What’s the big idea? Or in this case, what’s the 19 big ideas?

supermarket magazineHave you ever stood in line in a supermarket checkout line and browsed through the magazines stacked conveniently at eye level? (of course you have, we all have). They are always filled with attention-grabbing headlines like “5 Ways to a Slimmer You by Christmas” or “Ten Tips for Rock Hard Abs” (that one doesn’t work by the way).

So with those headlines in mind I was tempted to headline our latest Board meeting as: “19 Big Stem Cell Ideas That Could Change Your Life!”. And in truth, some of them might.

The Board voted to invest more than $4 million in funding for 19 big ideas as part of CIRM’s Discovery Inception program. The goal of Inception is to provide seed funding for great, early-stage ideas that may impact the field of human stem cell research but need a little support to test if they work. If they do work out, the money will also enable the researchers to gather the data they’ll need to apply for larger funding opportunities, from CIRM and other institutions, in the future

The applicants were told they didn’t have to have any data to support their belief that the idea would work, but they did have to have a strong scientific rational for why it might

As our President and CEO Randy Mills said in a news release, this is a program that encourages innovative ideas.

Randy Mills, Stem Cell Agency President & CEO

Randy Mills, CIRM President & CEO

“This is a program supporting early stage ideas that have the potential to be ground breaking. We asked scientists to pitch us their best new ideas, things they want to test but that are hard to get funding for. We know not all of these will pan out, but those that do succeed have the potential to advance our understanding of stem cells and hopefully lead to treatments in the future.”

So what are some of these “big” ideas? (Here’s where you can find the full list of those approved for funding and descriptions of what they involve). But here are some highlights.

Alysson Muotri at UC San Diego has identified some anti-retroviral drugs – already approved by the Food and Drug Administration (FDA) – that could help stop inflammation in the brain. This kind of inflammation is an important component in several diseases such as Alzheimer’s, autism, Parkinson’s, Lupus and Multiple Sclerosis. Alysson wants to find out why and how these drugs helps reduce inflammation and how it works. If he is successful it is possible that patients suffering from brain inflammation could immediately benefit from some already available anti-retroviral drugs.

Stanley Carmichael at UC Los Angeles wants to use induced pluripotent stem (iPS) cells – these are adult cells that have been genetically re-programmed so they are capable of becoming any cell in the body – to see if they can help repair the damage caused by a stroke. With stroke the leading cause of adult disability in the US, there is clearly a big need for this kind of big idea.

Holger Willenbring at UC San Francisco wants to use stem cells to create a kind of mini liver, one that can help patients whose own liver is being destroyed by disease. The mini livers could, theoretically, help stabilize a person’s own liver function until a transplant donor becomes available or even help them avoid the need for liver transplantation in the first place. Considering that every year, one in five patients on the US transplant waiting list will die or become too sick for transplantation, this kind of research could have enormous life-saving implications.

We know not all of these ideas will work out. But all of them will help deepen our understanding of how stem cells work and what they can, and can’t, do. Even the best ideas start out small. Our funding gives them a chance to become something truly big.


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CRISPR cluster: How the media spotlight is focusing on gene editing tool

Illustration by Ashley Mackenzie: from New York Times Sunday Magazine

Illustration by Ashley Mackenzie: from New York Times Sunday Magazine

Getting in-depth stories about science in general, and regenerative medicine in particular, into the mainstream media is becoming increasingly hard these days. So when you get one major media outlet doing a really long, thoughtful piece about a potential game-changing gene-editing technology it’s good news. But when you get three major media outlets, all reporting on the same technology, all in the space of less than one week, and all devoting lots of words to the pieces, then it’s really a cause for celebration.

That’s what happened in the last few days with features on the gene editing technology CRISPR in the New York Times Sunday Magazine,  the New Yorker Magazine,  and STAT, a new online health and life-sciences publication produced by the Boston Globe.

Making the story personal

Feng Zhang: photo courtesy of the Broad Institute

Feng Zhang: photo courtesy of the Broad Institute

Each takes a similar approach, focusing on the individuals behind the new approach – Feng Zhang at Harvard/MIT and Jennifer Doudna at the University of California, Berkeley. The fact that the two are involved in a fight over patent rights for the process adds an extra element of friction to a story that already has more than its share of drama.

In the New Yorker, Michael Specter neatly summarizes why so many people are excited about this technology:

“With CRISPR, scientists can change, delete, and replace genes in any animal, including us. Working mostly with mice, researchers have already deployed the tool to correct the genetic errors responsible for sickle-cell anemia, muscular dystrophy, and the fundamental defect associated with cystic fibrosis. One group has replaced a mutation that causes cataracts; another has destroyed receptors that H.I.V. uses to infiltrate our immune system.”

Jennifer Doudna: Photo courtesy of iPSCell.com

Jennifer Doudna: Photo courtesy of iPSCell.com

Sharon Begley in STAT, writes that this discovery could bring cures to some of the deadliest health problems we face, from cancer to Alzheimer’s, but that it also comes with big ethical questions hanging over it:

“He (Zhang) has touched off a global furor over the possibility that a genetics tool he developed could usher in a dystopian age of designer babies.”

Jennifer Kahn in the New York Times Sunday Magazine follows up on that thought, writing about Doudna:

“But she also notes that the prospect of editing embryos so that they don’t carry disease-causing genes goes to the heart of CRISPR’s potential. She has received email from young women with the BRCA breast-cancer mutation, asking whether CRISPR could keep them from passing that mutation on to their children — not by selecting embryos in vitro, but by removing the mutation from the child’s genetic code altogether. ‘‘So at some point, you have to ask: What if we could rid a person’s germ line, and all their future generations, of that risk?’’ Doudna observed. ‘‘When does one risk outweigh another?’’

Each article makes for fascinating reading. Collectively they highlight why CRISPR is such a hot topic, on so many different levels, in science right now.

The topic is going to be the focus of a conference, featuring scientists from the US, Europe and China, being held at the National Academy of Sciences in Washington DC the first week of December.

CIRM is also getting involved in the debate and is holding a science-policy workshop on February 4th, 2016 in Los Angeles to consider the future use of genome editing technologies in studies sponsored by CIRM.

Could We Reverse Alzheimer’s Disease with Stem Cells?

What if you could give people whose memories have been stolen the ability to remember again? I’m talking about curing a population of more than 5 million Americans living with Alzheimer’s disease (AD) – not a small task. Unfortunately, this number is predicted to more than triple by 2050, and with it so will healthcare costs and other burdens to society. The situation is dire enough that president Barack Obama signed a law last year that increased the amount of money to fund AD research, education, outreach, and caregiver support.

This weekend, a story was picked up in the news that brings hope for AD research. South China Morning Post covered a scientific study that claims it can reverse memory loss in mice with Alzheimer’s using a cell-based therapy. The study was published in Stem Cell Reports in mid October by a group of Chinese scientists.

Although the study is still in its early stages and the results are preliminary, what I like about it is its simplicity and logic. The authors decided to generate a type of nerve cell that is typically lost (or dysfunctional) in the brains of AD patients and some mouse models of AD. It’s called a basal forebrain cholinergic neuron, and it lives in an area near the bottom of our brains that’s responsible for processing certain functions such as learning and attention. The scientists proposed that they would replace these lost nerve cells in AD mice with healthy nerve cells derived from stem cells in hopes of restoring memory function.

How they did it

The authors first devised methods to make these specific nerve cells from both mouse and human embryonic stem cells in a dish. They were successful in making nerve cells that expressed the correct markers for cholinergic neurons and functioned properly, meaning they could send the correct electrical signals to other nerve cells.

The next step was to test the functionality of the nerve cells in mouse models of AD. Instead of transplanting adult nerve cells into the brain (which don’t survive very well), the authors transplanted progenitor cells, which developmentally, are more specialized than stem cells and eventually become adult nerve cells.

Untitled

Brain section from an Alzheimer’s mouse that received a transplant of progenitor cells (green) into the basal forebrain. (Yue et al., 2015)

When the mouse progenitor cells were transplanted into the basal forebrain of AD mice, most of them survived and matured into adult cholinergic nerve cells that were able to function in tandem with the original mouse nerve cells. When they transplanted human progenitor cells into the same area, a majority of the transplanted human cells did not survive (likely due to the mouse immune system rejecting them), however, the ones that did were able to turn into functioning cholinergic neurons.

Then came the final question, could the mouse and human progenitors improve the memory of these forgetful mice? The scientists compared the memories of AD mice that had received mouse or human cholinergic progenitor cells to AD mice that received no treatment and to healthy normal mice. The groups were put through a memory test where they were trained to find a hidden platform in a circular pool of water. Untreated AD mice had trouble finding the platform and couldn’t remember where it was in subsequent trials. However, the AD mice that received either mouse or human progenitor cell transplants six to eight weeks before were able to find the platform more quickly and remember where it was in multiple trials. This suggested that the transplanted nerve cells improved their ability to learn tasks and recall memories.

The water maze tests a mouse's ability to learn and recall where the hidden platform is. (Image adapted from Credit2M BioTech)

The water maze tests a mouse’s ability to learn and recall where the hidden platform is. (Image adapted from Credit2M BioTech)

Hold on: Primates before humans

So it seems from this study that replacing cholinergic nerve cells in the basal forebrain area of the brain is a potential approach to reversing memory loss in Alzheimer’s disease. However, the study’s senior author, Naihe Jing, cautioned everyone to not get ahead of themselves.

Dr. Naihe Jing, Shanghai Institutes of Biological Science

Dr. Naihe Jing

Mice are still very different from humans, so the results on mice do not guarantee the same success on human patients. Our next step is to test the method on primates. It will probably be a long time before clinical trials can be carried out on human volunteers.

 

But he also explained that his group is thoroughly testing the safety of their embryonic stem cell based therapy.

We used human embryonic stem cells because this method will eventually be used on humans. If the human neurons can get a footing and grow in the brain of a mouse, the chance is high the effect will be even better on a human host. The biggest concern of this development is safety. We were afraid that the transplanted cells would mutate to other types of neurons or even cause brain tumours. We have been improving the technology and making close observation of the mice for more than seven years. So far no mutation or cancerous development has been detected.

So while we might not have a cell therapy to treat Alzheimer’s in the near future, we can be comforted by the fact that groups like this one are taking all the precautions to develop safe and effective treatments.


Related Links:

CIRM Scholar Helen Fong on Stem Cells and Brain Disease

Helen Fong, CIRM Scholar and Research Scientist at the Gladstone Institutes

Helen Fong, CIRM Scholar and Research Scientist at the Gladstone Institutes

Meet another one of our talented CIRM Scholars, Helen Fong. She is currently a Research Scientist at the Gladstone Institutes and did her graduate work at the University of California, Irvine. Her passions include stem cells, disease modeling, and playing with differentiation protocols – the processes that tell stem cells to mature into specific tissues. As a CIRM Scholar, part of our educational training programs, Helen published four articles where she was listed as the first author. Her most recent one was a stellar study published in Stem Cell Reports using induced pluripotent stem cells (iPSCs) to model and understand a nerve cell-destroying brain disease called frontotemporal dementia.

We interviewed Helen to learn more about her work in stem cell research.


Q: What was your graduate school research on?

HF: I did my graduate work in the lab of Dr. Peter Donovan, who is a prominent germ cell and stem cell scientist, and was newly recruited to UCI when I began my studies. I was his first graduate student from UCI. Dr. Donovan’s research was focused on understanding the regulation of early human development using embryonic stem cells (ESCs) and how to improve human pluripotent stem cell culture. He was also interested in understanding the biological mechanisms that keep stem cells pluripotent (the ability to become all the other cell types in the body) and the genetic factors that are important for maintaining pluripotency. My graduate research was on understanding the basic biology of human ESCs. Specifically, I studied the role of the gene Sox2 in maintaining stem cell pluripotency and self renewal in human ESCs.

Q: What about your postdoctoral research?

HF: After my PhD, I decided to continue to work with stem cells because I knew that the field would continue to grow. There was still so much to be learned about these unique cells. I also genuinely enjoyed working with stem cells and couldn’t imagine not seeing them every day. I realized that I had a solid understanding of the basic biology of ESCs, but I wanted to use stem cells to study human disease. This ability is one of the huge selling points of working with human induced pluripotent stem cells (iPSCs) [which are created by reprogramming adult cells back to a pluripotent state]. The Gladstone Institutes was an excellent place to continue my training and to begin using iPSCs to understand neurological disease. I joined Dr. Yadong Huang’s lab in 2011 and am currently using human iPSCs to study brain degenerative diseases including frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD).

My recent publication in Stem Cell Reports used human iPSCs from a patient with FTD as a model to understand the mechanisms behind this condition. This patient carried a rare genetic mutation in the MAPT gene called TAU-A152T. Several studies have reported a number of patients with this specific mutation that could put them at risk for developing FTD, PSP, and AD. However, it wasn’t clear what this mutation was doing to cause these disorders.

One of the ways you can study neurodegenerative diseases is using stem cells derived from patients harboring the disease causing mutations. We obtained human iPSCs made from the skin cells of a patient with FTD and this TAU mutation. I then used zinc finger nuclease (ZFN) genome editing technology to genetically correct the mutation back to the wild type (normal) sequence to see if removing this mutation in the patient iPSCs would generate healthier neurons (nerve cells) that don’t have symptoms of FTD. I was able to study the disease-causing effects of the TAU mutation by comparing healthy neurons I made from the corrected (normal) iPSC line to diseased neurons made from the TAU mutant iPSC line.

Neurons generated from FTD patient iPSCs. (Image courtesy of Helen Fong)

Neurons generated from FTD patient iPSCs. (Image courtesy of Helen Fong)

The neurons that I differentiated from the iPSCs carrying the TAU mutation showed an increase in TAU protein fragmentation [meaning the protein gets degraded and isn’t present in its normal form], an abnormal characteristic that can be associated with FTD and AD. We didn’t see this phenomenon in the neurons from the corrected (normal) human iPSCs, indicating that removal of this TAU mutation could improve the symptoms of these diseases. These results were exciting because we now had a culprit for what could be causing disease in these patients with this mutation. There is still much to be learned about the mechanisms of this mutation and the iPSCs have been an invaluable resource.

Q: What was your experience like as a CIRM scholar?

HF: CIRM has funded me for almost all of my stem cell training and research. I got my first CIRM training grant as a graduate student at UCI in 2006 and was funded for three years as a postdoc at the Gladstone. So I have CIRM to thank for all of my training.

When I first started out as a CIRM scholar, I believe I was part of one of their earlier pre-doctoral training grant programs. As the program expanded, I got to meet many of the other trainees at CIRM research conferences and interact with prominent stem cell scientists in the area. This was an incredible experience because I was exposed to stem cell research outside of my own institute, and I was able to meet all the big players in the field!

CIRM has also been very generous and provided me a travel allowance to attend any scientific conference of my choice. Over the years, I’ve gone to a lot of conferences nationally and internationally including ISSCR (International Society for Stem Cell Research), Keystone symposia, and the Society for Neuroscience (SfN). I have given scientific talks both at Keystone and SfN, and they proved to be excellent exposure for my work as well as a good place to get feedback. Another one of my favorite perks was the ability to purchase reagents for my own work at my own discretion, which gave me some freedom in dictating which direction I wanted my project to go. If I wanted to study a particular protein and needed a specific antibody to do that, I was able to get it with my CIRM funding.

Q: What’s next for your career?

HF: Currently, I am hoping to wrap up the project I am working on in the lab right now and generate a publication. I plan to continue to work on stem cells in the next step of my career and to work on challenging and cutting-edge projects. I feel fortunate for all the training and resources that I’ve received that got me to where I am today, and I hope to pass on many of my skills and knowledge to budding, young scientists.

Q: What is your favorite thing about being a scientist?

HF: I really enjoy the fact that I have so much control over the fate of my stem cells. They have the ability to turn into almost any cell type, and we’ve developed so many protocols to guide them into the exact cell type we want. They don’t always behave, but I think figuring out the personality of each and every cell line is part of the fun.


Related Links:

Keeping elderly cells old to understand the aging process

Aging is a key risk factor for many diseases, particularly disorders of the brain like Alzheimer’s or Parkinson’s, which primarily occur in the elderly. So a better understanding of the aging process should provide a better understanding of these neurodegenerative diseases.

The induced pluripotent stem cell (iPSC) technique makes it possible to grow human brain cells, or neurons, in the lab from elderly patient skin samples. Unfortunately, this method has a major pitfall when it comes to aging research: reprogramming skin cells back into the embryonic stem cell-like state of iPSCs strips away many of their old age-related characteristics.

Based on data published last week in Cell Stem Cell, Salk Institute researchers used a different technique called direct reprogramming as a means to keep old cells old. This alternative method sidesteps the need to make iPSCs (which brings cells all the way back to the pluripotent state) and instead converts a skin cell directly into the desired cell type.

First author Jerome Mertens and senior author Rusty Gage (Courtesy of the Salk Institute for Biological Studies).

First author Jerome Mertens and senior author Rusty Gage (Courtesy of the Salk Institute for Biological Studies).

iPSC and direct reprogramming go head-to-head

The study, funded in part by CIRM, relied on skin samples from people ranging in age from newly born to 89 years. The team generated iPSC and iPSC-derived neurons from these samples. They also made so-called induced neurons (iNs) from the skin cells using the direct reprogramming method. Other CIRM grantees have pioneered direct reprogramming of skin into nerve cells (see link below).

Skin cell samples from elderly human donors are directly converted into induced neurons (iNs), shown. (image: Courtesy of the Salk Institute for Biological Studies)

Skin cells from elderly human donors are directly converted into induced neurons (iNs), shown. (Image courtesy of the Salk Institute for Biological Studies).

When comparing skin cells from donors younger than 40 years old versus cells from the over 40 group, the team found several genes had age-dependent activity patterns. Those differences virtually disappeared in the iPSCs and iPSC-derived neurons from the same individuals. However, unlike iPSCs, direct reprogramming of the skin cells to neurons (iNs) hung on to age-dependent differences in gene activity.

Loss of RanBP17 protein a fountain of youth in reverse

A deeper analysis identified one gene called RanBP17 whose activity levels declined with increased age of the donor in both the original skin cells and those directly converted into iNs. But when those same donor skin cells were turned into iPSCs or even iPSC-derived neurons, RanBP17 levels in the older cells were no longer reduced and were on par with RanBP17 levels in the younger cells. In follow up experiments, a reduction in RanBP17 protein led to glitches in the transport of proteins into the cell’s nucleus, which other studies have linked to neurodegenerative diseases as well as the aging process.

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Gene expression patterns of age-related factors like RanBP17 are maintained in induced neurons but not iPSCs. (Mertens et al., 2015)

Altogether, these results encourage researchers to select iNs over iPSC-derived neurons when it comes to faithfully representing the aging process of brain cells. Based on a Salk Institute press release, you can tell that professor Martin Hezter, a contributing author, is excited about future studies with iNs:

By using this powerful approach, we can begin to answer many questions about the physiology and molecular machinery of human nerve cells–not just around healthy aging but pathological aging as well.

 


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The Stem Cell Bank is open for business

Creating a stem cell bank

Creating a stem cell bank

When you go to a bank and withdraw money you know that the notes you get are all going to look the same and do the same job, namely allow you to buy things. But when you get stem cells for research that’s not necessarily the case. Stem cells bought from different laboratories don’t always look exactly the same or perform the same in research studies.

That’s why CIRM has teamed up with the Coriell Institute and Cellular Dynamics International (CDI) to open what will be the world’s largest publically available stem cell bank. It officially opened today. In September the Bank will have 300 cell lines available for purchase but plans to increase that to 750 by February 2016.

300 lines but no waiting

Now, even if you are not in the market for stem cells this bank could have a big impact on your life because it creates an invaluable resource for researchers looking into the causes of, and potential therapies for, 11 different diseases including autism, epilepsy and other childhood neurological disorders, blinding eye diseases, heart, lung and liver diseases, and Alzheimer’s disease.

The goal of the Bank – which is located at the Buck Institute for Research on Aging in Novato, California – is to collect blood or tissue samples from up to 3,000 volunteer donors. Some of those donors have particular disorders – such as Alzheimer’s – and some are healthy. Those samples will then be turned into high quality iPSCs or induced pluripotent stem cells.

Now, iPSC lines are particularly useful for research because they can be turned into any type of cell in the body such as a brain cell or liver cell. And, because the cells are genetically identical to the people who donated the samples scientists can use the cells to determine how, for example, a brain cell from someone with autism differs from a normal brain cell. That can enable them to study how diseases develop and progress, and also to test new drugs or treatments against defects observed in those cells to see which, if any, might offer some benefits.

Power of iPSCs

In a news release Kaz Hirao, Chairman and CEO of CDI, says these could be game changers:

“iPSCs are proving to be powerful tools for disease modeling, drug discovery and the development of cell therapies, capturing human disease and individual genetic variability in ways that are not possible with other cellular models.”

Equally important is that researchers in different parts of the world will be able to compare their findings because they are using the same cell lines. Right now many researchers use cell lines from different sources so even though they are theoretically the same type of tissue, in practice they often produce very different results.

Improving consistency

CIRM Board Chair, Jonathan Thomas, said he hopes the Bank will lead to greater consistency in results.

“We believe the Bank will be an extraordinarily important resource in helping advance the use of stem cell tools for the study of diseases and finding new ways to treat them. While many stem cell efforts in the past have provided badly needed new tools for studying rare genetic diseases, this Bank represents both rare and common diseases that afflict many Californians. Stem cell technology offers a critical new approach toward developing new treatments and cures for those diseases as well.”

Most banks are focused on enriching your monetary account. This bank hopes to enrich people’s lives, by providing the research tools needed to unlock the secrets of different diseases, and pave the way for new treatments.

For more information on how to buy a cell line go to http://catalog.coriell.org/CIRM or email CIRM@Coriell.org

Alzheimer’s Nightmare Spurs Comedy Fundraiser to Help Caregivers – New Video

You could have heard a pin drop in the auditorium. The audience of young stem cell researchers was gripped by every word of Lauren Miller’s heartbreaking story about the impact that Alzheimer’s disease has had on her family. Only a child when her grandfather was diagnosed with and later died of Alzheimer’s, she mistook his symptoms, like repeating stories over and over, as his way of making her laugh.

Lauren was fifteen and much more aware of the brutality of the disease when her grandmother, the vibrant family matriarch, was diagnosed with Alzheimer’s and soon, ”stopped talking, stopped walking and eventually curled up in a ball and stayed that way for the last, many months of her life.”

Miller, a screenwriter and film actress, is the Alzheimer’s patient advocate member of CIRM’s Board. Last month, she was the opening speaker at the 2015 CIRM Bridges Trainee Meeting, a two-day event which showcases the work of undergraduate and Master’s level students who, through the support of the Bridges program, conducted stem cell research at world class research institutes in California. This video recording of Lauren’s talk is a great watch but keep a hanky near by:

Her presentation clearly resonated with the students, likely because their internships were mostly centered around the laboratory bench, and Lauren’s story provided a personal, first-hand account of a disease that could one day be treated by stem cell-based therapies. Also, Lauren was just about their age when, sadly, she first realized that her mom was showing the signs of early onset Alzheimer’s. Her memory of this moment is crushing:

“I first noticed it the weekend of my college graduation. She told me the same stories a few times and deep down inside I was devastated. I said nothing to anyone. Maybe if I pretended it didn’t happen, it wouldn’t be real. Maybe it was a one-time thing and it would just go away. Of course, it didn’t go away.”

Out of this darkness, Lauren has become a source of unwavering support for other families and caregivers who are beaten down by this disease on a daily basis. She and her husband Seth Rogen founded Hilarity for Charity which she says aims, “to raise awareness about Alzheimer’s among young adults and to support those who are going through it.” In only three and a half years, Hilarity for Charity has raised almost $3 million. Recently they launched a partnership with Home Instead Senior Care and in the past six months have funded 8000 hours of free at home care to give Alzheimer’s caregivers a much needed break. For me, one of the most poignant sections of Lauren’s talk is when she read a note from one of the recipients of these grants:

“The words, ‘thank you’, just don’t seem to be enough to express my heartfelt appreciation. I’ve barely been out of Sue’s sight since 2006 and our world has shrunk to the size of her bedroom and bath with conversations from babbling to hysteria. Please accept my total gratitude for this chance to join humanity again.”

At CIRM, our Board has awarded close to $55 million to stem cell related Alzheimer’s research. These cutting edge research projects aim to gain a better understanding of the disease and to progress stem cell-based treatments into clinical trials. Here’s hoping for an accelerated cure for Alzheimer’s to end the suffering of both patients and caregivers.


Related Links:

Stories of Hope: Lauren Miller
Stories of Hope: Dick Mora
CIRM Alzheimer’s Disease Program Fact Sheet
Video: Alzheimer’s Stem Cell Research: Ask the Expert – Larry Goldstein, UCSD
Video: Neural Stem Cells Reverse Alzheimer’s-Like Symptoms

2015 Golden Globes shines light on Alzheimer’s and ALS with acting awards

In between the one-liners, surprise presenters and bottomless champagne, something remarkable happened at last night’s 72nd Golden Globe Awards.

26 awards were given last night to the best in film and television. But two in particular were especially meaningful.

Julianne Moore plays a professor grappling with Alzheimer's in Still Alice [Credit: Sony Pictures Classics]

Julianne Moore plays a professor grappling with Alzheimer’s in Still Alice [Credit: Sony Pictures Classics]

I am referring, of course, to Julianne Moore and Eddie Redmayne, who each took home awards in the lead acting categories for their portrayals of two individuals suffering from neurodegenerative diseases. Their wins not only solidified them as front-runners for the Academy Awards ceremony next month, but also gave millions of viewers a deeply intimate look at two unforgiving illnesses.

Eddie Redmayne as Stephen Hawking in The Theory of Everything [Credit: Focus Features]

Eddie Redmayne as Stephen Hawking in The Theory of Everything [Credit: Focus Features]

Renowned actress Julianne Moore was the first of the two to receive her award, winning for her role as Alice Howland, a Columbia linguistics professor diagnosed with Early-Onset Alzheimer’s disease, in the film Still Alice.

And later in the program the Globes honored Eddie Redmayne for his brilliant portrayal of Professor Stephen Hawking—a long-time sufferer of the motor neuron disease ALS—in the biopic The Theory of Everything.

These two films were particularly poignant for those in the Alzheimer’s and ALS communities—as they reveal in stark, sometimes disturbing detail, how these diseases wreak havoc on the brain and nervous system. In preparation for their roles, each spent several months speaking with patients and clinicians who see and live with the diseases every day.

For example, Moore spoke with women who—like her character Alice—were living with Early-Onset Alzheimer’s, giving her first-hand knowledge of not only how the disease affects them, but also how their families are affected.

Meanwhile, Redmayne spent significant time with Hawking himself, learning about his unique experience as a long-time ALS patient. In interviews Redmayne has said that Hawking was often present during filming. The time the two individuals spent with each other clearly paid off, and had a remarkable impact on the actor.

“It is a great privilege for me to be in this room,” Redmayne said during his Golden Globe acceptance speech. “Getting to spend time with Stephen Hawking … was one of the great, great honors of my life.”

The fact that the two lead acting awards put spotlight on these diseases was not lost on the patient advocacy communities. For example, Maria Shriver tweeted shortly after the awards ceremony:

Shriver Tweet

Shriver’s statement underscores the stark reality of awareness, or lack thereof, for neurodegenerative diseases. Here at CIRM, we are laser focused on supporting ground-breaking work in regenerative medicine that can slow, halt or even reverse these conditions. We are hopeful that these two actors’ stellar performances can help put a human face on conditions that are all too-often reduced to numbers.

This hope has thus far translated to these films’ audiences. For example, said one review of Still Alice from the New York Post:

Still Alice … presents a disease that can devastate any family, anywhere, with unsparing truth and great compassion.”

Read more about how regenerative medicine can change the face of Alzheimer’s and ALS on our Stories of Hope.

The sparrow’s dying song: a possible path toward natural, stem cell-based repair of human brain diseases

Songbird research? How the heck could studying tweeting birds lead to advancements in human health?

At a first glance, biological research in other organisms like bacteria, yeast, flies, mice and birds can seem frivolous and a waste of taxpayer money. Yet it’s astonishing how we humans share very similar if not identical functions at a cellular level with our fellow creatures on Earth. So unraveling underlying biological processes in less complex animals is essential to better understanding human biology and to finding possible paths for treating human disease.

Gambel's White-crown sparrow: could its song unlock methods for repairing the brain? (photo courtesy Lip Kee, wikimedia commons)

Gambel’s White-crown sparrow: could its song unlock methods for repairing the brain? (photo courtesy Lip Kee, wikimedia commons)

Case in point: research published in the Journal of Neuroscience last week suggests that studying brain stem cells in song birds could one day lead to methods for naturally repairing neurodegenerative disorders such as Alzheimer’s disease in humans.

The University of Washington team behind the report studies the seasonal song behavior of Gambel’s white-crown sparrows. During the spring breeding season, the population of cells in the sparrow’s brain that are responsible for singing double in number. This cell growth helps the bird to be at its peak singing performance for attracting mates and staking its territory. As breeding season recedes, these brain cells die away naturally and the sparrow’s song, no longer needed, deteriorates. When the next spring arrives the brain cells will grow again.

Audio tracing's of the sparrow's song show its degradation after breeding season each year. (T. Larson/Univ. of Washington)

Audio tracings of the sparrow’s song show its degradation after breeding season each year. (image: T. Larson/Univ. of Washington)

The team’s fascinating discovery is that the dying brain cells themselves appear to provide a signal that tells brain stem cells to multiply for the next breeding season. The scientific term for the cell die-off is called programmed cell death, or apoptosis (pronounced A-POP-TOE-SIS). There are chemicals available to block apoptosis signals. And when the research team administered these anti-apoptosis chemicals at the end of the breeding season, there was a significant reduction in newly dividing brain stem cells. This result shows that new brain stem cell growth depends on the death of brain cells associated with song.

The next step in the project is to identify the signal from the dying cells that stimulates new brain stem cell growth. Once identified, that signal could be harnessed to naturally stimulate new brain stem growth to help repair the loss of brain cells seen in aging, Parkinson’s or Alzheimer’s disease.

As he mentions in a university news story, Dr. Eliot Brenowitz, the senior author of the report, is optimistic about their prospects:

“There’s no reason to think what goes on in a bird brain doesn’t also go on in mammal brains, in human brains. As far as we know, the molecules are the same, the pathways are the same, the hormones are the same. That’s the ultimate purpose of all this, to identify these molecular mechanisms that will be of use in repairing human brains.”

To learn about CIRM-funded projects related to neurodegenerative disorders, visit our Alzheimer’s and Parkinson’s online fact sheets.

Stories of Hope: Alzheimer’s Disease

This week on The Stem Cellar we feature some of our most inspiring patients and patient advocates as they share, in their own words, their Stories of Hope.

Adele Miller knew what came next. She had lived it twice already: her father’s unraveling, due to Alzheimer’s disease, and, a few years later, her mother’s journey through the same erasure of mind and memory. So when doctors told her, at age 55, that she, too, had the disease, she remembered her parents’ difficult last years.

Lauren Miller has seen first hand how Alzheimer's can erase a lifetime's worth of memories.

Lauren Miller has seen first hand how Alzheimer’s can erase a lifetime’s worth of memories.

‘Tell no one,’ she told her family. Keep it secret.

“She was ashamed,” her daughter, actress and writer Lauren Miller, recalls. “She was so embarrassed because there’s such a stigma.” And she worried about her family. How would they handle all this? “I asked her once if she was scared,” Lauren says. “She said she wasn’t afraid for herself. But she was afraid for me, and my dad, and my brother. She knew what she’d gone through with her parents.”

Alzheimer’s disease has been a constant in the actress’s family. Perhaps that made her more attuned to the subtle changes that can herald the onset of the disease. At Lauren’s college graduation, she saw the first clues that something was amiss with her mother. She was repeating herself. Not just, “Oh, have I told you this before?” This was different. A few years later, as she and her mother prepared for a party, Lauren was stunned by the changes in her mother’s behavior. Her mother’s memory no longer seemed to function. She kept forgetting that the taco salad was vegetarian. She kept asking over and over where to throw the garbage. Lauren knew that’s not like her mother, a teacher for 35 years. So she sat down with her brother Dan and their dad. It was time to do something for Mom.

“It’s not that my dad wasn’t noticing things. But I don’t think he wanted to admit there was a problem. And he was simply too close to it,” Lauren says.

It took less than five years for Alzheimer’s disease to rob Adele Miller of nearly everything. Before she turned 60, she couldn’t write. She couldn’t speak. She didn’t even recognize her family.

The loss, the sadness, and the anger that Alzheimer’s families feel is compounded by a sense of utter helplessness against a disease that yields to no drug. But Lauren decided she would not be helpless, and in 2011, she and her husband, actor Seth Rogen, launched Hilarity for Charity, which aims to raise Alzheimer’s awareness in young people while also raising funds for the Alzheimer’s Association. This year Hilarity for Charity sponsored its first college fundraisers. It also hosts support groups for under-40 caregivers.

“Seth has the ability to reach an audience that may not know much about Alzheimer’s. His fans are 16 year old boys who aren’t generally the target for Alzheimer’s awareness,” Lauren said. “But he was able to strike a cord with a lot of these young people. We get emails from people who are 16. ‘Thank you for doing this. I felt alone. Now there’s a voice.’ This is considered an old person’s disease, but it’s really not. It affects everyone.”

In December 2013, Lauren, co-writer, producer and star of For a Good Time, Call, joined the CIRM governing Board, the Independent Citizens Oversight Committee, as a patient advocate for Alzheimer’s disease.

“Alzheimer’s research is woefully underfunded by the government, so it’s important to have bold, innovative approaches like CIRM’s to take research to the next level,” Lauren said. “Stem cell research is at the cusp of something life changing. To me, it’s one of the things closest to making a step toward treatment. I jumped at the opportunity to be part of it.”

For information about CIRM-funded Alzheimer’s disease research, visit our Alzheimer’s Fact Sheet. You can read more about Lauren’s Story of Hope on our website.