallest thing pops up, and not having to worry about what it means.

It’s been good but it’s been weird to not have to do that.  It’s a nice problem to have.

What are you doing now that you didn’t do before?

Cutting the grass is something I couldn’t do before, that I’ve taken up now. Most people look at me as if I’m crazy when I say it, but I love cutting grass, and I wasn’t able to do it for 22 years of my life.

People will complain about having to pick up after their dog goes to the bathroom and now I can follow my dog outside and can pick up after her. It really is just the little things that people don’t think of. I find enjoyment in the small things, things I couldn’t do before but now I can and not have to worry about them.

The future

I was in the boy scouts growing up so I love camping, building fires, just being outdoors. I hiked on the Appalachian Trail. Now I’ll be able to do more of that.

I have a part time job at a golf course and I’m actually getting ready to go back to school full time in January. I want to get into pre-med, go to medical school and become a doctor. All the experience I’ve had has just made me more interested in being a doctor, I just want to be in a position where I can help people going through similar things, and going through all this just made me more interested in it.

Before the last few months I couldn’t schedule my work more than a week in advance because I didn’t know if I was going to be in the hospital or what was going on. Now my boss jokes that I’m giving him plans for the next month or two. It’s amazing how far ahead you can plan when you aren’t worried about being sick or having to go to the hospital.

I’d love to do some traveling. Right now most of my traveling consists of going to and from Boston (for medical check-ups), but I would love to go to Europe, go through France and Italy. That would be a real cool trip. I don’t need to see everything in the world but just going to other countries, seeing cities like London, Paris and Rome, seeing how people live in other cultures, that would be great.

Advice for others

I do think about the fact that when I was born one in a million kids were diagnosed with this disease and there weren’t any treatments. Many people only lived a few years. But to be diagnosed now you can have a normal life. That’s something all on its own. It’s almost impossible for me to fathom it’s happening, after all the years and doctor’s appointments and illnesses.

So, for people going through anything like this, I’d say just don’t give up. There are new advances being made every day and you have to keep fighting and keep getting through it, and some day it will all work out.


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Stem Cells Profile in Courage: Pat Furlong, Patient Advocate

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Pat Furlong: Photo by Colin McGuire – http://www.colinmcguire.com

One of the true joys for me in helping put together this year’s Annual Report was getting to know the patients and patient advocates that we profiled in the report. These are some extraordinary individuals and the short profiles we posted only touch the surface of just how extraordinary.

So, over the next few weeks we are going to feature four of these people at greater length, allowing them, in their own words, to talk about what makes them tic, and how they keep going in the face of what is often heartbreak and tragedy.

We begin with Pat Furlong, a Patient Advocate and the Founding President and CEO of Parent Project Muscular Dystrophy (PPMD), the largest nonprofit organization in the United States solely focused on Duchenne muscular dystrophy (DMD).

DMD is the most common fatal, genetic childhood disorder, which affects approximately 1 out of every 3,500 boys each year worldwide. It’s a progressive muscle disorder that leads to loss of muscle function, meaning you lose your ability to walk, to use your arms, and ultimately to breathe. And because the heart is a muscle, that is often seriously affected. There is no cure, and treatment options are limited. At the time her sons were diagnosed life expectancy was in the teens.

Pat’s story:

“When my sons, Chris and Pat were diagnosed with DMD, at the ages of 4 and 6, there was nothing available for them. Doctors cared about them but they didn’t have the tools they needed, or the National Institutes of Health the money it needed to do research.

Doctors were faced with diagnosing a disease and saying “there’s nothing we can do”. And then parents like me, coming to them hearing there was nothing they could do, no hope, no help. When your son is diagnosed with something like this you are told go home and love them.

When I asked questions, I was often ignored or dismissed by some doctors.

When my sons were diagnosed with DMD I would drop them off at school and go walking and that would help me deal with the anger.

For me staying in this is to be able to say to Chris and Pat in the universe, when you were here I tried my very best and when you were gone I continued to try my best so that others would have advantages that you didn’t receive.

I haven’t stood back and said I can’t go on.

The family is all scarred, we all suffered this loss. It’s much more apparent when we are together, there are empty chairs, emptiness. If we go to a family gathering we wish Chris and Pat were here, could be married. Now there’s my husband and our two daughters. We have a granddaughter, who is wonderful, but still we are incomplete and we will live with that forever.

I am trained as a nurse and I find DMD equal parts fascinating disease, heartbreaking and painful. I try to emphasize the fascinating so I can keep going. There are frustrations; lack of money, the slow process of regulatory approval, but I have an incredible team of very smart people and we are passionate about change so that helps keep us going.

Your only interest can’t be DMD, it can’t be. For me it’s certainly a priority, but it’s not my only interest. I love to go to an art museum and see how creative people work. I love Cirque du Soleil because they do things with their muscles I can’t imagine. Going outside and seeing these things makes the world better.

I am interested in the expression of art, to see how people dress, to see how people are creative, I love creativity, I think the human spirit is pretty amazing and the creativity around it. I think we are all pretty amazing but sometimes we don’t say it enough.

I recently saw a woman on the subway with a pair of tennis shoes that said “you are beautiful” and people around her were looking at her shoes and smiling, just because of those shoes. We forget to interact, and that was such a simple way of doing that.

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I relax by doing yoga, 90-minute hot yoga, as often as I can. I’ve also done a number of half marathons, but I’m more a walker than a runner. I find getting outside or hot yoga makes me concentrate on what I’m doing so that I can’t think of anything else. I can put it down and think about nothing and whisper prayers to my sons and say am I doing the right thing, is there something I should be doing differently? It’s my time to think about them and meditate about what they think would be important.

You need to give your mind time to cope, so it’s putting your phone down and your computer away. It’s getting rid of those interruptions. To put the phone, the computer down and get in a hot room and do yoga, or run around outside, to look at a tree and think about the changing season, the universe, the sun. It’s an incredible break for the brain to be able to rest.

I think the disease has made us kinder people and more thoughtful. When Chris died, we found a notebook he kept. In it was written “the meaning of life is a life of meaning”. I think that’s where we have all landed, what we all strive for, a life of meaning.

 

 

 

California’s stem cell agency rounds up the year with two more big hits

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CIRM Board meeting with  Jake Javier, CIRM Chair Jonathan Thomas, Vice Chair Sen. Art Torres (Ret.) and President/CEO Randy Mills

It’s traditional to end the year with a look back at what you hoped to accomplish and an assessment of what you did. By that standard 2016 has been a pretty good year for us at CIRM.

Yesterday our governing Board approved funding for two new clinical trials, one to help kidney transplant patients, the second to help people battling a disease that destroys vision. By itself that is a no small achievement. Anytime you can support potentially transformative research you are helping advance the field. But getting these two clinical trials over the start line means that CIRM has also met one of its big goals for the year; funding ten new clinical trials.

If you had asked us back in the summer, when we had funded only two clinical trials in 2016, we would have said that the chances of us reaching ten trials by the end of the year were about as good as a real estate developer winning the White House. And yet……..

Helping kidney transplant recipients

The Board awarded $6.65 million to researchers at Stanford University who are using a deceptively simple approach to help people who get a kidney transplant. Currently people who get a transplant have to take anti-rejection medications for the rest of their life to prevent their body rejecting the new organ. These powerful immunosuppressive medications are essential but also come with a cost; they increase the risk of cancer, infection and heart disease.

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CIRM President/CEO Randy Mills addresses the CIRM Board

The Stanford team will see if it can help transplant patients bypass the need for those drugs by injecting blood stem cells and T cells (which play an important role in the immune system) from the kidney donor into the kidney recipient. The hope is by using cells from the donor, you can help the recipient’s body more readily adjust to the new organ and reduce the likelihood the body’s immune system will attack it.

This would be no small feat. Every year around 17,000 kidney transplants take place in the US, and many people who get a donor kidney experience fevers, infections and other side effects as a result of taking the anti-rejection medications. This clinical trial is a potentially transformative approach that could help protect the integrity of the transplanted organ, and improve the quality of life for the kidney recipient.

Fighting blindness

The second trial approved for funding is one we are already very familiar with; Dr. Henry Klassen and jCyte’s work in treating retinitis pigmentosa (RP). This is a devastating disease that typically strikes before age 30 and slowly destroys a person’s vision. We’ve blogged about it here and here.

Dr. Klassen, a researcher at UC Irvine, has developed a method of injecting what are called retinal progenitor cells into the back of the eye. The hope is that these cells will repair and replace the cells damaged by RP. In a CIRM-funded Phase 1 clinical trial the method proved safe with no serious side effects, and some of the patients also reported improvements in their vision. This raised hopes that a Phase 2 clinical trial using a larger number of cells in a larger number of patients could really see if this therapy is as promising as we hope. The Board approved almost $8.3 million to support that work.

Seeing is believing

How promising? Well, I recently talked to Rosie Barrero, who took part in the first phase clinical trial. She told me that she was surprised how quickly she started to notice improvements in her vision:

“There’s more definition, more colors. I am seeing colors I haven’t seen in years. We have different cups in our house but I couldn’t really make out the different colors. One morning I woke up and realized ‘Oh my gosh, one of them is purple and one blue’. I was by myself, in tears, and it felt amazing, unbelievable.”

Amazing was a phrase that came up a lot yesterday when we introduced four people to our Board. Each of the four had taken part in a stem cell clinical trial that changed their lives, even saved their lives. It was a very emotional scene as they got a chance to thank the group that made those trials, those treatments possible.

We’ll have more on that in a future blog.

 

 

 

 

Translating great stem cell ideas into effective therapies

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CIRM funds research trying to solve the Alzheimer’s puzzle

In science, there are a lot of terms that could easily mystify people without a research background; “translational” is not one of them. Translational research simply means to take findings from basic research and advance them into something that is ready to be tested in people in a clinical trial.

Yesterday our Governing Board approved $15 million in funding for four projects as part of our Translational Awards program, giving them the funding and support that we hope will ultimately result in them being tested in people.

Those projects use a variety of different approaches in tackling some very different diseases. For example, researchers at the Gladstone Institutes in San Francisco received $5.9 million to develop a new way to help the more than five million Americans battling Alzheimer’s disease. They want to generate brain cells to replace those damaged by Alzheimer’s, using induced pluripotent stem cells (iPSCs) – an adult cell that has been changed or reprogrammed so that it can then be changed into virtually any other cell in the body.

CIRM’s mission is to accelerate stem cell treatments to patients with unmet medical needs and Alzheimer’s – which has no cure and no effective long-term treatments – clearly represents an unmet medical need.

Another project approved by the Board is run by a team at Children’s Hospital Oakland Research Institute (CHORI). They got almost $4.5 million for their research helping people with sickle cell anemia, an inherited blood disorder that causes intense pain, and can result in strokes and organ damage. Sickle cell affects around 100,000 people in the US, mostly African Americans.

The CHORI team wants to use a new gene-editing tool called CRISPR-Cas9 to develop a method of editing the defective gene that causes Sickle Cell, creating a healthy, sickle-free blood supply for patients.

Right now, the only effective long-term treatment for sickle cell disease is a bone marrow transplant, but that requires a patient to have a matched donor – something that is hard to find. Even with a perfect donor the procedure can be risky, carrying with it potentially life-threatening complications. Using the patient’s own blood stem cells to create a therapy would remove those complications and even make it possible to talk about curing the disease.

While damaged cartilage isn’t life-threatening it does have huge quality of life implications for millions of people. Untreated cartilage damage can, over time lead to the degeneration of the joint, arthritis and chronic pain. Researchers at the University of Southern California (USC) were awarded $2.5 million to develop an off-the-shelf stem cell product that could be used to repair the damage.

The fourth and final award ($2.09 million) went to Ankasa Regenerative Therapeutics, which hopes to create a stem cell therapy for osteonecrosis. This is a painful, progressive disease caused by insufficient blood flow to the bones. Eventually the bones start to rot and die.

As Jonathan Thomas, Chair of the CIRM Board, said in a news release, we are hoping this is just the next step for these programs on their way to helping patients:

“These Translational Awards highlight our goal of creating a pipeline of projects, moving through different stages of research with an ultimate goal of a successful treatment. We are hopeful these projects will be able to use our newly created Stem Cell Center to speed up their progress and pave the way for approval by the FDA for a clinical trial in the next few years.”

Key Steps Along the Way To Finding Treatments for HIV on World AIDS Day

Today, December 1st,  is World AIDS Day. It’s a day to acknowledge the progress that is being made in HIV prevention and treatment around the world but also to renew our commitment to a future free of HIV. This year’s theme is Leadership. Commitment. Impact.  At CIRM we are funding a number of projects focused on HIV/AIDS, so we asked Jeff Sheehy, the patient advocate for HIV/AIDS on the CIRM Board to offer his perspective on the fight against the virus.

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At CIRM we talk about and hope for cures, but our actual mission is “accelerating stem cell treatments to patients with unmet medical needs.”

For those of us in the HIV/AIDS community, we are tremendously excited about finding a cure for HIV.  We have the example of Timothy Brown, aka the “Berlin Patient”, the only person cured of HIV.

Multiple Shots on Goal

Different approaches to a cure are under investigation with multiple clinical trials.  CIRM is funding three clinical trials using cell/gene therapy in attempts to genetically modify blood forming stem cells to resist infection with HIV.  While we hope this leads to a cure, community activists have come together to urge a look at something short of a “home run.”

A subset of HIV patients go on treatment, control the virus in their blood to the point where it can’t be detected by common diagnostic tests, but never see their crucial immune fighting CD4 T cells return to normal levels after decimation by HIV.

For instance, I have been on antiretroviral therapy since 1997.  My CD4 T cells had dropped precipitously, dangerous close to the level of 200.  At that level, I would have had an AIDS diagnosis and would have been extremely vulnerable to a whole host of opportunistic infections.  Fortunately, my virus was controlled within a few weeks and within a year, my CD T cells had returned to normal levels.

For the immunological non-responders I described above, that doesn’t happen.  So while the virus is under control, their T cell counts remain low and they are very susceptible to opportunistic infections and are at much greater risk of dying.

Immunological non-responders (INRs) are usually patients who had AIDS when they were diagnosed, meaning they presented with very low CD4 T cell counts.  Many are also older.  We had hoped that with frequent testing, treatment upon diagnosis and robust healthcare systems, this population would be less of a factor.  Yet in San Francisco with its very comprehensive and sophisticated testing and treatment protocols, 16% of newly diagnosed patients in 2015 had full blown AIDS.

Until we make greater progress in testing and treating people with HIV, we can expect to see immunological non-responders who will experience sub-optimal health outcomes and who will be more difficult to treat and keep alive.

Boosting the Immune System

A major cell/gene trial for HIV targeted this population.  Their obvious unmet medical need and their greater morbidity/mortality balanced the risks of first in man gene therapy.  Sangamo, a CIRM grantee, used zinc finger nucleases to snip out a receptor, CCR5, on the surface of CD4 T cells taken from INR patients.  That receptor is a door that HIV uses to enter cells.  Some people naturally lack the receptor and usually are unable to be infected with HIV.  The Berlin Patient had his entire immune system replaced with cells from someone lacking CCR5.

Most of the patients in that first trial saw their CD4 T cells rise sharply.  The amount of HIV circulating in their gut decreased.  They experienced a high degree of modification and persistence in T stem cells, which replenish the T cell population.  And most importantly, some who regularly experienced opportunistic infections such as my friend and study participant Matt Sharp who came down with pneumonia every winter, had several healthy seasons.

Missed Opportunities

Unfortunately, the drive for a cure pushed development of the product in a different direction.  This is in large part to regulatory challenges.  A prior trial started in the late 90’s by Chiron tested a cytokine, IL 2, to see if administering it could increase T cells.  It did, but proving that these new T cells did anything was illusive and development ceased.  Another cytokine, IL 7, was moving down the development pathway when the company developing it, Cytheris, ceased business.  The pivotal trial would have required enrolling 4,000 participants, a daunting and expensive prospect.  This was due to the need to demonstrate clinical impact of the new cells in a diverse group of patients.

Given the unmet need, HIV activists have looked at the Sangamo trial, amongst others, and have initiated a dialogue with the FDA.  Activists are exploring seeking orphan drug status since the population of INRs is relatively small.

Charting a New Course

They have also discussed trial designs looking at markers of immune activity and discussed potentially identifying a segment of INRs where clinical efficacy could be shown with far, far fewer participants.

Activists are calling for companies to join them in developing products for INRs.  I’ve included the press release issued yesterday by community advocates below.

With the collaboration of the HIV activist community, this could be a unique opportunity for cell/gene companies to actually get a therapy through the FDA. On this World AIDS Day, let’s consider the value of a solid single that serves patients in need while work continues on the home run.

NEWS RELEASE: HIV Activists Seek to Accelerate Development of Immune Enhancing Therapies for Immunologic Non-Responders.

Dialogues with FDA, scientists and industry encourage consideration of orphan drug designations for therapies to help the immunologic non-responder population and exploration of novel endpoints to reduce the size of efficacy trials.

November 30, 2016 – A coalition of HIV/AIDS activists are calling for renewed attention to HIV-positive people termed immunologic non-responders (INRs), who experience sub-optimal immune system reconstitution despite years of viral load suppression by antiretroviral therapy. Studies have shown that INR patients remain at increased risk of illness and death compared to HIV-positive people who have better restoration of immune function on current drug therapies. Risk factors for becoming an INR include older age and a low CD4 count at the time of treatment initiation. To date, efforts to develop immune enhancing interventions for this population have proven challenging, despite some candidates from small companies showing signs of promise.

“We believe there is an urgent need to find ways to encourage and accelerate development of therapies to reduce the health risks faced by INR patients,” stated Nelson Vergel of the Program for Wellness Restoration (PoWeR), who initiated the activist coalition. “For example, Orphan Drug designations[i] could be granted to encourage faster-track approval of promising therapies.  These interventions may eventually help not only INRs but also people with other immune deficiency conditions”.

Along with funding, a major challenge for approval of any potential therapy is proving its efficacy. While INRs face significantly increased risk of serious morbidities and mortality compared to HIV-positive individuals with more robust immune reconstitution, demonstrating a reduction in the incidence of these outcomes would likely require expensive and lengthy clinical trials involving thousands of individuals. Activists are therefore encouraging the US Food & Drug Administration (FDA), industry and researchers to evaluate potential surrogate markers of efficacy such as relative improvements in clinical problems that may be more frequent in INR patients, such as upper respiratory infections, gastrointestinal disease, and other health issues.

“Given the risks faced by INR patients, every effort should be made to assess whether less burdensome pathways toward approval are feasible, without compromising the regulatory requirement for compelling evidence of safety and efficacy”, said Richard Jefferys of the Treatment Action Group.

The coalition is advocating that scientists, biotech and pharmaceutical companies pursue therapeutic candidates for INRs. For example, while gene and anti-inflammatory therapies for HIV are being assessed in the context of cure research, there is also evidence that they may have potential to promote immune reconstitution and reduce markers associated with risk of morbidity and mortality in INR patients. Therapeutic research should also be accompanied by robust study of the etiology and mechanisms of sub-optimal immune responses.

“While there is, appropriately, a major research focus on curing HIV, we must be alert to evidence that candidate therapies could have benefits for INR patients, and be willing to study them in this context”, argued Matt Sharp, a coalition member and INR who experienced enhanced immune reconstitution and improved health and quality of life after receiving an experimental gene therapy.

The coalition has held an initial conference call with FDA to discuss the issue. Minutes are available online.

The coalition is now aiming to convene a broader dialogue with various drug companies on the development of therapies for INR patients. Stakeholders who are interested in becoming involved are encouraged to contact coalition representatives.

[i] The Orphan Drug Act incentivizes the development of treatments for rare conditions. For more information, see:  http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/ucm2005525.htm

For more information:

Richard Jefferys

Michael Palm Basic Science, Vaccines & Cure Project Director
Treatment Action Group richard.jefferys@treatmentactiongroup.org

Nelson Vergel, Program for Wellness Restoration programforwellness@gmail.com

 

 

Failed stem cells may cause deadly lung disease

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Breathing is something we take for granted. It’s automatic. We don’t need to think about it. But for people with pulmonary fibrosis, breathing is something that is always on their minds.

Pulmonary fibrosis (PF) is a disease where the tissue in your lungs becomes thick and stiff, even scarred, making it difficult to breathe. It can be a frightening experience; and it doesn’t just affect your lungs.

Because your lungs don’t work properly they aren’t able to move as much oxygen as you need into your bloodstream, and that can have an impact on all your other organs, such as your brain and heart. There are some treatments but no cures, in large part because we didn’t know the cause of the disease. Many patients with PF live only 3-5 years after diagnosis.

Now a new CIRM-funded study from researchers at Cedars-Sinai has uncovered clues as to the cause of the disease, and that in turn could pave the way to new treatments.

The study, published in the journal Nature, found that a class of stem cells in the lung, called AEC2s, are responsible for helping repair damage caused by things such as pollution or infection. People who have PF have far fewer of these AEC2 cells, and those cells also had a much lower concentration of a chemical substance called hyaluronan, which is essential for repair damaged tissue.

They tested this theory with laboratory mice and found that by removing hyaluronan the mice developed thick scarring in their lungs.

In a news release from Cedars-Sinai Carol Liang, the study’s first author, said knowing the cause of the problem may help identify potential solutions:

“These findings are the first published evidence that idiopathic pulmonary fibrosis is primarily a disease of AEC2 stem cell failure. In further studies, we will explore how the loss of hyaluronan promotes fibrosis and how it might be restored to cell surfaces. These endeavors could lead to new therapeutic approaches.”

Knowing that a problem with AEC2 cells causes PF means the researchers can now start testing different medications to see which ones might help boost production of replacement AEC2 cells, or help protect those still functioning.

Discovering stem cells and science at Discovery Day

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The CIRM booth at Discovery Day at AT&T Park

Someone stole my thigh bone. One minute it was there. The next, gone. I have narrowed down the list of suspects to the more than 25,000 people attending Discovery Day at San Francisco’s AT&T Park.

To be honest, the bone was just a laminated image of a bone, stuck to the image of a person drawn on a white board. We were using it, along with laminated images of a brain, liver, stomach and other organs and tissues, to show that there are many different kinds of stem cells in the body, and they all have different potential uses.

The white board and its body parts were gimmicks that we used to get kids to come up to the CIRM booth and ask what we were doing. Then, as they played with the images, and tried to guess which stem cells went where, we talked to their parents about stem cell research, and CIRM and the progress being made.

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Dr. Karen Ring explaining embryonic development to kids

We also used Play Doh so that the kids could model cell division and specialization during embryonic development. But mostly it was so the kids could play with the Play Doh while we talked to their parents.

It is shameless I know but when you are competing against more than 130 other booths for people’s attention – and some of these booths had live snakes, virtual reality devices, or they just let kids throw and hit things – you have to be creative.

And creativity was certainly the key word, because Discovery Day – part of the annual week-long Bay Area Science Fair – was filled with booths from companies and academic institutions promoting every imaginable aspect of science.

So why were we there? Well, first, education has been an important part of CIRM’s mission ever since we were created. Second, we’re a state agency that gets public funding so we feel we owe it to the public to explain how their money is being used. And third, it’s just a lot of fun.

NASA was there, talking about exploring deep space. And there were booths focused on exploring the oceans, and saving them from pollution and over-fishing. You could learn about mathematics and engineering by building wacky-looking paper airplanes that flew long distances, or you could just sit in the cockpit of a fighter jet.

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And everywhere you looked were families, with kids running up to the different booths to see what was there. All they needed was a little draw to get them to stick around for a few minutes, so you could talk to them and explain to them what stem cells are and why they are so amazing. Some of the kids were fascinated and wanted to know more: some just wanted to use the Play Doh;  at least one just wanted to eat the Play Doh, but fortunately we were able to stop that happening.

It was an amazing sight to see a baseball stadium filled with tens of thousands of people, all there to learn about science. At a time when we are told that kids don’t care about science, that they don’t like math, this was the perfect response. All you had to do was look around and see that kids were fascinated by science. They were hungry to learn how pouring carbon dioxide on a candle puts out the flame. They delighted in touching an otter pelt and feeling how silky smooth it is, and then looking at the pelt under a microscope to see just how extraordinarily dense the hairs are and how that helps waterproof the otter.

And so yes, we used Play Doh and a white board person to lure the kids to us. But it worked.

There was another booth where they had a couple of the San Francisco 49er’s cheerleaders in full uniform. I don’t actually know what that had to do with teaching science but it was very popular with some of the men. Maybe next year I could try dressing up like that. It would certainly draw a crowd.


Check us out on Instagram to learn more about CIRM’s educational outreach efforts.

We had a lot of fun this weekend teaching young minds about what stem cells are and where they are located in the human body at the @bayareascience #DiscoveryDay festival. We had one activity where kids learned about embryonic stem cells and development using playdoh and another white board activity about adult stem cells. Students learned that each organ has its own set of adult stem cells that can regenerate lost or damaged cells in that specific organ. It was really fun to explain to kids and their parents why stem cells and regenerative medicine research are important. • • • #BASF2016 #stemcells #stemcellresearch #stemeducation #STEM #teaching #education #research #attpark #CIRM #development #embryonicstemcells

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