Neural stem cells show signs of treating ALS (Lou Gehrig’s disease) in mice

A consortium of researchers around the U.S. used transplanted neural stem cells (shown here) to treat a mouse model of ALS.

CIRM grantees at Sanford-Burnham were part of a consortium that found transplanted neural stem cells slows the progress of a form of Lou Gehrig’s disease (amyotrophic lateral sclerosis or ALS) in mice.

It’s still too early to celebrate – mice are quite different than humans, and treating a disease in one doesn’t necessarily translate into a therapy for the other – but it’s nice to see signs of hope for a disease that’s desperately in need of a therapy. ALS is a fatal disease in which the nerve cells that control movement die.

Sanford-Burnham described the study, which was published in Science Translational Medicine, on their blog:

In this study, researchers at multiple institutions conducted 11 independent studies to test neural stem cell transplantation in a well-established mouse model of ALS. They all found that this cell therapy reduced the symptoms and course of the ALS-like disease. They observed improved motor performance and respiratory function in treated mice. Neural stem cell transplant also slowed the disease’s progression. What’s more, 25 percent of the treated ALS mice in this study survived for one year or more—roughly three to four times longer than untreated mice.

They went on to describe how the cells helped slow the disease:

Transplanted neural stem cells helped the ALS mice, but not for the obvious reason—not because they became nerve cells, replacing those missing in the ALS spinal cord. The biggest impact actually came from a series of other beneficial neural stem cell activities. It turns out neural stem cells produce protective molecules. They also trigger host cells to produce their own protective molecules. In turn, these factors help spare host nerve cells from further destruction.

We have more information on our website about our stem cell funding for ALS.

A.A.

Most popular stem cell stories of 2012: diabetes, spinal cord injury, and what the future holds

This is the time of year when everybody is posting their year end best-of list. Not wanting to be left out, I went through to find our top blog entries of the year. What I learned is that readers are eager to know about progress toward therapies, which makes perfect sense. As an agency, we exist because voters wanted to accelerate the path to new therapies and that’s just what we’ve been trying to do.

1. Our top blog post is about a video we produced to explain an exciting project working toward a therapy for diabetes. I think this post is so popular because it not only explains the science, it includes two people who are living with diabetes explaining why it’s so important to find a cure.

2011 Annual Report: Toward a stem cell therapy for diabetes

2. In June, CIRM grantee Irv Weissman at Stanford University wrote about the barriers that stand in the way of developing new therapies. That publication includes perhaps my all time favorite line of any scientific paper: “So, whom have I failed to annoy here?” He’s outspoken, but only because he cares. Here’s an excerpt from the paper, which appeared in Cell Stem Cell:

Remember, right now our patients, friends, and families are contracting diseases that have a very short window of opportunity in which regenerative therapies can save them, and each delay removes a cohort of them from possible cures. We should not fail them.

Irv Weissman on the many barriers to stem cell therapies and why they matter

3. Next on our list of most popular blogs is one that describes a conversation I had with Katie Sharify, the fifth person to participate in Geron’s now-closed trial for spinal cord injury. In includes a link to a video of our conversation, in which she talks about how she made the decision to participate and what she hoped to get out of the trial. “I was part of something that was bigger than me, and bigger than all of you.”

Fifth Geron stem cell trial participant discusses her experience

4. Earlier this year we filmed an Ask the Expert video in which we talked to CIRM grantee Lawrence Goldstein about stem cell therapies for Alzheimer’s disease. As part of that conversation, we discussed what he saw in the future for stem cell science. In our blog entry about that video we quote Goldstein, “If the public continues to adequately fund research with stem cells we will see breakthroughs that are absolutely unexpected and that will change the way that we deliver medicine.”

Looking into the stem cell crystal ball: what’s next?

5. In September of this year, StemCells Inc reported that two patients in their clinical trial for spinal cord injury were recovering well and seemed to have gained some sensation. We weren’t funding the work at the time, though the trial is based on work by our grantees at UC Irvine. The company recently received a disease team award to further fund this trial.

CIRM grantees show preliminary signs of success in spinal cord injury trial

Our YouTube site shows a similar focus on stem cell therapies, with videos about Parkinson’s disease, Diabetes, ALS, and macular degeneration in the top five. The only top video that didn’t describe a CIRM team working toward therapies was one about a talk given by Craig Venter about the power of genomic research.

A.A.

Stem cell who’s who: 2012 Person of the Year

Earlier this year CIRM grantee and stem cell blogger Paul Knoepfler requested nominations for his stem cell person of the year competition. In a video that accompanies his request, Knoepfler says he was hoping to honor someone other than the usual stodgy scientists—people who have gone out of their way to propel the field through legislation, advocacy, or in the case of some nominees through sheer force of personality (that’s you Roman Reed).

Knoepfler recently posted the top 16 in a veritable who’s who of stem cell notables. Some are scientists, but are nominated for their extra-scientific activities fighting stem cell tourism, others are bloggers, stem cell advocates, entrepreneurs, foundation directors, and patients fighting for cures.

It should also be noted that two CIRM folks were nominated, but Knoepfler put them out of the running due to conflicts of interest – he himself has CIRM funding. Elona Baum has worked tirelessly at CIRM to bring much-needed industry involvement into the stem cell field and Patricia Olson leads our scientific activities.

It’s fun to look down Knoepfler’s list and see familiar names, many of whom I’ve worked with while trying to tell CIRM’s story. Judy Roberson, Roman Reed, Don Reed, Jeanne Loring, Katie Sharify and Keri Kimler all grace videos on our YouTube channel (the links lead to their videos), and several of those people regularly show up to our meetings and advocate to our board for research funding.

I don’t envy Knoepfler the task of picking just one person from the list. We are lucky to work in a field that includes so many dedicated people pushing for stem cell-based therapies.

A.A.

Old drug finds new life treating muscular dystrophy

Dr. Stanley Nelson

CIRM grantees at UCLA published a paper last week showing that a drug that’s currently being tested for other uses might also be effective in treating people with muscular dystrophy. The group got a $6 million Early Translational award from CIRM to turn this research into a clinical trial for the disease (here’s a description of their project).

The researchers have a great story to tell. The lead author Stanley Nelson and his wife Carrie Miceli, who also participated in the research, have a young son with muscular dystrophy. UCLA writes about the couple, using the acronym DMD for a specific type of muscular dystrophy called Duchenne muscular dystrophy:

The research by Miceli and Nelson, who are married, is driven by more than just scientific curiosity. Their youngest son, Dylan, 11, was diagnosed with DMD in 2004. While he’s still ambulatory — many DMD patients require the use of wheelchairs by about age 10 — Dylan can no longer run or climb stairs, and he can’t shoot a basketball over his head like other boys his age. Despite these challenges, Miceli said Dylan remains a happy, funny and engaged boy, full of life and passion. 

“We entered into this field because of the diagnosis of our son, but we hope our research can help many others,” she said. “There are drugs that can help manage the symptoms of the disease but nothing that changes its course dramatically. We’re trying to correct the defect that causes DMD with highly personalized genetic medicine.”

Their research was published in the journal Science Translational Medicine. Although the potential therapy involves a drug, not a stem cell, the team used patient-specific stem cells to find that drug. This type of stem cell screen is becoming an increasingly common way of finding new therapies. The group started with cells from people with Duchenne muscular dystrophy. Those cells contain the mutation that causes the muscles to waste away. They then converted those cells to embryonic-like iPS cells, which have the ability to form any cell in the body. Then, they matured those cells into muscle cells that, since they have the mutation, also show signs of the disease in a lab dish. They could then expose those cells to many thousands of different drugs, looking for ones that seem to improve the symptoms.

Over the next few years they are hoping to do longer-term studies to see if the drug combination is effective over time, and then eventually start clinical trials to see if it works in people. Right now, there is no effective treatment for this fatal disease.

A.A.

ResearchBlogging.orgKendall GC, Mokhonova EI, Moran M, Sejbuk NE, Wang DW, Silva O, Wang RT, Martinez L, Lu QL, Damoiseaux R, Spencer MJ, Nelson SF, & Miceli MC (2012). Dantrolene enhances antisense-mediated exon skipping in human and mouse models of duchenne muscular dystrophy. Science translational medicine, 4 (164) PMID: 23241744

Has that stem cell treatment been tested? Better check before paying

Image: Credit: Nissim Benvenisty, via Wikimedia Commons

We’ve written quite a bit about the dangers of stem cell tourism and about unregulated treatments in the U.S. The concern is that people are paying large amounts of money to receive injections of cells that haven’t been tested for safety.

Scientific American recently published a story that’s receiving a lot of attention in stem cell circles that makes clear why these unregulated injections are a problem. It highlights the story of a woman who had received injections in her face of stem cells taken from her own fat. She ended up with bone growing in her eyelid.

The story quotes CIRM grantee Paul Knoepfler, who is a stem cell researcher at UC Davis. He has blogged frequently about his concerns regarding stem cell clinics offering unregulated treatments. In the story he says:

“Many of us are super excited about stem cells, but at same time we have to be really careful. These aren’t your typical drugs. You can stop taking a pill and the chemicals go away. But if you get stem cells, most likely you will have some of those cells or their effects for the rest of your life. And we simply don’t know everything they are going to do.”

CIRM is working with our grantees and with the FDA to help move promising therapies through clinical trials and into doctor’s offices. That process takes time, but through those trials we get some assurance that the cells aren’t going to cause any harm. This page has more information about our initiatives to bring therapies through clinical trials to patients.

A.A.

CIRM Research in a Global Perspective

Sixteen years ago the first edition of The Global Burden of Disease was released in hard cover. I remember lugging the 1,022 page edition, complete with tables of data, around campus as a masters of public health student at UC Berkeley. Professor Kirk Smith made us use the tables to calculate how disease patterns vary around the world, and perhaps most importantly how such data can be used to guide health policy decisions.

Fast-forward to 2012, where a tool from the Institute for Health Metrics Evaluation saves the need for lugging and data entry. It also makes it much easier to see the worldwide importance of finding therapies for some of the major diseases that are a focus of CIRM research such as HIV/AIDS, cancer and diabetes, among others.

You can play with this online tool here. It incorporates yesterday’s release of the 2010 Global Burden of Disease data into a fabulous interactive visualization display.

The tool allows one to analyze disease patterns by age, region of the world and disease type and to compare the patterns to those seen in 1990. I spent last night showing my wife and son how important some of the diseases CIRM is focused on developing treatments for are. We examined diabetes, HIV/AIDS and cancer to discoverer the following:

  • North America ranks as the third highest region in the world for disability attributed to diabetes (note this figure include both Type I and II);
  • HIV/AIDS is the leading killer of 30-39 year olds globally
  • Cancer is the leading cause of death of 5-9 year old children in North America

I was pleased to see that the 2010 results were widely publicized and reporting good news on the health front. Specifically, that fewer children are dying or being disabled from preventable diseases. The Lancet reports:

Although 52·8 million deaths occurred in 2010 (in 1990, the figure was 46·5 million deaths), great progress is being made in population health. Life expectancies for men and women are increasing. A greater proportion of deaths are taking place among people older than 70 years. The burdens of HIV and malaria are falling. Far fewer children younger than 5 years are dying. Infectious diseases are increasingly being controlled. In some parts of the world, there has been substantial progress in preventing premature deaths from heart disease and cancer.

One can gain endless insights into world health and health policy decisions with this visualization tool. Best of all, no more late nights having to manually enter data from my text book.

G.L.

Guest blogger Alan Trounson — November’s stem cell research highlights

Alan Trounson, CIRM President

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

The full report this month includes a couple important advances in understanding the underlying nature of stem cells that result from reprogramming adult cells to become like embryonic stem cells, induced pluripotent stem cells (iPS). Although the science that revealed that this feat could be accomplished won the Nobel prize this year, much remains unknown about the resulting cells.

You can read that full report here, but I want to focus this blog on another paper that appeared in November, one that I frankly never expected to read. A team at Stanford placed embryonic stem cells directly into animal patients and they did not see wide spread formation of tumors. The very hallmark of pluripotent stem cells, whether embryonic or iPS cells, is that when they are transplanted directly they uniformly form a type of multi-tissue tumor called a teratoma. That is why the conventional wisdom is that pluripotent cells would always be matured at least part way to the desired final adult cell before ever being transplanted into patients.

The Stanford team only saw tumors in two out of 42 mice that received the transplants. In taking the leap to try this experiment, the researchers were building on knowledge built up in recent years about the key roll of the environment around stem cells in determining their fate; that is determining what type of adult cell they mature into. In this case they wanted the cells to become bone to replace a hole they had created in the animals’ skulls. They placed the cells on a synthetic scaffold to make the cells array as in bone and laced the scaffold with a protein known to enhance bone formation. The team attributed an additional push to form bone to signals the stem cells received from the neighboring bone at the graft site.

Two tumors out of 42 is still two too many for any regulatory approval of the process. But the team wrote that they hope to enhance the technique to yield completely tumor-free recipients. One thing they are suggesting is adding other cell types to the scaffold to act as “chaperones” for the stem cells.

My full report is available online, along with links to my reports from previous months.

A.T.

Coalition helps keep our embryonic stem cell work legal

After three days of being with a few hundred like-minded and energized folks at the World Stem Cell Summit in Florida, I was able to hop up the coast to D.C. for the annual meeting of the Coalition for the Advancement of Medicine, an event that I can usually only catch a piece of by phone. CAMR is the main organization that has fought to preserve our right to fund embryonic stem cell research and for the right of the National Institutes of Health to join us in funding that work..

The group has been instrumental in helping keep the work legal in most states. Its effort was also critical to the passage of legislation that would allow federal funding in 2005 and 2006. Unfortunately those bills were the subjects of two of President Bush’s first vetoes. But the coalition also worked to make sure Obama’s presidential order in March 2009, authorizing NIH funding for embryonic stem cell research, was one of the earliest executions of one of his campaign promises. We heard at the CAMR meeting that there are now 186 embryonic stem cell lines approved for NIH funding.

When the coalition was formed we did not expect to be spending time in litigation. (My former colleagues at Harvard helped found the group and I attended an early organizing meeting.) But when the Shelley vs. Sibelius case was filed in August 2009, we did file a brief, and have done so at each stage of this prolonged case. The CAMR board believes those briefs were influential because it was easier for us to say certain things than for the Justice Department to do so. The next key date in the case is January 4. That is the next chance for the Supreme Court to decide whether to hear it, though it may not decide then, or it could decide and not announce it at that time.

Status quo is holding on Capitol Hill. There was not any legislative activity last year and we heard today that none is expected this year unless the Supreme Court case goes the wrong way.

A member at the meeting observed, “At CAMR we always hoped we could get to the point where politics was no longer getting in the way of good science, and Sally Temple’s presentation today showed we are getting to that point. And I think CAMR has had a large role of getting us there.” (We did a short blog about that talk at the World Stem Cell Summit.)

That is at least in Washington.

Activity has moved to the states. David Chatel, of the National Multiple Sclerosis Society follows the issue at the state level for CAMR. The coalition has tracked legislation and ballot issue in 19 states in the past year. The CAMR board meets weekly to decide if action is needed at the state level. They took actions in two state sending letters to members of two legislatures: those in Virginia and Oklahoma.

CIRM is one of some 90 organizations that are members of the group ranging from major research universities to patient advocacy organizations like the Parkinson’s Action Network. I am proud to have been there at the beginning of the coalition that has certainly proven its worth over the years.

D.G.

Jonathan Thomas discussion IOM report on CIRM: "Bold social innovation"

Jonathan Thomas is chair of CIRM’s governing board, the Independent Citizens’ Oversight Committee

From the very beginning in 2004, when voters approved Proposition 71, creating the stem cell agency and providing us with the money to help fund research, CIRM has been a unique organization. No other state agency was ever created in this way. As we set out to start work we had no models to follow, we had to start from scratch. So we did. And I think we did a remarkable job. But there is always room for improvement and with that in mind in 2011 we asked the Institute of Medicine (IOM) to come in and take a look at everything we do from how we are run to how we fund research, and let us know what we are doing well and where they think we could do better.

This assessment has been underway since I became Chair of the agency’s governing board, the Independent Citizens Oversight Committee (ICOC), last year, and I’ve eagerly awaited the IOM’s report on how we’ve been doing and how we can improve.

Why the IOM? Well they are considered the gold standard for scientific policy and health care. They set up a 13-member panel led by Harold Shapiro, PhD, a former President of Princeton University, which included experts from a wide variety of scientific and governmental fields. Over an 18-month period they held three public meetings, several briefings and asked us a lot of tough questions.

The result is a detailed report that came out this week looking at every aspect of the stem cell agency’s operations and organization. It’s a comprehensive and thoughtful look at us, and a quite complimentary one too.

Among the areas the IOM singled out for praise are:

  • CIRM’s collaborations with funders in the US and around the world saying this “substantially enhanced California’s position as one of the key international hubs of activity in regenerative medicine.”
  • Science and research – “CIRM has been highly effective in building an impressive research portfolio.”
  • Global impact – “the work of CIRM-sponsored researchers continues to enrich regenerative medicine everywhere,” and that “CIRM and those it has funded have set in motion a significant scientific enterprise.”
  • Grants management – “Given the complexity of this endeavor…..the overall success of the grant management infrastructure is impressive.”
  • Industry engagement – “CIRM has created an exemplary training program and seeded a pipeline of intellectual property and translational projects that are primed for industry involvement, outside funding, and unique therapy delivery mechanisms.”

Those findings are a testament to the experience, expertise, and commitment of the staff at the stem cell agency, and of our governing board. It’s a very small organization by most standards – just over 50 employees – but our staff do an extraordinary amount of work, and high quality work at that. All that was reflected in the IOM report that called the agency “a bold social innovation.”

While it’s nice to get praise we also wanted to know where we could do better, and the report highlighted some areas and made some recommendations about where and how we might improve our performance. Those include:

  • Changes to the composition and structure of our governing board, the Independent Citizens Oversight Committee (ICOC)
  • Changes in the roles board members play in the grant application review process
  • Revisions to our Conflict of Interest policies
  • Sponsor training programs on ethical issues and stem cells
  • Establish a Scientific Advisory Board
  • Develop a sustainability platform
  • Increase industry representation on our governing board, the Independent Citizens Oversight Committee (ICOC), and other key working groups

We take the report, and all its observations, seriously and over the next few months the agency’s management team and our governing board will consider how best to respond to the report and its recommendations.

J.T.

Short takes from patient advocates at the World Stem Cell Summit #wscs12

Posts from my colleagues who were at the World Stem Cell Summit this week reminded me about the short video interviews we did last year with patient advocates. One of the best parts of this meeting is always seeing the scientists mix with the patient advocates and meet the people who really stand to benefit from their research.

We talked with several advocates in our booth about what they were getting out of the meeting. You can see all of those short interviews on our blog entry from that meeting.

One of my favorites was my talk with Keri Kimler, Vice President for Texans for Stem Cell Research, who is a tireless advocate for stem cell research and for educating people about the value of the work. She’s always bustling around that meeting, meetings scientists and other advocates and talking up Texan research. Here she is:

A.A.