Jonathan Thomas is Chair of the CIRM governing board
Yesterday our governing board met for the first time since Geron announced the decision to terminate their stem cell research program. I wanted to take that opportunity to address the board and let them know my strong commitment to CIRM’s stem cell research program.
When Geron made their announcement our immediate concern was for the patients and their families who were disappointed at the termination of a trial that was a source of such hope for the future. Geron has been a true leader in the field and a source of inspiration for patients and their families. They broke new ground, becoming the first to start a Food and Drug Administration-reviewed trial based on human embryonic stem cells. Their efforts laid the groundwork for the two additional trials now underway for forms of blindness and for those trials that are close to submitting applications to the FDA.
However, Geron is a business. The company decided that their cancer therapies were farther along than the stem cell trial and when they held the stem cell program against the prism of economic reality they made a business decision to end the trial. The company is now looking for a partner to carry the research forward.
There are those who have extrapolated Geron’s business decision to question stem cell science. I say to those people: If you were to query the many researchers worldwide and companies involved in developing products you would hear unwavering enthusiasm for pursuing stem cell technology.
I was just at the excellent Stem Cells on the Mesa meeting in La Jolla where I heard from those researchers and investors. We spent the first day hearing about the incredible scientific advances taking place in the stem cell field. The next day we attended a business and investor partnering forum (sponsored in part by CIRM) where the same message of enthusiasm for stem cell science echoed just as strongly.
CIRM’s award to Geron was just one of the 44 projects in 26 disease areas that are in various stages of working toward clinical trials. (I blogged about those projects recently.) We remain optimistic about those research programs and are totally committed to the projects we have funded to-date and to the research we will fund in the future.
J.T.
Friday, December 9, 2011
Thursday, December 8, 2011
Stem cell discovery could help people regain smell
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| Elongated green cells are sensory neurons – which sense smells and relay that information to the brain – that originated from olfactory stem cells in the nose. Cells labeled in red are immature cells in the process of differentiating into neurons and other mature cell types. (Photomicrograph by Russell Fletcher, UC Berkeley) |
A press release by Robert Sanders at the UC Berkeley quotes lead researcher John Ngai talking about the loss of smell in old age:
“Anosmia ‑ the absence of smell ‑ is a vastly underappreciated public health problem in our aging population. Many people lose the will to eat, which can lead to malnutrition, because the ability to taste depends on our sense of smell, which often declines with age.”
“One reason may be that as a person ages, the olfactory stem cells age and are less able to replace mature cells, or maybe they are just depleted,” he said. “So, if we had a way to promote active stem cell self-renewal, we might be better able to replace these lost cells and maintain sensory function.”
“One reason may be that as a person ages, the olfactory stem cells age and are less able to replace mature cells, or maybe they are just depleted,” he said. “So, if we had a way to promote active stem cell self-renewal, we might be better able to replace these lost cells and maintain sensory function.”
The release goes on to quote Gary K. Beauchamp, director of the Monell Chemical Senses Center in Philadelphia, who was not a member of the research team. He noted that the olfactory system stands out for its ability to regenerate following injury or certain diseases.
“This new paper … presents an elegant analysis of some of the underlying genetic mechanisms regulating this regeneration,” Beauchamp said. “It also provides important insights that should eventually allow clinicians to enhance regeneration, induce it in cases where, for currently unknown reasons, olfactory loss appears permanent, or even prevent functional loss as a person ages.”
The group found a gene that seemed to be involved regulating nasal stem cells. They created mice that lacked that gene and found that the mice had more than the usual number of odor-sensing cells. Sanders goes on to write about how regulating this gene -- called p63 -- could help people regain a sense of smell:
A drug that regulates p63, or modulates one of the genes that p63, in turn, regulates, might be able to boost the number of nasal stem cells as well as the number that mature into smell neurons.
Any real world result of this work would be many years off -- the path from a mouse lacking a gene to a drug that's available to humans is a long and arduous one.
Neuron, December 8, 2011
CIRM Funding: Russell B. Fletcher, Melanie Prasol (T1-00007)
A.A.
Tuesday, December 6, 2011
Mess with the body's clock, mess with stem cells
The Canadian Stem Cell Network posted an interesting item on their blog today about the relationship between stem cells and our sleep/wake cycle (also called the circadian rhythm).
David Kent, a postdoctoral researcher at the University of Cambridge, writes about the work, which was published online in Nature November 9:
A.A.
David Kent, a postdoctoral researcher at the University of Cambridge, writes about the work, which was published online in Nature November 9:
The group of Salvador Aznar Benitah in Barcelona recently published research which links skin stem cell turnover and heterogeneity to the body’s internal clock. Their work has inspired many new studies that aim to understand the impacts of circadian rhythm on other stem cell systems.The group found that when they disrupt genes that control the sleep wake cycle, they also disrupted the balance of stem cells in a dormant versus dividing state in the mouse hair follicles. The blog goes on:
This disturbance in rhythm led to premature aging as well as an increased incidence of tumours, suggesting that we might better understand how cancers grow and progress by understanding the natural cycles our bodies go through.In the Nature paper, the authors write:
Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.Translated, what the researchers are saying is that the body's daily rhythms helps control the behavior of stem cells, at least the ones in the hair follicles. Mess with the body's clock and you mess with the ability of those stem cells to carry out their normal functions, including regulating aging and tumors.
A.A.
Monday, December 5, 2011
Clocks & stem cells: Time and tinkering to develop the best embryonic stem cells
Geoff Lomax is CIRM's Senior Officer to the Standards Working Group
The history of technology tells us that the first strategy is rarely the one that sticks. One of my favorite examples involves the English clock maker John Harris, whose many iterations of marine chronometers revolutionized sea travel. (His story is recounted in Dava Sobel’s excellent book Longitude: The True Story of a Lone Genius Who Solved the Greatest Scientific Problem of His Time.) My English grandfather also worked on clocks and marine guidance systems so I have a soft spot for the guild.
In 1730, Harris sought to produce a clock, called the H1, which could maintain accurate time on a lengthy, rough sea voyage with widely varying conditions of temperature, pressure and humidity – a great challenge in his day. This initial prototype performed well but there was a desire for a more rugged and compact design. After several iterations and another 23 years, he produced the H4, which kept time within 39 seconds during a trans Atlantic sea trial. A subsequent design, H5, was accurate within one-third of a second – revolutionary for its time.
Fast forward to 2011, in the world of human embryonic stem cell research, the cell line H9 has been revolutionary for its time – used in thousand of published studies. In a recent article, Rohun Patel and I illustrate how it is also the most widely utilized human embryonic stem cell (hESC) line by CIRM researchers. However, we also found that CIRM grantees were carrying out research with 137 other lines including 17 that had been recently derived with CIRM funding.
A recent study in Human Molecular Genetics authored by Amander Clark at University of California, Los Angeles suggests the newly derived CIRM lines may have several improvements over the earlier models. The study compared the X chromosomes of older lines, including H9, to recently derived lines. The UCLA team found that the X chromosomes in the newer lines were more active than those in the older lines, which tended to have more of the X chromosome shut down. Furthermore, the way in which those older lines shut down portions of the X chromosome deviated from how cells normally de-activate portions of the X chromosome – called “X inactivation”. In a press release from UCLA Clark said:
Human Molecular Genetics, November 30, 2011
CIRM Funding: Amander Clark (RL1-00636-1)
G.L.
The history of technology tells us that the first strategy is rarely the one that sticks. One of my favorite examples involves the English clock maker John Harris, whose many iterations of marine chronometers revolutionized sea travel. (His story is recounted in Dava Sobel’s excellent book Longitude: The True Story of a Lone Genius Who Solved the Greatest Scientific Problem of His Time.) My English grandfather also worked on clocks and marine guidance systems so I have a soft spot for the guild.
In 1730, Harris sought to produce a clock, called the H1, which could maintain accurate time on a lengthy, rough sea voyage with widely varying conditions of temperature, pressure and humidity – a great challenge in his day. This initial prototype performed well but there was a desire for a more rugged and compact design. After several iterations and another 23 years, he produced the H4, which kept time within 39 seconds during a trans Atlantic sea trial. A subsequent design, H5, was accurate within one-third of a second – revolutionary for its time.
Fast forward to 2011, in the world of human embryonic stem cell research, the cell line H9 has been revolutionary for its time – used in thousand of published studies. In a recent article, Rohun Patel and I illustrate how it is also the most widely utilized human embryonic stem cell (hESC) line by CIRM researchers. However, we also found that CIRM grantees were carrying out research with 137 other lines including 17 that had been recently derived with CIRM funding.
A recent study in Human Molecular Genetics authored by Amander Clark at University of California, Los Angeles suggests the newly derived CIRM lines may have several improvements over the earlier models. The study compared the X chromosomes of older lines, including H9, to recently derived lines. The UCLA team found that the X chromosomes in the newer lines were more active than those in the older lines, which tended to have more of the X chromosome shut down. Furthermore, the way in which those older lines shut down portions of the X chromosome deviated from how cells normally de-activate portions of the X chromosome – called “X inactivation”. In a press release from UCLA Clark said:
“The classic signature is gone, so something else is regulating X chromosome inactivation in the established cell lines,” Clark said. “It will be important not only to find out what that is, but also to discover what else is changing in the nucleus that we cannot see.”Clark’s paper shows that in stem cell research—as in other areas of innovation—it takes time and tinkering to develop the best model. The ability of CIRM-funded researchers to develop and then investigate 17 new human embryonic stem cell lines and access hundreds of others would not be possible under federal guidelines alone. Federal agencies like the NIH can’t fund research to create new stem cell lines. Clark’s paper shows the clear need for these efforts to continue under CIRM and other agencies that fund cell line derivation. In the press release she said:
“Our data highlights the importance of maintaining hESC derivation efforts. Gold standard hESC lines should be the benchmark for human pluripotent stem cell research.”Unlike Harris, stem cell researchers don’t have 23 years to tinker with their design. Patients need therapies soon, and therapy development will be bolstered by having optimal tools available to all researchers. Clark’s work shows the value to patients in those 17 lines derived by CIRM grantees, and by all those other new lines that have been and will continue to be created through sources other than federal funding.
Human Molecular Genetics, November 30, 2011
CIRM Funding: Amander Clark (RL1-00636-1)
G.L.
Friday, December 2, 2011
Guest blogger Alan Trounson — November’s stem cell research highlights
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.
This month’s literature produced a number of studies that can be glibly summarized as: Hey they work; they really work. The publications show we are starting to get a real handle on how to get stem cells to integrate and function like the desired tissue, and even to form complex structures.
The same Japanese team that was able to create a complex optic cup in a dish earlier this year, now reports that they have used embryonic stem cells to create a pituitary gland. That gland secretes the appropriate hormones and is able to correct hormone deficiency when transplanted into a mouse that lacks the pituitary gland, making the formerly lethargic animals active again.
Two teams turned embryonic stem cells into neurons that were able to integrate into the brain and show evidence that they function like the specific type of neuron that each team sought. A New York team produced dopamine-producing neurons that were able to correct some movement disorders in Parkinson’s disease models in mice, rats, and monkeys. (We blogged about that work here.) Meanwhile a Wisconsin team chose to mature the stem cells into neurons designed for memory, those in the hippocampus, and showed that they were able to integrate and fire neural signals like neighboring cells.
A Carolina team used a type of stem cell found in bone marrow and fat, mesenchymal cells, taken from the father of sheep with hemophilia, and correct the hemophilia in their sons. They did it by harvesting the stem cells and then genetically altering them so they produced Factor VIII, the blood-clotting factor that hemophiliacs don’t produce. When given to the sons, their bleeds stopped including the bleeds into their joints that had made them limp badly. The animals were able to walk normally again after the injections.
I start this month’s report with a pair of papers that seem to sort out some of the conflicting data that has been reported on stem cells for heart repair. One showed that stem cells from the bone marrow given in a couple of weeks after injury do not do improve heart function. Another showed that a different cell type—cardiac stem cells harvested from the patient’s heart—given even months after evidence of heart failure, were able to improve heart function, and in some patients for at least a year. (We blogged about that work here.) This is a critical area to gain some clarity in what cells to use and when; the burden of heart failure is a huge drain on our nation and the world.
My full report of this month’s highlights is here. I hope you will find it interesting.
A.T.
This month’s literature produced a number of studies that can be glibly summarized as: Hey they work; they really work. The publications show we are starting to get a real handle on how to get stem cells to integrate and function like the desired tissue, and even to form complex structures.
The same Japanese team that was able to create a complex optic cup in a dish earlier this year, now reports that they have used embryonic stem cells to create a pituitary gland. That gland secretes the appropriate hormones and is able to correct hormone deficiency when transplanted into a mouse that lacks the pituitary gland, making the formerly lethargic animals active again.
Two teams turned embryonic stem cells into neurons that were able to integrate into the brain and show evidence that they function like the specific type of neuron that each team sought. A New York team produced dopamine-producing neurons that were able to correct some movement disorders in Parkinson’s disease models in mice, rats, and monkeys. (We blogged about that work here.) Meanwhile a Wisconsin team chose to mature the stem cells into neurons designed for memory, those in the hippocampus, and showed that they were able to integrate and fire neural signals like neighboring cells.
A Carolina team used a type of stem cell found in bone marrow and fat, mesenchymal cells, taken from the father of sheep with hemophilia, and correct the hemophilia in their sons. They did it by harvesting the stem cells and then genetically altering them so they produced Factor VIII, the blood-clotting factor that hemophiliacs don’t produce. When given to the sons, their bleeds stopped including the bleeds into their joints that had made them limp badly. The animals were able to walk normally again after the injections.
I start this month’s report with a pair of papers that seem to sort out some of the conflicting data that has been reported on stem cells for heart repair. One showed that stem cells from the bone marrow given in a couple of weeks after injury do not do improve heart function. Another showed that a different cell type—cardiac stem cells harvested from the patient’s heart—given even months after evidence of heart failure, were able to improve heart function, and in some patients for at least a year. (We blogged about that work here.) This is a critical area to gain some clarity in what cells to use and when; the burden of heart failure is a huge drain on our nation and the world.
My full report of this month’s highlights is here. I hope you will find it interesting.
A.T.
Thursday, December 1, 2011
World AIDS Day 2011 -- Buzz about a Cure for HIV, CIRM Leading
Jeff Sheehy is director for communications at the AIDS Research Institute at UCSF, and a member of the CIRM governing board.
Two articles in major newspapers—the New York Times and London's Financial Times—are highlighting the growing movement advocating for research towards a cure for HIV in the lead up to World AIDS Day on December 1.
Advocacy for a cure has been sparked in recent years by the experience of Timothy Ray Brown, the first patient cured of HIV. It has been five years since his dangerous and high-risk procedure that also cured his leukemia and his virus remains undetectable. More recently, a patient who had some of his disease fighting T-cells re-engineered with a HIV-resistant gene is showing preliminary signs of having virus suppression without antiretroviral medications for a significant period of time. (We blogged about that work here.)
Despite these successes let's be clear, a cure is still many years off and will require the active participation of patients motivated by altruism—as my friend Nelson Vergel has noted, heroes for the cure are needed. As Vegel writes, “No one really knows the degree of altruism in the community and their willingness to accept risks for the good of all.”
But recent data from UNAIDS shows us that those heroes for the cure and the cures themselves are desperately needed. While the number of new HIV infections has stabilized and the number of deaths due to AIDS is decreasing, we are seeing two new infections for every one person we manage to get into treatment globally. We are still losing ground against the epidemic.
And in the U.S., the federal Centers for Disease Control announced this week that only about a quarter of the 1.1 million people in the U.S. living with HIV have been successfully treated with antiretrovirals to a point to where they have suppressed the virus in their bodies to very low levels.
A cure is the best way to permanently change these statistics.
The California Institute for Regenerative Medicine, of which I am a board member representing HIV/AIDS, has provided historic leadership in funding future cures. The first applications were accepted for blood and immune system stem cell (hematopoietic stem cells) gene therapy projects to permanently re-engineer a person's immune system to resist HIV almost 4 years ago. Two awards were approved two years ago (one to City of Hope and one to UCLA) and should be in clinical trials within another 2-3 years. The challenge of replicating Timothy's daring proof of concept experiment in a much safer and much more scalable manner was taken up by CIRM while the head of NIH's HIV/AIDS programs was pooh-poohing the approach as ''not practicable." He has now embraced the call for a cure and it has become one of his top research priorities.
When California voters approved Proposition 71 seven years ago, none of us knew where the science might lead. And one cannot promise a specific cure for HIV or any other disease. However, I know that the existence of CIRM has greatly helped to change the research agenda for HIV globally and I suspect this is true for many other diseases and conditions.
CIRM, the California stem cell institute, does not propose temporary or episodic relief from disease, pain and suffering. We are committed to finding cures and we are working towards them relentlessly in partnership with patients, researchers and industry across California. This year on World AIDS Day, 30 long years into the HIV/AIDS epidemic, CIRM is a beacon of hope.
This video features Jeff Sheehy and CIRM disease team leader talking about a CIRM-funded project for HIV/AIDS:
J.S.
Two articles in major newspapers—the New York Times and London's Financial Times—are highlighting the growing movement advocating for research towards a cure for HIV in the lead up to World AIDS Day on December 1.
Advocacy for a cure has been sparked in recent years by the experience of Timothy Ray Brown, the first patient cured of HIV. It has been five years since his dangerous and high-risk procedure that also cured his leukemia and his virus remains undetectable. More recently, a patient who had some of his disease fighting T-cells re-engineered with a HIV-resistant gene is showing preliminary signs of having virus suppression without antiretroviral medications for a significant period of time. (We blogged about that work here.)
Despite these successes let's be clear, a cure is still many years off and will require the active participation of patients motivated by altruism—as my friend Nelson Vergel has noted, heroes for the cure are needed. As Vegel writes, “No one really knows the degree of altruism in the community and their willingness to accept risks for the good of all.”
But recent data from UNAIDS shows us that those heroes for the cure and the cures themselves are desperately needed. While the number of new HIV infections has stabilized and the number of deaths due to AIDS is decreasing, we are seeing two new infections for every one person we manage to get into treatment globally. We are still losing ground against the epidemic.
And in the U.S., the federal Centers for Disease Control announced this week that only about a quarter of the 1.1 million people in the U.S. living with HIV have been successfully treated with antiretrovirals to a point to where they have suppressed the virus in their bodies to very low levels.
A cure is the best way to permanently change these statistics.
The California Institute for Regenerative Medicine, of which I am a board member representing HIV/AIDS, has provided historic leadership in funding future cures. The first applications were accepted for blood and immune system stem cell (hematopoietic stem cells) gene therapy projects to permanently re-engineer a person's immune system to resist HIV almost 4 years ago. Two awards were approved two years ago (one to City of Hope and one to UCLA) and should be in clinical trials within another 2-3 years. The challenge of replicating Timothy's daring proof of concept experiment in a much safer and much more scalable manner was taken up by CIRM while the head of NIH's HIV/AIDS programs was pooh-poohing the approach as ''not practicable." He has now embraced the call for a cure and it has become one of his top research priorities.
When California voters approved Proposition 71 seven years ago, none of us knew where the science might lead. And one cannot promise a specific cure for HIV or any other disease. However, I know that the existence of CIRM has greatly helped to change the research agenda for HIV globally and I suspect this is true for many other diseases and conditions.
CIRM, the California stem cell institute, does not propose temporary or episodic relief from disease, pain and suffering. We are committed to finding cures and we are working towards them relentlessly in partnership with patients, researchers and industry across California. This year on World AIDS Day, 30 long years into the HIV/AIDS epidemic, CIRM is a beacon of hope.
This video features Jeff Sheehy and CIRM disease team leader talking about a CIRM-funded project for HIV/AIDS:
J.S.
CIRM helping stem cell scientists and investors pair up
In La Jolla, stem cell scientists, companies and investors are engaging in a series of CIRM-sponsored get-to-know-you meetings as part of the first ever partnering forum in conjunction with the annual Stem Cell Meeting on the Mesa. These meetings are part of CIRM's ramped-up efforts to help scientists overcome obstacles on the path to clinical trials.
Elona Baum, CIRM General Counsel and Vice President of Business Development, was one of the primary organizers of the Investor and Partnering Forum. She said:
Forming the partnerships that will allow academic researchers and researchers at young biotech firms to see their work eventually reach clinical trials is what the La Jolla meetings are all about. It's a chance for stem cell researchers to pitch their work to investors in the hopes of finding a good fit. They can also attend a series of sessions about how to navigate the regulatory pathway and form collaborations, among other sessions.
This forum is one of several ways CIRM is trying to help academic scientists succeed in getting their research translated into therapies. CIRM continues to hold conversations, roundtables and webinars with the FDA, the agency regulating investigational products and whether and when they can enter clinical trials. By having conversations now, CIRM can help researchers meet FDA requirements enabling them to enter their products into clinical trials. CIRM’s webinars to inform its grantees about different areas of stem cell research and the regulatory path are also publicly available to view on the CIRM website.
A.A.
Elona Baum, CIRM General Counsel and Vice President of Business Development, was one of the primary organizers of the Investor and Partnering Forum. She said:
"The forum will feature company presentations and industry discussion panels on regulatory, finance, commercialization and reimbursement issues. The Forum will provide the opportunity for hundreds of business, academic research and investor participants to connect for one-on-one meetings and strategic partnering."CIRM has 43 projects in various stages of working toward clinical trials (more information about those projects is available here). Getting from their current status through clinical trials will require significant investment. It takes big money to gather the kind of preclinical data the Food and Drug Administration (FDA) needs to see before allowing a product to enter first-in-human clinical trials. CIRM funds preclinical through early phase clinical trials, but researchers in academia also need to seek funding from other sources to gather sufficient data, and engage industry partners early to help carry their work into the clinic and the subsequent development steps towards regulatory approval.
Forming the partnerships that will allow academic researchers and researchers at young biotech firms to see their work eventually reach clinical trials is what the La Jolla meetings are all about. It's a chance for stem cell researchers to pitch their work to investors in the hopes of finding a good fit. They can also attend a series of sessions about how to navigate the regulatory pathway and form collaborations, among other sessions.
This forum is one of several ways CIRM is trying to help academic scientists succeed in getting their research translated into therapies. CIRM continues to hold conversations, roundtables and webinars with the FDA, the agency regulating investigational products and whether and when they can enter clinical trials. By having conversations now, CIRM can help researchers meet FDA requirements enabling them to enter their products into clinical trials. CIRM’s webinars to inform its grantees about different areas of stem cell research and the regulatory path are also publicly available to view on the CIRM website.
A.A.
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