President Obama proclaimed December 1 World AIDS Day, writing:
Today, we reflect on the strides we have taken toward overcoming HIV/AIDS, honor those who have made our progress possible, and keep in our thoughts all those who have known the devastating consequences of this illness.
One of those invited to the White House event was CIRM board member Jeff Sheehy, who is a long-time HIV/AIDS advocate. He was also recently named to the POZ 100 “Soldiers”. The magazine wrote of this group:
All wars—hot, cold and metaphorical—are won or lost on the front lines. The fight against HIV/AIDS is no different. Without the science—a cure, a vaccine and other biomedical prevention—the battle cannot be won. However, the science is only half the battle.
Jeff once told me that when he joined CIRM’s board eight years ago, he didn’t see a role for stem cells in an HIV/AIDS treatment. Now, CIRM has committed $40 million toward HIV/AIDS projects and two teams of researchers from City of Hope and UCLA are working toward clinical trials. Two researchers from the City of Hope-led team were also named to the POZ list, John Zaia and Paula Cannon. (We’ve written previously about success of these two teams and their approaches.)
Here’s Jeff talking about his hopes for a cure, with John Zaia of City of Hope discussing his team’s work.
Jeff is one of ten patient advocates on our board who help keep the board’s focus where it belongs – on finding therapies for incurable diseases and injuries. Clearly, we’re not alone in thinking that he’s a valuable advocate for finding a cure for all those who are living with HIV/AIDS.
One of the unique things about the stem cell agency is the strong presence of patient advocates on our governing board, the Independent Citizens Oversight Committee (ICOC). Out of 27 members on the ICOC ten are patient advocates (bios of all board members are available here). It’s designed to ensure that we never lose sight of our main goal, to help push research that will produce therapies to benefit patients.
Now, we are delighted to welcome a new patient advocate member to our board, Diane Winokur, a tireless advocate for Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig’s disease) and Mulitiple Sclerosis. Diane has been appointed by Lt. Governor Gavin Newsom who praised her, saying she “is known and respected by her colleagues for her dedication and commitment to the lives of the patients and families who suffer from neurodegenerative diseases.”
Diane’s passion and dedication to finding therapies for ALS comes from her own personal experience with the disease. She lost two sons to the non-familial form of ALS. Her youngest son, Douglas, was diagnosed with ALS in 1995 and passed away in 1997. Her oldest son, Hugh, was diagnosed with ALS in 2005 and passed away five years later.
At a governing board meeting in July of this year she joined other patients and advocates who spoke eloquently and powerfully as they urged the board to approve an $18 million dollar Disease Team research grant to a team from Cedars-Sinai Regenerative Medicine Institute. Their voices were heard. The ICOC approved the grant. You can see that video here:
Driven by her experiences she has been an active leader nationally and internationally in science and biotechnology. She served on the ALS Association’s National Board of Trustees for five years and is presently an officer on the Golden West Chapter’s Board of Directors.
In a news release welcoming her appointment, Jonathan Thomas, PhD, JD, the Chair of the ICOC said: “We are delighted and honored to have Diane join the ICOC. Her knowledge, expertise and leadership will be a tremendous addition to the ICOC and help guide us in our work.”
Diane replaces David Serrano Sewell, who is stepping down after completing his term and what Lt. Gov. Newsom called his “invaluable service.”
CIRM President Alan Trounson, PhD (well what president did you think we meant?) is in high demand as a speaker and presenter for his thoughts on regenerative medicine in general, and the work of CIRM in particular.
He recently had a cross-Atlantic email conversation with Alex Lovering, the associate editor of London-based International Innovation, a publication dedicated to disseminating the latest science, research and technological innovations on a global level. You can read the full interview here.
In the interview, Dr. Trounson said that in the past year alone there have been many exciting advances in the field of stem cell research, and he points out three in particular:
• A few groups have reported the ability to coax stem cells into forming complex, multilayer tissue; something that is key to many even simple repair scenarios
• Other researchers have made some very fundamental advances in scaling up stem cell and progenitor cell production, which is critical to commercializing most cell-based therapies, in particular, allogeneic ones [i.e. therapies using cells from a donor]
• During the past year, several teams have greatly expanded on a discovery initially made with muscle cells that you can directly reprogram one adult cell to the function of a different adult cell without first taking it back to a pluripotent state such as an iPS cell. This opens up whole new avenues to therapy that had not been expected
In the interview Dr. Trounson covers a number of topics from our international collaborations to our increasing efforts to move the most promising therapies from the lab into clinical trials in people.
In the past few years CIRM has helped fund the creation of 12 new state-of-the-art research labs (the last one opened recently, here’s a blog on that). Dr. Trounson says as he travels around California the researchers working in the facilities:
frequently pull me aside to tell me how great the facilities are for accelerating their work, in providing ready access both to specialized equipment and valuable collaborators. Furthermore, we surveyed our grantees this winter and found that they had cited our facilities to attract follow-on funding of $190 million in new grants from NIH and other non-CIRM sources. That represents more real leverage.
Dr. Trounson ends by saying he is confident that we are entering a new era of biological developments which:
will enable us to utilize stem cells for biomedicine across an extraordinary breadth of disease, injury and infection. I see major advances in personalized medicine, increased understanding of disease and infection and unparalleled opportunity to improve quality of life for many people of the world.
Move over Drs. Gurdon and Yamanaka*, there’s a new kid in town. Or at least there will be if our old friend, UC Davis stem cell research Paul Knoepfler, PhD, has anything to do with it.
Paul is not just a respected researcher and an associate professor of cell biology and human anatomy, he’s also an avid blogger and a tireless advocate for stem cell research. As part of his efforts to increase awareness and create a little more excitement about the science – and when was the last time you heard the words ‘science’ and ‘excitement’ in the same sentence – Paul has created a new award for the “Stem Cell Person of the Year.”
The goal of the award is to honor someone who has made a significant contribution to the field of stem cell science. It could be a researcher, a patient advocate, someone from the biotech industry or even a lawyer. The only criteria that matters is that their work has made a real difference in stem cell science in the last year.
Paul says there are lots of other awards out there but most of those are determined by ‘stodgy committees’ and that those nominating systems are old fashioned and usually quite predictable. He says we shouldn’t limit awards to those who wear a lab coat.
“The stem cell field is really transcending the lab,” he says, “and it’s going to clinics and patients and doctors and even into the courts – there’s legal cases – so it’s really a very diverse universe for the stem cell field and I think this award will kind of reflect that diversity.”
Paul, who has a great sense of humor, is not joking about this either. He’s putting up $1,000 of his own money as part of the prize. “It’s kind of fun,” he says, “and it’s something that I’m hoping I can do every year. It would also be a reward for risk taking, creativity, and be breaking with tradition and be something new in that regard.”
Anyone is eligible for the award – except people who work with him in his lab. If you want to find out how to nominate someone all the details are available on the Knoepfler Lab Stem Cell Blog. Paul plans to pick five finalists and interview each of them by phone/Skype. There is also an online component where members of the public can vote for their favorite. The winner will be announced in early January.
* Dr. John Gurdon and Dr. Shinya Yamanaka were awarded the 2012 Nobel Prize for Physiology or Medicine for their pioneering work in stem cell research. But you knew that, right? If not, see our previous blog posts here, here, and here.
heart muscle cells matured from embryonic stem cells, courtesy of Sanford-Burnham Medical Research Institute
Here’s the dilemma a group of CIRM grantees near San Diego, CA set out to resolve: hearts contain stem cells, but those cells don’t always repair damage to the heart after a heart attack.
“They need to be stimulated,” John Cashman told the San Diego Union Tribune. “They need to have a good reason to turn into heart cells.” Cashman, from the Human BioMolecular Institute, is one of the authors of a new study published in the Journal of Medicinal Chemistry which identifies a chemical that might just provide that stimulation.
Sanford-Burnham’s Mark Mercola, who worked with Cashman, added: “Regeneration is thought to be an adaptive response to injury, but it just doesn’t work all that well. The problem is that it needs to be goosed up.” The group is working with the company ChemRegen to develop their chemical into a possible therapy.
The group found a chemical called IDT-1 that turns mouse and human embryonic stem cells in to heart cells in a lab dish. The idea is that this chemical might encourage stem cells in the heart to turn into heart muscle cells and repair damage that occurs after a heart attack. Basically, IDT-1 might goose those inactivated stem cells in the heart.
Writing for the Union Tribune, Bradley Fikes explains why getting from this promising chemical to human trials takes time. Mostly, it has to do with whether the drug is going to be safe. Sure, it prods stem cells to turn into heart cells, but what good is that if it also damages the liver, or causes other harm?
But before ChemRegen can start clinical trials on a drug based on IDT-1, it must be tested for toxicity and taken through animal studies to see if it provides therapeutic benefit,” Cashman said. All told, that may cost about $3 million to $4 million, with $1 million going for toxicology studies and the rest for animal studies. ChemRegen plans to seek partnerships with drug companies or other investors to fund that work.
Then, even if the drug is safe and effective in animal studies, there’s still the concern that older adults, who are most likely to have heart attacks, might not have sufficient numbers of heart stem cells to repair the damage, even if they are properly stimulated. Mercola called that the million dollar question.
Schade D, Lanier M, Willems E, Okolotowicz K, Bushway P, Wahlquist C, Gilley C, Mercola M, & Cashman JR (2012). Synthesis and SAR of b-Annulated 1,4-Dihydropyridines Define Cardiomyogenic Compounds as Novel Inhibitors of TGFβ Signaling. Journal of medicinal chemistry PMID: 23130626
Katie Sharify talks about participating in Geron’s spinal cord injury trial
This week I was lucky enough to interview Katie Sharify in front of a group of scientists who were meeting to discuss the best ways of advancing stem cell clinical trials. Katie was the fifth and final patient to participate in Geron’s CIRM-supported clinical trial for spinal cord injury.
Katie had a great story to tell about what it’s like to be a patient in a stem cell clinical trial. She had very little understanding of the science before her injury and had very little time to get as informed as possible before making a decision about whether or not to participate. She needed to get herself educated in just six days and she needed to educate her parents (who speak little English) while also adapting to life in a wheelchair.
The trial Katie was considering was in phase I, which means that the scientists were primarily testing whether the cells were going to be safe. This is always the first phase of testing any new drug or therapy, before testing higher doses in more people in a phase II trial.
Katie told me that it would be impossible not to hope that a trial would help her, but that by the time she made the decision to participate she knew she was doing it to further science, not necessarily to further her own recovery. She told the audience, “I was part of something that was bigger than me, and bigger than all of you.”
Geron’s was the first clinical trial to test a therapy based on embryonic stem cells. Soon after Katie enrolled in the trial, Geron stopped the trial for business reasons though the company remained committed to following the five patients who had already participated for the full 15 years. We wrote a Q&A about that decision here. Geron returned CIRM’s loan that supported the trial with interest.
Ever since Geron’s decision to terminate the trial there has been speculation about other companies buying those embryonic stem cell programs and picking up the trial where it left off, and about CIRM’s role in a continued trial. Recently, Geron entered into a nonbinding agreement to transfer their embryonic stem cell programs to BioTime, Inc. (here is the Geron press release). There are still a lot of unknowns in that agreement, but if it goes through it could mean that more people with recent spinal cord injuries have a chance to make a decision like Katie’s.
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.
Although this months full report showcases a couple interesting papers refining our understanding of stem cells in the brain, I want to focus this blog on something even more essential for life—eggs.
Two leading journals, Science and Nature, both published major papers in October on eggs. The article in Science detailed the work of a Japanese team that created viable mouse eggs by reprograming adult stem cells. This was an incredibly difficult feat. Eggs need to possess all the starting materials to begin to create an embryo, but they can only have one set of chromosomes including an X chromosome, unlike the two sets that would be in the initial embryo or stem cell, just like every other tissue in our bodies, except sperm of course that have a single set with either an X or Y chromosome. Eggs also need a special environment to nurture them to mature and be ready for fertilization. The stem cells this team used not only resulted in viable mouse pups, the cells also became grandparents, suggesting the offspring were pretty close to, if not completely normal.
The Nature paper describes a procedure that could allow mothers to avoid passing down certain genetic diseases to their children. About one in 5.000 people is born with a genetic disease not caused by errors in their chromosomes in their cells’ nucleus, but rather errors in the genes carried in structures within the cells called mitochrondria that generate energy for the rest of the cell. Gene variants in these mini-organelles and errors in their DNA have been linked to many rare diseases. But we only have one copy of each of these genes, because we only inherit the ones that were in the mitochondria of our mother’s eggs.
The research team from Oregon worked with human eggs and was able to produce genetically normal stem cell lines from eggs carrying mitochondrial mutations. They accomplished this feat by transferring the chromosomes from the nucleus of the original egg into donor eggs that had normal mitochondria.
The Oregon team predicted that the first human birth from using this procedure could come within three years. However, the Japanese team said that moving their work from the mouse model to human could take many years. Nonetheless, both projects have given us valuable new insight into an aspect of human development this is still shrouded in mystery, how normal eggs mature and begin to develop into an embryo.
Embryonic stem cells matured into choroid plexus epithelial cells
We and others often write that embryonic stem cells can form all the cell types of the body. Well, what we really mean is that they can form the three basic cell layers, and that those layers generate all the cell types of the body. Scientists haven’t actually turned embryonic stem cells into each of the hundreds of cell types that make up our bodies.
Now researchers at University of California, Irvine have ticked one more cell type off the list of those that had not yet been generated. These cells could play an important role in treating neurodegenerative diseases such as Alzheimer’s disease.
The cells go by the full name of choroid plexus epithelial cells, or CPECs. They are cells of the brain that are responsible for making the fluid that cushions the brain and spinal column. They cells also filter waste or other foreign matter from that fluid. These cells don’t function properly in people with Alzheimer’s disease, leading some scientists to guess that transplanted healthy cells might help treat the disease. The problem in testing that idea has been the lack of human CPECs to transplant.
That absence led UCI’s Edwin Monuki and graduate student Momoko Watanabe to mature embryonic stem cells to form CPECs, starting with both mouse and human stem cells. They published their discovery in the Journal of Neuroscience.
Now that they’ve figured out how to generate these cells, a lot of work lies ahead. They hope to find out if the cells can be transplanted to help generate more fluid to bath the brain and spinal column, and if that function helps treat symptoms of Alzheimer’s. They also think the cells could be engineered to produce drugs that could be pumped into the brain along with that fluid to treat diseases of the brain.
Finally, the team hopes the cells in a lab dish could be used to screen for drugs that might be used to improve the function of those cells in a person’s brain.
“Our method is promising, because for the first time we can use stem cells to create large amounts of these epithelial cells, which could be utilized in different ways to treat neurodegenerative diseases.”
All of these approaches hold promise, but will require some long hours in the lab before we know if they work.
In the movie ‘Field of Dreams’ the lead character, played by Kevin Costner, is told to turn his cornfield into a baseball field in the belief that “if you build it, he will come.”
Well, under a similar if less mystical guidance we helped the University of California Santa Barbara turn 10,000 square feet of antiquated lab space into a brand new, state-of-the-art stem cell research facility. And having built it he did come, the ‘he’ in question being one of the top stem cell researchers in the UK, Pete Coffey. (Here’s more about Coffey and others who were lured to the state.)
When the UC Santa Barbara Center for Stem Cell Biology and Engineering opened up it was the 12th and final research lab that CIRM helped fund around the state. Those facilities stretch from UC Davis in Sacramento in the north, to UC San Diego in the south. To do that we put in $271 million dollars, which the institutions used to leverage an additional almost $900 million in institutional funds and philanthropic contributions to complete the facilities. We have a list of all those facilities and the amount of money they raised on our website.
As former State Senator Art Torres, JD, Vice Chair of our Governing Board says in our press release, “Those buildings not only created world class research facilities, they also provided thousands of new construction jobs at a time of record unemployment in that industry, and they generated new tax dollars for the state.” An estimated $100 million in taxes to be precise.
We helped support the building of new labs for a number of reasons. One, having the best facilities can help attract the best scientists to work there. And secondly, at the time we decided to make these awards under our Major Facilities Grant Program there were strict rules on embryonic stem cell research that meant researchers could only use NIH funding to work on a small number of pre-existing embryonic stem cell lines. This effectively prevented them from working on new cell lines, severely limiting their ability to advance the science.
CIRM decided to help the leading research institutions around California create new, ‘specialized’, research facilities where they could use CIRM or outside funding to work with new embryonic stem cell lines – or any other kind of stem cell. Obviously the political scene has changed since then but the need for state-of-the-art facilities hasn’t. That’s why these 12 new specialized research labs are still so important; they can attract top scientists from around the US and indeed the world, to California.
That’s what has happened at a number of the new labs around the state, including UCSB, which used the promise of a new lab and a CIRM new Leadership Award to recruit Pete Coffey, PhD, from the University College of London in the UK, where he was considered a rising star in the stem cell research field. He’s part of a team with researchers at the University of Southern California who are working on a stem cell therapy for macular degeneration.
“To be part of UC Santa Barbara at this time is extremely exciting. Today we’re actually opening the center for stem cell biology and engineering, bringing two components together which are not available anywhere else in the world, engineering and stem cell biology together, to transform and actually speed what is very dear to my heart, which is the translation of science to it’s clinical use.”
Having the best facilities and researchers is still no guarantee of success. But it certainly increases the odds. As Damon Runyon once said: “It may be that the race is not always to the swift, nor the battle to the strong – but that’s the way to bet.”
We’re betting they do great things at UCSB and at the 11 other new research facilities we helped build.
This video talks about the 12 facilities and the jobs and tax revenues they created:
Several conflicting stories have been circulating this week regarding the use of stem cells to treat heart damage after a heart attack. They all came out of the American Heart Association meeting that’s taking place this week in Los Angeles.
One study found that stem cells taken from a heart attack patient’s own bone marrow did help the hearts beat more effectively. Another study found the opposite. Those who got stem cells were no better off than people who didn’t.
A final study found that stem cells taken from either a patient’s own bone marrow or from the bone marrow of a donor could lead to improvements. These patients could walk farther and the scars on their hearts were smaller, but the hearts weren’t actually pumping more blood.
So, what to believe? Do stem cells heal broken hearts?
The answer for now is maybe, to some extent. That’s why scientists carry out clinical trials before giving supposed therapies broadly to people who might not benefit. With each of these trials we have more information about exactly which types of stem cells are effective, when they should be given, how they need to be given and the type of damage each cell type can treat.
There are many more clinical trials currently underway, testing different types of stem cells in different configurations to see if they help heal heart tissue. One of those came out of a CIRM disease team, and recently received more money from CIRM to start the clinical trial. We don’t know if the trial will succeed, but whatever happens those scientists will add another piece to the puzzle of how best to repair heart damage with stem cells.
The Stem Cellar 