Science is full of acronyms. There are days where it feels like you need a decoder ring just to understand a simple sentence. A recent study found that between 1950 and 2019 researchers used more than 1.1 million unique acronyms in scientific papers. There’s even an acronym for three letter acronyms. It’s TLAs. Which of course has one more letter than the thing it stands for.
I only mention this because I just learned a new acronym, but this one could help change the way we are able to study causes of infertility. The acronym is IVG or in vitro gametogenesis and it could enable scientists to create both sperm and egg, from stem cells, and grow them in the lab. And now scientists in Japan have done just that and allowed these fertilized eggs to then develop into mice.
The study, published in the journal Science, was led by Dr. Katsuhiko Hayashi of Kyushu University in Japan. Dr. Hayashi is something of a pioneer in the field of IVG. In the past his team were the first to produce both mouse sperm, and mouse eggs from stem cells. But they ran into a big obstacle when they tried to get the eggs to develop to a point where they were ready to be fertilized.
Over the last five years they have worked to find a way around this obstacle and, using mouse embryonic stem cells, they developed a process to help these stem cell-generated eggs mature to the point where they were viable.
In an article in STAT News Richard Anderson, Chair of Clinical Reproductive Science at the University of Edinburgh, said this was a huge achievement: “It’s a very serious piece of work. This group has done a lot of impressive things leading up to this, but this latest paper really completes the in vitro gametogenesis story by doing it in a completely stem-cell-derived way.”
The technique could prove invaluable in helping study infertility in people and, theoretically, could one day lead to women struggling with infertility to be able to use their own stem cells to create eggs or men their own sperm. However, the researchers say that even if that does become possible it’s likely a decade or more away.
While the study is encouraging on a scientific level, it’s raising some concerns on an ethical level. Should there be limits on how many of these manufactured embryos that a couple can create? Can someone create dozens or hundreds of these embryos and then sift through them, using genetic screening tools, to find the ones that have the most desirable traits?
One thing is clear, while the science is evolving, bioethicists, scholars and the public need to be discussing the implications for this work, and what kinds of restraints, if any, need to be applied before it’s RFPT (ready for prime time – OK, I made that one up.)
If you have never heard of AADC deficiency count yourself lucky. It’s a rare, incurable condition that affects only around 135 children worldwide but it’s impact on those children and their families is devastating. The children can’t speak, can’t feed themselves or hold up their head, they have severe mood swings and often suffer from insomnia.
But Dr. Krystof Bankiewicz, a doctor and researcher at the University of California San Francisco (UCSF), is using techniques he developed treating Parkinson’s disease to help those children. Full disclosure here, CIRM is funding Dr. Bankiewicz’s Parkinson’s clinical trial.
In AADC deficiency the children lack a critical enzyme that helps the brain make serotonin and dopamine, so called “chemical messengers” that help the cells in the brain communicate with each other. In his AADC clinical trial Dr. Bankiewicz and his team created a tiny opening in the skull and then inserted a functional copy of the AADC gene into two regions of the brain thought to have most benefit – the substantia nigra and ventral tegmental area of the brainstem.
When the clinical trial began none of the seven children were able to sit up on their own, only two had any ability to control their head movement and just one could grasp an object in their hands. Six of the seven were described as moody or irritable and six suffered from insomnia.
In a news release Dr. Bankiewicz says the impact of the gene therapy was quite impressive: “Remarkably, these episodes were the first to disappear and they never returned. In the months that followed, many patients experienced life-changing improvements. Not only did they begin laughing and have improved mood, but some were able to start speaking and even walking.”
Those weren’t the only improvements, at the end of one year:
All seven children had better control of their head and body.
Four of the children were able to sit up by themselves.
Three patients could grasp and hold objects.
Two were able to walk with some support.
Two and a half years after the surgery:
One child was able to walk without any support.
One child could speak with a vocabulary of 50 words.
One child could communicate using an assistive device.
The parents also reported big improvements in mood and ability to sleep.
UCSF posted some videos of the children before and after the surgery and you can see for yourself the big difference in the children. It’s not a cure, but for families that had nothing in the past, it is a true gift.
Transplanting cells or an entire organ from one person to another can be lifesaving but it comes with a cost. To avoid the recipient’s body rejecting the cells or organ the patient has to be given powerful immunosuppressive medications. Those medications weaken the immune system and increase the risk of infections. But now a team at the University of California San Francisco (UCSF) have used a new kind of stem cell to find a way around that problem.
The cells are called HIP cells and they are a specially engineered form of induced pluripotent stem cell (iPSC). Those are cells that can be turned into any kind of cell in the body. These have been gene edited to make them a kind of “universal stem cell” meaning they are not recognized by the immune system and so won’t be rejected by the body.
The UCSF team tested these cells by transplanting them into three different kinds of mice that had a major disease; peripheral artery disease; chronic obstructive pulmonary disease; and heart failure.
The results, published in the journal Proceedings of the National Academy of Science, showed that the cells could help reduce the incidence of peripheral artery disease in the mice’s back legs, prevent the development of a specific form of lung disease, and reduce the risk of heart failure after a heart attack.
In a news release, Dr. Tobias Deuse, the first author of the study, says this has great potential for people. “We showed that immune-engineered HIP cells reliably evade immune rejection in mice with different tissue types, a situation similar to the transplantation between unrelated human individuals. This immune evasion was maintained in diseased tissue and tissue with poor blood supply without the use of any immunosuppressive drugs.”
Deuse says if this does work in people it may not only be of great medical value, it may also come with a decent price tag, which could be particularly important for diseases that affect millions worldwide.
“In order for a therapeutic to have a broad impact, it needs to be affordable. That’s why we focus so much on immune-engineering and the development of universal cells. Once the costs come down, the access for all patients in need increases.”
At first glance Lauren Miller Rogen and Dr. David Higgins seem an unlikely pair. She’s an actor, writer, director and has worked with some of the biggest names in Hollywood. He has a doctorate in molecular biology and genetics and has worked at some of the most well-known companies in biotech. But together they make a great team.
Lauren and David are both on the CIRM Board. She’s a patient advocate for Alzheimer’s and the driving force (with her husband Seth) of HFC (Hilarity for Charity), which has raised millions of dollars to help families battling the disease and to educate young people about the condition. It’s also made a lot of people laugh along the way. David is a patient advocate for Parkinson’s and has been instrumental is creating support groups that help patients and families cope with the disease.
When the voters of California approved Proposition 14 last November (thanks folks) they gave us $5.5 billion to continue the work we started way back in 2014. It’s a great honor, and a great responsibility.
It’s also a great opportunity to look at what we do and how we do it and try to come up with even better ways of funding groundbreaking research and helping create a new generation of researchers.
In addition to improving on what we already do, Prop 14 introduced some new elements, some new goals for us to add to the mix, and we are in the process of fleshing out how we can best do that.
Because of all these changes we decided it would be a good idea to hold a “Town Hall” meeting and let everyone know what these changes are and how they may impact applications for funding.
The Town Hall, on Tuesday June 29, was a great success with almost 200 participants. But we know that not everyone who wanted to attend could, so here’s the video of the event, and below that are the questions that were posed by people during the meeting, and the answers to those questions.
Having seen the video we would be eternally grateful if you could respond to a short online survey, to help us get a better idea of your research and education needs and to be better able to serve you and identify potential areas of opportunity for CIRM. Here’s a link to that survey: https://www.surveymonkey.com/r/VQMYPDL
We know that there may be issues or questions that are not answered here, so feel free to send those to us at email@example.com and we will make sure you get an answer.
Are there any DISC funding opportunities specific to early-stage investigators?
DISC funding opportunities are open to all investigators. There aren’t any that are specific to junior investigators.
Are DISC funding opportunities available for early-mid career researchers based out of USA such as Australia?
Sorry, you have to be in California for us to fund your work.
Does tumor immunology/ cancer immunotherapy fall within the scope of the CIRM discovery grants?
CIRM funding supports non-profit academic grantees as well as companies of all sizes.
I am studying stem cells using mouse. Is my research eligible for the CIRM grants?
Yes it is.
Your programs more specifically into stem cell research would be willing to take patients that are not from California?
Yes, we have treated patients who are not in California. Some have come to California for treatment and others have been treated in other states in the US by companies that are based here in California.
Can you elaborate how the preview of the proposals works? Who reviews them and what are the criteria for full review?
The same GWG panel both previews and conducts the full review. The panel first looks through all the applications to identify what each reviewer believes represents the most likely to be impactful and meet the goals of the CIRM Discovery program. Those that are selected by any reviewer moves forward to the next full review step.
If you meet your milestones-How likely is it that a DISC recipient gets a TRAN award?
The milestones are geared toward preparation of the TRAN stage. However, this is a different application and review that is not guaranteed to result in funding.
Regarding Manufacturing Public Private partnerships – What specific activities is CIRM thinking about enabling these partnerships? For example, are out of state for profit commercial entities able to conduct manufacturing at CA based manufacturing centers even though the clinical program may be primarily based out of CA? If so, what percent of the total program budget must be expended in CA? How will CIRM enable GMP manufacturing centers interact with commercial entities?
We are in the early stages of developing this concept with continued input from various stakeholders. The preliminary vision is to build a network of academic GMP manufacturing centers and industry partners to support the manufacturing needs of CIRM-funded projects in California.
We are in the process of widely distributing a summary of the manufacturing workshop. Here’s a link to it:
If a center is interested in being a sharing lab or competency hub with CIRM, how would they go about it?
CIRM will be soliciting applications for Shared Labs/Competency hubs in potential future RFAs. The survey asks several questions asking for feedback on these concepts so it would really help us if you could complete the survey.
Would preclinical development of stem cell secretome-derived protein therapies for rare neuromuscular diseases and ultimately, age-related muscle wasting be eligible for CIRM TRAN1 funding? The goal is to complete IND-enabling studies for a protein-based therapy that enhances tissue regeneration to treat a rare degenerative disease. the screening to identify the stem-cell secreted proteins to develop as therapeutics is done by in vitro screening with aged/diseased primary human progenitor cells to identify candidates that enhance their differentiation . In vivo the protein therapeutic signals to several cell types , including precursor cells to improve tissue homeostasis.
I would suggest reaching out to our Translation team to discuss the details as it will depend on several factors. You can email the team at firstname.lastname@example.org
There are many unknown elements for what triggers the cells in an embryo to start dividing and multiplying and becoming every single cell in the body. Now researchers at the Gladstone Institutes in San Francisco have uncovered one of those elements, how embryos determine which cells become the head and which the tail.
In this CIRM-funded study the Gladstone team, led by Dr. Todd McDevitt, discovered almost by chance how the cells align in a heads-to-tail arrangement.
They had created an organoid made from brain cells when they noticed that some of the cells were beginning to gather in an elongated fashion, in the same way that spinal cords do in a developing fetus.
In a news article, Nick Elder, a graduate student at Gladstone and the co-author of the study, published in the journal Development, says this was not what they had anticipated would happen: “Organoids don’t typically have head-tail directionality, and we didn’t originally set out to create an elongating organoid, so the fact that we saw this at all was very surprising.”
Further study enabled the team to identify which molecules were involved in signaling specific genes to switch on and off. These were similar to the process previously identified in developing mouse embryos.
“This is such a critical point in the early development of any organism, so having a new model to observe it and study it in the lab is very exciting,” says McDevitt.
This is not just of academic interest either, it could have real world implications in helping understand what causes miscarriages or birth defects.
“We can use this organoid to get at unresolved human developmental questions in a way that doesn’t involve human embryos,” says Dr. Ashley Libby, another member of the team. “For instance, you could add chemicals or toxins that a pregnant woman might be exposed to, and see how they affect the development of the spinal cord.”
When Proposition 14 was approved by voters in November we were given a chance to carry on the work we have been doing for more than 16 years. What we hadn’t anticipated was that we would also get a chance to do that with some of the team that helped us make CIRM what it is, but who had since moved on to other jobs.
We are delighted to say that as we build up our team again we are welcoming back a couple of dear friends, and welcoming in some new ones too. They’re a talented bunch and, if they don’t mind me saying so, a darned good looking group too.
Rosa Canet-Aviles, PhD., has been named as the new Vice President Scientific Programs. Rosa is a familiar face at the agency, serving as a Science Officer with CIRM from 2008 to 2014. During that time she helped oversee the development of our Translational program, managed a broad portfolio of projects and organized workshops on Parkinson’s and autism.
After leaving CIRM she joined the Foundation for the National Institutes of Health (FINH) where she served as the Director of Neuroscience Research Partnerships. In that role she led the successful development and management of 5 new large partnerships including the Biomarkers Consortium Neuroscience Steering Committee, the Accelerating Medicines Partnership (AMP) for Alzheimer’s disease 1.0 and 2.0, AMP Parkinson’s disease and AMP Schizophrenia.
Rosa has more than 15 years of experience working in industry, academia and government and her experience in developing and managing neuroscience programs will be invaluable as CIRM looks to invest some $1.5 billion in neuroscience under Proposition 14.
“I am very excited to be back,” says Rosa. ”It is a dream come true being able to translate all the skills, learning and networks gathered over the past 7 years towards the development and implementation of CIRM’s new phase and accelerate stem cell therapies for patients in need.”
“We are thrilled to announce the timely return of Rosa to CIRM as we build our new strategic plan under Prop 14,” says Dr. Maria T. Millan, CIRM’s President & CEO. “Rosa has demonstrated time and again the unique ability to bring together often seemingly disparate stakeholders to successfully drive toward a common goal of advancing the science on behalf of patients with diseases of the brain and neuropsychiatric disorders. At CIRM, she assembled key international leaders who went on to form an international Parkinson’s Disease consortium. At the Foundation for NIH (FNIH), she directed the development of five prominent public-private partnerships. A neuroscientist by training, she is held in high regard and has been called a “quick study” in her ability to lead in new areas such as in genomics and data science, key components of her role at FNIH and at Eisai’s Center for Genetics Guided Dementia Discovery.“
In addition, CIRM is pleased to announce the following new team members:
Uta Grieshammer, PhD. is also returning to CIRM as the Senior Science Officer for our Discovery program. Uta was at CIRM from 2007 to 2015 and led the programs that created both our Genomics Initiative and our iPSC bank. She also organized several scientific conferences and workshops involving hundreds of CIRM-funded researchers.
After leaving CIRM she became the Scientific Director of the California Initiative to Advance Precision Medicine at the University of California San Francisco where she created and managed the application and peer review process. Most recently she was the Program Officer at the University of California Office of the President’s (UCOP) Tobacco Related Disease Research Program where she focused on the neuroscience of nicotine addiction. She also helped develop a scholarship program to attract students from diverse backgrounds to pursue a career in science.
Michael Bunch joins CIRM as a Business Service Officer. Michael is a decorated veteran who has been working as the Chief Business Officer at the Veterans Home in Yountville, California. In that role he implemented new contract and reviewing processes and oversaw the income and insurance tracking for some 1,000 residents. With his extensive background in acquisition management, contingency contracting, and his deep knowledge of state regulations and guidelines Michael was able to increase funding, streamline processes and assist Veterans and their families to obtain the benefits and services that they qualified for.
Michael spent 25 years in the US Army including serving as part of the NATO peacekeeping force in Kosovo. During that deployment he was awarded the Joint Service Commendation Medal (JSCM) for managing the fuel needs of 4 Multinational Task Forces and 33 Nations, an essential element in helping the mission succeed.
A Senior Drill Sergeant, Infantry Instructor and Financial and Resource Manager Michael has been awarded the Army Commendation Medal with 4 Oak Leaves, Army Achievement Medal with 4 Oak Leaves, Global War on Terrorism Service Medal, KOSOVO Campaign Medal, Military Outstanding Volunteer Service Medal, NATO Medal, Expert Infantryman Badge, Honorary Kentucky Colonel and Honorary Kentucky Admiral.
Nellie Almazan joins CIRM as a Grants Management Specialist. Nellie comes to us from the California Department of Transportation (Caltrans) where she has worked for 16 years, most recently as the Associate Transportation Planner with the Low Carbon Transit Operations program. Nellie managed more than 150 projects, reviewing grants to help reduce greenhouse gas emissions in the state and overseeing programs that had an emphasis on serving Disadvantaged Communities.
She is currently enrolled at Sacramento City College where her focus is on Sociology and Deaf Culture.
Alexandra Caraballo joins CIRM as a Grants Management Specialist. Alex has more than 15 years of grant administration experience with a focus on incorporating equity, diversity, and inclusion into grantmaking practices and decision-making. She comes to CIRM from the Kaiser Foundation Health Plan where she was the National Manager of Philanthropy. There she was responsible for the administration of approximately 200 grants in the national community health portfolio. Before Kaiser she was the Program Assistant and Associate Program Officer at the East Bay Community Foundation, where she partnered with donors and community-based organizations to advance racial equity and transform political, social and economic outcomes for East Bay Communities.
Alex currently serves on the Board of Directors for the Lindsay Wildlife Experience and was a former Advisory Board member for Oakland Head Start.
Over the last year there has been increasing awareness of the inequalities in the American healthcare system. At every level there is evidence of bias, discrimination and unequal access to the best care. Sometimes unequal access to any care. That is, hopefully, changing but only if the new awareness is matched with action.
At the recent World Stem Cell Summit CIRM helped pull together a panel of physicians and patient advocates who have been leading the charge for change for years. The panel was called ‘Addressing Disparities, Promoting Equity and Inclusion in Clinical Research.’
The panelists include:
The conversation they had was informative, illuminating and fascinating. But it didn’t sugar coat where we are, and the hard work ahead of us to get to where we need to be.
Enjoy the event, with apologies for the inept cameo appearance by me at the beginning of the video. Technology clearly isn’t my forte.
World Sickle Cell Day is this Saturday June 19th. The goal of this day is to increase knowledge of the disease and understanding of the challenges faced.
It is a day that I greet with very mixed feelings. I’m of course extremely grateful to CIRM for the time and money spent looking for a cure. The work of doctors, of researchers, the courage of families in the sickle cell community who are taking part in studies, and of course those of you who worked so hard for the original funding for CIRM, I applaud all of you, yet it’s hard to wait for a cure.
While I wait I worry. I worry about my friends who are not getting good care. They are the ones who can’t find a doctor to treat them, not able to take advantage of the medications that are already approved. They are the ones who walk into the Emergency Room hoping for knowledgeable treatment while understanding that they may be accused of being a drug seeker, turned away in excruciating pain. They are the ones who succumb after years of poor care.
With sickle cell disease there is the same level of understanding about medical malpractice that we had of police brutality before George Floyd. We hardly remember Rodney King or Eric Garner. As a country we were aware that something was wrong but we tended to retreat in denial after each terrible headline.
That’s where we are with sickle cell disease. We may see a heart-wrenching story and watch televised reports with interest, but after all, it’s easier to live in disbelief, to think that medical care is not that bad, rather than understand that people are being dismissed and denied treatment. We call it structural racism without understanding what that term really means.
While I wait I must acknowledge that change is coming. We have a Sickle Cell Data Collection Project in California that helps us track healthcare for sickle cell disease. This is data that we can use to point to structural weakness and address health disparities. NASEM, the National Academies of Science Engineering and Medicine, has published a huge report with significant suggestions for improving sickle cell care. Many scientists, researchers and advocates took part in this landmark study, detailing what has gone wrong in health care and how to improve the work. And of course we have CIRM. I am very thankful for the leadership and pioneering work of doctors Donald Kohn, Matthew Porteus, Mark Walters, and Joseph Rosenthal who are using their knowledge and experience in this fight.
When we have successful research on stem cell transplants for sickle cell disease, many of us with sickle cell family members will want to relax, but we can’t forget those who may not be able to get a curative transplant. I hope Dr Niihara at Emmaus, and Dr. Love of Global Blood Therapeutics will continue their important work finding effective treatments. We must continue this fight on all fronts.
World Sickle Cell Day will come again next year. Let’s see what it brings.
Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in the elderly in the U.S. It’s estimated that some 11 million Americans could have some form of the disease, a number that is growing every year. So if you are going to develop a treatment for this condition, you need to make sure it can reach a lot of people easily. And that’s exactly what some CIRM-supported researchers are doing.
Let’s back up a little first. AMD is a degenerative condition where the macular, the small central portion of your retina, is slowly worn away. That’s crucial because the retina is the light-sensing nerve tissue at the back of your eye. At first you notice that your vision is getting blurry and it’s hard to read fine print or drive a car. As it progresses you develop dark, blurry areas in the center of your vision.
There are two kinds of AMD, a wet form and a dry form. The dry form is the most common, affecting 90% of patients. There is no cure and no effective treatment. But researchers at the University of Southern California (USC), the University of California Santa Barbara (UCSB) and a company called Regenerative Patch Technologies are developing a method that is looking promising.
They are using stem cells to grow retinal pigment epithelium (RPE) cells, the kind attacked by the disease, and putting them on a tiny synthetic scaffold which is then placed at the back of the eye. The hope is these RPE cells will help slow down the progression of the disease or even restore vision.
Early results from a CIRM-funded clinical trial are encouraging. Of the five patients enrolled in the Phase 1/2a trial, four maintained their vision in the treated eye, two showed improvement in the stability of their vision, and one patient had a 17-letter improvement in their vision on a reading chart. In addition, there were no serious side effects or unanticipated problems.
So now the team are taking this approach one step further. In a study published in Scientific Reports, they say they have developed a way to cryopreserve or freeze this cell and scaffold structure.
In a news release, Dr. Dennis Clegg of UCSB, says the frozen implants are comparable to the non-frozen ones and this technique will extend shelf life and enable on-demand distribution to distant clinical sites, increasing the number of patients able to benefit from such treatments.
“It’s a major advance in the development of cell therapies using a sheet of cells, or a monolayer of cells, because you can freeze them as the final product and ship them all over the world.”