iPSC banking

Meeting the scientists who are turning their daughter’s cells into a research tool – one that could change her life forever

/ Kevin McCormack / 1 Comment

There’s nothing like a face-to-face meeting to really get to know someone. And when the life of someone you love is in the hands of that person, then it’s a meeting that comes packed with emotion and importance.

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Lilly Grossman

Last week Gay and Steve Grossman got to meet the people who are working with their daughter Lilly’s stem cells. Lilly was born with a rare, debilitating condition called ADCY5-related dyskinesia. It’s an abnormal involuntary movement disorder caused by a genetic mutation that results in muscle weakness and severe pain. Because it is so rare, little research has been done on developing a deeper understanding of it, and even less on developing treatments.

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The Grossmans and Chris Waters meet the Buck team

 

That’s about to change. CIRM’s Induced Pluripotent Stem Cell  iPSC Bank – at the Buck Institute for Research on Aging – is now home to some of Lilly’s cells, and these are being turned into iPS cells for researchers to study the disease, and to hopefully develop and test new drugs or other therapies.

Gay said that meeting the people who are turning Lilly’s tissue sample into a research tool was wonderful:

“I think meeting the people who are doing the actual work at the lab is so imperative, and so important. I want them to see where their work is going and how they are not only affecting our lives and our daughter’s life but also the lives of the other kids who are affected by this rare disease and all rare diseases.”

Joining them for the trip to the Buck was Chris Waters, the driving force behind getting the Bank to accept new cell lines. Chris runs Rare Science a non-profit organization that focuses on children with rare diseases by partnering with patient family communities and foundations.

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Steve and Gay Grossman and Chris Waters

In a news release, Chris says there are currently 7,000 identified rare diseases and 50 percent of those affect children; tragically 30 percent of those children die before their 5th birthday:

“The biggest gap in drug development is that we are not addressing the specific needs of children, especially those with rare diseases.  We need to focus on kids. They are our future. If it takes 14 years and $2 billion to get FDA approval for a new drug, how is that going to address the urgent need for a solution for the millions of children across the world with a rare disease? That’s why we created Rare Science. How do we help kids right now, how do we help the families? How do we make change?”

Jonathan Thomas, the Chair of the CIRM Board, said one way to help these families and drive change is by adding samples of stem cells from rare diseases like ADCY5 to the iPSC Bank:

“Just knowing the gene that causes a particular problem is only the beginning. By having the iPSCs of individuals, we can start to investigate the diseases of these kids in the labs. Deciphering the biology of why there are similarities and dissimilarities between these children could the open the door for life changing therapies.”

When CIRM launched the iPSC Initiative – working with CDI, Coriell, the Buck Institute and researchers around California – the goal was to build the largest iPSC Bank in the world.  Adding new lines, such as the cells from people with ADCY5, means the collection will be even more diverse than originally planned.

Chris hopes this action will serve as a model for other rare diseases, creating stem cell lines from them to help close the gap between discovery research and clinical impact. And she says seeing the people who are turning her idea into reality is just amazing:

“Oh my gosh. It’s just great to be here, to see all these people who are making this happen, they’re great. And I think they benefit too, by being able to put a human face on the diseases they are working on. I think you learn so much by meeting the patients and their families because they are the ones who are living with this every day. And by understanding it through their eyes, you can improve your research exponentially. It just makes so much more sense.”

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RARE Bears for RARE Science

To help raise funds for this work Rare Science is holding a special auction, starting tomorrow, of RARE Bears. These are bears that have been hand made by, and this is a real thing, “celebrity quilters”, so you know the quality is going to be amazing. All proceeds from the auction go to help RARE Science accelerate the search for treatments for the 200 million kids around the world who are undiagnosed or who have a rare disease.

 

Making a deposit in the Bank: using stem cells from children with rare diseases to find new treatments

/ Kevin McCormack / Leave a comment

Part of The Stem Cellar series on ten years of iPS cells

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For Chris Waters, the motivation behind her move from big pharmaceutical companies and biotech to starting a non-profit organization focused on rare diseases in children is simple: “What’s most important is empowering patient families and helping them accelerate research to the clinical solutions they so urgently need for their child ,” she says.

Chris is the founder of Rare Science. Their mission statement – Accelerating Cures for RARE Kids – bears a striking resemblance to ours here at CIRM, so creating a partnership between us just seemed to make sense. At least it did to Chris. And one thing you need to know about Chris, is that when she has an idea you should just get out of the way, because she is going to make it happen.

“The biggest gap in drug development is that we are not addressing the specific needs of children, especially those with rare diseases.  We need to focus on kids. They are our future. If it takes 14 years and $2 billion to get FDA approval for a new drug, how is that going to help the 35% of the 200 million children across the world that are dying before 5 years of age because they have a rare disease? That’s why we created Rare Science. How do we help kids right now, how do we help the families? How do we make change?”

Banking on CIRM for help

One of the changes she wanted to make was to add the blood and tissue samples from one of the rare disease patient communities she works with to the CIRM Induced Pluripotent Stem Cell Bank. This program is collecting samples from up to 3,000 Californians – some of them healthy, some suffering from diseases such as autism, Alzheimer’s, heart, lung and liver disease and blindness. The samples will be turned into iPS cells – pluripotent stem cells that have the ability to be turned into any other type of cell in the body – enabling researchers to study how the diseases progress, and hopefully leading to the development of new therapies.

 

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Lilly Grossman: photo courtesy LA Times

Chris says many kids with rare diseases can struggle for years to get an accurate diagnosis and even when they do get one there is often nothing available to help them. She says one San Diego teenager, Lilly Grossman, was originally diagnosed with Cerebral Palsy and it took years to identify that the real cause of her problems was a mutation in a gene called ADCY5, leading to abnormal involuntary movement. At first Lily’s family felt they were the only ones facing this problem. They have since started a patient family organization (ADCY5.org) that supports others with this condition.

“Even though we know that the affected individuals have the gene mutation, we have no idea how the gene causes the observable traits that are widely variable across the individuals we know.  We need research tools to help us understand the biology of ADCY5 and other rare disease – it is not enough to just know the gene mutation. We always wanted to do a stem cell line that would help us get at these biological questions.”

Getting creative

But with little money to spend Chris faced what, for an ordinary person, might have been a series of daunting obstacles. She needed consent forms so that everyone donating tissue, particularly the children, knew exactly what was involved in giving samples and how those samples would be used in research.  She also needed materials to collect the samples. In addition she needed to find doctors and sites around the world where the families were located to help with the sample collection.  All of this was going to cost money, which for any non-profit is always in short supply.

So she went to work herself, creating a Research Participant’s Bill of Rights – a list of the rights that anyone taking part in medical research has. She developed forms explaining to children, teenagers and parents what happens if they give skin or blood samples as part of medical research, telling them how an individual’s personal medical health history may be used in research studies. And then she turned to medical supply companies and got them to donate the tubes and other materials that would be needed to collect and preserve the tissue and blood samples.

Even though ADCY5 is a very rare condition, Chris has collected samples from 42 individuals representing 13 different families, some affected with the condition as well as their unaffected siblings and parents. These samples come from families all around the world, from the US and Europe, to Canada and Australia.

“With CIRM we can build stem cell lines. We can lower the barrier of access for researchers who want to utilize these valuable stem cell lines that they may not have the resources to generate themselves.  The cell lines, in the hands of researchers, can potentially accelerate understanding of the biology. They can help us identify targets to focus on for therapies. They can help us screen currently approved medications or drugs, so we have something now that could help these kids now, not 14 years from now.”

The samples Chris collects will be made available to researchers not just here in the US, but around the world. Chris hopes this program will serve as a model for other rare diseases, creating stem cell lines from them to help close the gap between discovery research and clinical impact.

Rare bears for rare disease

But in everything she does, in the end it always comes down to the patient families. Chris says so many children and families battling a rare disease feel they are alone. So she created with her team, the RARE Bear program to let them know they aren’t alone, that they are part of a worldwide community of support. She says each bear is handmade by the RARE Bear Army which spans 9 countries including 45 states in the US.  Each RARE Bear is different, because “they are all one of a kind bears for one of a kind kids. And that’s why we are here, to help rare kids one bear at a time.”  The RARE Bear program, also helps with rare disease awareness, patient outreach and rare disease community building which is key for RARE Science Research Programs.

It’s working. Chris recently got this series of photos and notes from the parents of a young girl in England, after they got their bear.

“I wanted to say a huge heartfelt thank you for my daughters Rare bear. It arrived today to Essex, England & as you can see from my pictures Isabella loves her already! We have named her Faith as a reminder to never give up!”

DISCUSSing iPSC Derivation

/ cirmweb / Leave a comment

Geoff Lomax is CIRM’s Senior Officer for Medical and Ethical Standards. He has been working in the implementation of CIRM’s iPSC Banking Program.

The ability to create high-quality stem cell lines depends, in part, on the generosity of donors. For example, CIRM is sponsoring an induced pluripotent stem cell bank (iPSC bank) that will eventually contain 9,000 stem cell lines. Each of these lines will be generated from tissue donated by 3,000 people suffering from known diseases such as Alzheimer’s disease, autism, hepatitis, blindness, heart disease—and many more. You can learn more about this important initiative here.

shutterstock_182164514

In other countries there are similar initiatives like the one sponsored by CIRM.

We also believe that our donors should have accurate information about how their donated materials will be used, so CIRM has developed variety of tools designed to educate donors. For example, each donor must go through a process called “informed consent” where they are told the details of how iPSC’s are derived and preserved in a bank. We discuss this effort here. In the context of the CIRM bank, new donors are being recruited under ethically and scientifically optimal conditions—where they can be fully informed as to how their cells will be used and how their contribution will spur stem cell research.

There are, however, existing libraries of cell and tissues that have inherent scientific value. For example, they may represent a rare or “orphan” disease. Or, they may be essential for tracking the progress of a patient’s disease over time. These collections have also been developed with the consent of the donor or patient, but, at the time of collection, iPSCs may not have even existed. One question that frequently arises is: can these cells be used for iPSC derivation, research and banking? It is not an abstract concern; CIRM and others often get questions about the adequacy of donor consent for precisely this purpose.

In 2013, CIRM, the NIH and the International Stem Cell Forum (ISCF)/McGill University formed the DISCUSS Project (Deriving Induced Stem Cells Using Stored Specimens) to engage the boarder research community on this issue. Rosario Isasi, a project collaborator from ISCF/McGill University, said that her research tells us that investigators around the world are asking the same questions about use of existing cell lines. To help inform researchers, we started by publishing a report on this very subject. The report included nine points to consider when answering the question of whether existing cell libraries can be used for iPSC research.

We followed this initial effort with a series of meetings and workshops to get reactions to our proposed points to consider. The process culminated with a workshop in March where researchers from around world provided recommendations to the DISCUSS team. Sara Hull, a project collaborator from the NIH, noted that the international perspectives were key to producing a greatly improved product. A major workshop theme was the importance of having an effective management system in place, making sure that the cells are used in a way that is consistent with the donor consent. Participants described a number of specific mechanisms that should be used by the research community to ensure cells are used appropriately. Participants emphasized that having effective systems in place to manage cells and iPSC lines in accordance with donors wishes serves to build trust.

Our workshop report elaborates on specific steps researchers and stem cell banks should take to ensure cell lines are used appropriately. The report also includes a revised set of points to consider based on comments received from meetings and workshops.

The DISCUSS Team looks forward to working with the research community to develop consensus for the responsible use of donated materials in stem cell research.

Geoff Lomax

DISCUSSing iPSC Derivation

/ cirmweb / Leave a comment

Geoff Lomax is CIRM’s Senior Officer for Medical and Ethical Standards. He has been working in the implementation of CIRM’s iPSC Banking Program.

The ability to create high-quality stem cell lines depends, in part, on the generosity of donors. For example, CIRM is sponsoring an induced pluripotent stem cell bank (iPSC bank) that will eventually contain 9,000 stem cell lines. Each of these lines will be generated from tissue donated by 3,000 people suffering from known diseases such as Alzheimer’s disease, autism, hepatitis, blindness, heart disease—and many more. You can learn more about this important initiative here.

shutterstock_182164514

In other countries there are similar initiatives like the one sponsored by CIRM.

We also believe that our donors should have accurate information about how their donated materials will be used, so CIRM has developed variety of tools designed to educate donors. For example, each donor must go through a process called “informed consent” where they are told the details of how iPSC’s are derived and preserved in a bank. We discuss this effort here. In the context of the CIRM bank, new donors are being recruited under ethically and scientifically optimal conditions—where they can be fully informed as to how their cells will be used and how their contribution will spur stem cell research.

There are, however, existing libraries of cell and tissues that have inherent scientific value. For example, they may represent a rare or “orphan” disease. Or, they may be essential for tracking the progress of a patient’s disease over time. These collections have also been developed with the consent of the donor or patient, but, at the time of collection, iPSCs may not have even existed. One question that frequently arises is: can these cells be used for iPSC derivation, research and banking? It is not an abstract concern; CIRM and others often get questions about the adequacy of donor consent for precisely this purpose.

In 2013, CIRM, the NIH and the International Stem Cell Forum (ISCF)/McGill University formed the DISCUSS Project (Deriving Induced Stem Cells Using Stored Specimens) to engage the boarder research community on this issue. Rosario Isasi, a project collaborator from ISCF/McGill University, said that her research tells us that investigators around the world are asking the same questions about use of existing cell lines. To help inform researchers, we started by publishing a report on this very subject. The report included nine points to consider when answering the question of whether existing cell libraries can be used for iPSC research.

We followed this initial effort with a series of meetings and workshops to get reactions to our proposed points to consider. The process culminated with a workshop in March where researchers from around world provided recommendations to the DISCUSS team. Sara Hull, a project collaborator from the NIH, noted that the international perspectives were key to producing a greatly improved product. A major workshop theme was the importance of having an effective management system in place, making sure that the cells are used in a way that is consistent with the donor consent. Participants described a number of specific mechanisms that should be used by the research community to ensure cells are used appropriately. Participants emphasized that having effective systems in place to manage cells and iPSC lines in accordance with donors wishes serves to build trust.

Our workshop report elaborates on specific steps researchers and stem cell banks should take to ensure cell lines are used appropriately. The report also includes a revised set of points to consider based on comments received from meetings and workshops.

The DISCUSS Team looks forward to working with the research community to develop consensus for the responsible use of donated materials in stem cell research.

Geoff Lomax