We were saddened to learn today of the death of Susan Solomon, the CEO and co-founder of the New York Stem Cell Foundation (NYSCF), a non-profit organization that supports stem cell research around the world. As CEO, Ms. Solomon raised over $400M for stem cell research, helping to catalyze the field and transform the future of medical research.
The foundation announced the news on its website, saying she died after a long battle with ovarian cancer.
CIRM’s Chair Jonathan Thomas said she will be greatly missed. “We were so terribly sorry to hear about Susan’s passing. She was a titan in our field who did immeasurable good for patients everywhere. We have so valued our relationship with her and NYSCF through the years.”
Like many patient advocates Ms. Solomon became active when a family member was hit by disease. In her case, it was in 1992 when her ten year old son Ben was diagnosed with type 1 diabetes. A lawyer by training and a longtime business executive she put her skills to work to identify the best way to help her son, and others with type 1 diabetes. In an interview in the Wall Street Journal she says that background really helped: “As a lawyer, you learn how to learn about a new field instantly,” and, she added, “I’m really comfortable asking dumb questions.”
After much research and many conversations with scientists she concluded that stem cells were the most promising way to help patients. In 2005 she co-founded NYSCF.
Dr. Jeanne Loring, the Director of the Center for Regenerative Medicine at the Scripps Research Institute, says Ms. Solomon’s death is a huge blow to the field: “I have worked with NYSCF for the last 5 years, on the project to study neuroinflammation in space using iPSC-derived neurons. Susan was one in a billion, she threw all of her considerable energy into starting and sustaining the only stand-alone research institute that I know of in the US dedicated to stem cell research.”
A few weeks ago we held a Facebook Live “Ask the Stem Cell Team About Parkinson’s Disease” event. As you can imagine we got lots of questions but, because of time constraints, only had time to answer a few. Thanks to my fabulous CIRM colleagues, Dr. Lila Collins and Dr. Kent Fitzgerald, for putting together answers to some of the other questions. Here they are.
Kent Fitzgerald, PhD
Q:It seems like we have been hearing for years that stem cells can help people with Parkinson’s, why is it taking so long?
A: Early experiments in Sweden using fetal tissue did provide a proof of concept for the strategy of replacing dopamine producing cells damaged or lost in Parkinson’s disease (PD) . At first, this seemed like we were on the cusp of a cell therapy cure for PD, however, we soon learned based on some side effects seen with this approach (in particular dyskinesias or uncontrollable muscle movements) that the solution was not as simple as once thought.
While this didn’t produce the answer it did provide some valuable lessons.
The importance of dopaminergic (DA) producing cell type and the location in the brain of the transplant. Simply placing the replacement cells in the brain is not enough. It was initially thought that the best site to place these DA cells is a region in the brain called the SN, because this area helps to regulate movement. However, this area also plays a role in learning, emotion and the brains reward system. This is effectively a complex wiring system that exists in a balance, “rewiring” it wrong can have unintended and significant side effects.
Another factor impacting progress has been understanding the importance of disease stage. If the disease is too advanced when cells are given then the transplant may no longer be able to provide benefit. This is because DA transplants replace the lost neurons we use to control movement, but other connected brain systems have atrophied in response to losing input from the lost neurons. There is a massive amount of work (involving large groups and including foundations like the Michael J Fox Foundation) seeking to identify PD early in the disease course where therapies have the best chance of showing an effect. Clinical trials will ultimately help to determine the best timing for treatment intervention.
Ideally, in addition to the cell therapies that would replace lost or damaged cells we also want to find a therapy that slows or stops the underlying biology causing progression of the disease.
So, I think we’re going to see more gene therapy trials including those targeting the small minority of PD that is driven by known mutations. In fact, Prevail Therapeutics will soon start a trial in patients with GBA1 mutations. Hopefully, replacing the enzyme in this type of genetic PD will prevent degeneration.
And, we are also seeing gene therapy approaches to address forms of PD that we don’t know the cause, including a trial to rescue sick neurons with GDNF which is a neurotrophic factor (which helps support the growth and survival of these brain cells) led by Dr Bankiewicz and trials by Axovant and Voyager, partnered with Neurocrine aimed at restoring dopamine generation in the brain.
A small news report came out earlier this year about a recently completed clinical trial by Roche Pharma and Prothena. This addressed the build up in the brain of what are called lewy bodies, a problem common to many forms of PD. While the official trial results aren’t published yet, a recent press release suggests reason for optimism. Apparently, the treatment failed to statistically improve the main clinical measurement, but other measured endpoints saw improvement and it’s possible an updated form of this treatment will be tested again in the hopes of seeing an improved effect.
Finally, I’d like to call attention to the G force trials. Gforce is a global collaborative effort to drive the field forward combining lessons learned from previous studies with best practices for cell replacement in PD. These first-in-human safety trials to replace the dopaminergic neurons (DANs) damaged by PD have shared design features including identifying what the best goals are and how to measure those.
And the Summit PD trial, Dr Jeanne Loring of Aspen Neuroscience.
Taken together these should tell us quite a lot about the best way to replace these critical neurons in PD.
As with any completely novel approach in medicine, much validation and safety work must be completed before becoming available to patients
The current approach (for cell replacement) has evolved significantly from those early studies to use cells engineered in the lab to be much more specialized and representing the types believed to have the best therapeutic effects with low probability of the side effects (dyskinesias) seen in earlier trials.
If we don’t really know the cause of Parkinson’s disease, how can we cure it or develop treatments to slow it down?
PD can now be divided into major categories including 1. Sporadic, 2. Familial.
For the sporadic cases, there are some hallmarks in the biology of the neurons affected in the disease that are common among patients. These can be things like oxidative stress (which damages cells), or clumps of proteins (like a-synuclein) that serve to block normal cell function and become toxic, killing the DA neurons.
The second class of “familial” cases all share one or more genetic changes that are believed to cause the disease. Mutations in genes (like GBA, LRRK2, PRKN, SNCA) make up around fifteen percent of the population affected, but the similarity in these gene mutations make them attractive targets for drug development.
CIRM has funded projects to generate “disease in a dish” models using neurons made from adults with Parkinson’s disease. Stem cell-derived models like this have enabled not only a deep probing of the underlying biology in Parkinson’s, which has helped to identify new targets for investigation, but have also allowed for the testing of possible therapies in these cell-based systems.
iPSC-derived neurons are believed to be an excellent model for this type of work as they can possess known familial mutations but also show the rest of the patients genetic background which may also be a contributing factor to the development of PD. They therefore contain both known and unknown factors that can be tested for effective therapy development.
I have heard of scientists creating things called brain organoids, clumps of brain cells that can act a little bit like a brain. Can we use these to figure out what’s happening in the brain of people with Parkinson’s and to develop treatments?
There is considerable excitement about the use of brain organoids as a way of creating a model for the complex cell-to-cell interactions in the brain. Using these 3D organoid models may allow us to gain a better understanding of what happens inside the brain, and develop ways to treat issues like PD.
The organoids can contain multiple cell types including microglia which have been a hot topic of research in PD as they are responsible for cleaning up and maintaining the health of cells in the brain. CIRM has funded the Salk Institute’s Dr. Fred Gage’s to do work in this area.
If you go online you can find lots of stem cells clinics, all over the US, that claim they can use stem cells to help people with Parkinson’s. Should I go to them?
In a word, no! These clinics offer a wide variety of therapies using different kinds of cells or tissues (including the patient’s own blood or fat cells) but they have one thing in common; none of these therapies have been tested in a clinical trial to show they are even safe, let alone effective. These clinics also charge thousands, sometimes tens of thousands of dollars these therapies, and because it’s not covered by insurance this all comes out of the patient’s pocket.
These predatory clinics are peddling hope, but are unable to back it up with any proof it will work. They frequently have slick, well-designed websites, and “testimonials” from satisfied customers. But if they really had a treatment for Parkinson’s they wouldn’t be running clinics out of shopping malls they’d be operating huge medical centers because the worldwide need for an effective therapy is so great.
Here’s a link to the page on our website that can help you decide if a clinical trial or “therapy” is right for you.
Is it better to use your own cells turned into brain cells, or cells from a healthy donor?
This is the BIG question that nobody has evidence to provide an answer to. At least not yet.
Let’s start with the basics. Why would you want to use your own cells? The main answer is the immune system. Transplanted cells can really be viewed as similar to an organ (kidney, liver etc) transplant. As you likely know, when a patient receives an organ transplant the patient’s immune system will often recognize the tissue/organ as foreign and attack it. This can result in the body rejecting what is supposed to be a life-saving organ. This is why people receiving organ transplants are typically placed on immunosuppressive “anti-rejection “drugs to help stop this reaction.
In the case of transplanted dopamine producing neurons from a donor other than the patient, it’s likely that the immune system would eliminate these cells after a short while and this would stop any therapeutic benefit from the cells. A caveat to this is that the brain is a “somewhat” immune privileged organ which means that normal immune surveillance and rejection doesn’t always work the same way with the brain. In fact analysis of the brains collected from the first Swedish patients to receive fetal transplants showed (among other things) that several patients still had viable transplanted cells (persistence) in their brains.
Transplanting DA neurons made from the patient themselves (the iPSC method) would effectively remove this risk of the immune system attack as the cells would not be recognized as foreign.
CIRM previously funded a discovery project with Jeanne Loring from Scripps Research Institute that sought to generate DA neurons from Parkinson’s patients for use as a potential transplant therapy in these same patients. This project has since been taken on by a company formed, by Dr Loring, called Aspen Neuroscience. They hope to bring this potential therapy into clinical trials in the near future.
A commonly cited potential downside to this approach is that patients with genetic (familial) Parkinson’s would be receiving neurons generated with cells that may have the same mutations that caused the problem in the first place. However, as it can typically take decades to develop PD, these cells could likely function for a long time. and prove to be better than any current therapies.
Creating cells from each individual patient (called autologous) is likely to be very expensive and possibly even cost-prohibitive. That is why many researchers are working on developing an “off the shelf” therapy, one that uses cells from a donor (called allogeneic)would be available as and when it’s needed.
When the coronavirus happened, it seemed as if overnight the FDA was approving clinical trials for treatments for the virus. Why can’t it work that fast for Parkinson’s disease?
While we don’t know what will ultimately work for COVID-19, we know what the enemy looks like. We also have lots of experience treating viral infections and creating vaccines. The coronavirus has already been sequenced, so we are building upon our understanding of other viruses to select a course to interrupt it. In contrast, the field is still trying to understand the drivers of PD that would respond to therapeutic targeting and therefore, it’s not precisely clear how best to modify the course of neurodegenerative disease. So, in one sense, while it’s not as fast as we’d like it to be, the work on COVID-19 has a bit of a head start.
Much of the early work on COVID-19 therapies is also centered on re-purposing therapies that were previously in development. As a result, these potential treatments have a much easier time entering clinical trials as there is a lot known about them (such as how safe they are etc.). That said, there are many additional therapeutic strategies (some of which CIRM is funding) which are still far off from being tested in the clinic.
The concern of the Food and Drug Administration (FDA) is often centered on the safety of a proposed therapy. The less known, the more cautious they tend to be.
As you can imagine, transplanting cells into the brain of a PD patient creates a significant potential for problems and so the FDA needs to be cautious when approving clinical trials to ensure patient safety.
Students present their research finding at the 2016 CIRM Bridges conference
One of the programs people here at CIRM love is our Bridges to Stem Cell Research Awards. These are given to undergraduate and master’s level college students, to train the next generation of stem cell scientists. How good a program is it? It’s terrific. You don’t have to take my word for it. Just read this piece by a great stem cell champion, Don Reed. Don is the author of two books about CIRM, Stem Cell Battles and California Cures! so he clearly knows what he’s talking about.
ADVENTURES ON “BRIDGES”: Humboldt State Stem Cell Research
By Don C. Reed
Imagine yourself as a California college student, hoping to become a stem cell researcher. Like almost all students you are in need of financial help, and so (let’s say) you asked your college counselor if there were any scholarships available.
To your delight, she said, well, there is this wonderful internship program called Bridges, funded by the California Institution for Regenerative Medicine (CIRM) which funds training in stem cell biology and regenerative medicine — and so, naturally, you applied…
After doing some basic training at the college, you would receive a grant (roughly $40,000) for a one-year internship at a world-renowned stem cell research facility. What an incredible leap forward in your career, hands-on experience (essentially a first job, great “experience” for the resume) as well an expert education.
Where are the 14 California colleges participating in this program? Click below:
Let’s take a look at one of these college programs in action: find out what happened to a few of the students who received a Bridges award, crossing the gap between studying stem cell research and actually applying it.
HSU information is courtesy of Dr. Amy Sprowles, Associate Professor of Biological Sciences and Co-Director of the Bridges program at Humboldt State University (HSU), 279 miles north of San Francisco.
Dr. Amy Sprowles
“The HSU Bridges program”, says Dr. Sprowles, “was largely developed by four people: Rollin Richmond, then HSU President, who worked closely with Susan Baxter, Executive Director of the CSU Program for Education and Research in Biotechnology, to secure the CIRM Bridges initiative; HSU Professor of Biological Sciences Jacob Varkey, who pioneered HSU’s undergraduate biomedical education program”, and Sprowles herself, at the time a lecturer with a PhD in Biochemistry.
The program has two parts: a beginning course in stem cell research, and a twelve-month internship in a premiere stem cell research laboratory. For HSU, these are at Stanford University, UC Davis, UCSF, or the Scripps Research Institute.
Like all CIRM Bridges programs, the HSU stem cell program is individually designed to suit the needs of its community.
Each of the 15 CIRM Bridges Programs fund up to ten paid internships, but the curriculum and specific activities of each are designed by their campus directors. The HSU program prepares Bridges candidates by requiring participation in a semester-long lecture and stem cell biology laboratory course before selection for the program: a course designed and taught by Sprowles since its inception.
She states, “The HSU pre-internship course ensures our students are trained in fundamental scientific concepts, laboratory skills and professional behaviors before entering their host laboratory. We find this necessary since, unlike the other Bridges campuses, we are 300+ miles away from the internship sites and are unable to fully support this kind of training during the experience. It also provides additional insights about the work ethic and mentoring needs of the individuals we select that are helpful in placing and supporting our program participants”.
How is it working?
Ten years after it began, 76 HSU students have completed the CIRM Bridges program at HSU. Of those, the overwhelming majority (over 85%) are committed to careers in regenerative medicine: either working in the field already, or continuing their education toward that goal.
But what happened to their lives? Take a brief look at the ongoing careers of a “Magnificent Seven” HSU Bridges scientists:
CARSTEN CHARLESWORTH: “Spurred by the opportunity to complete a paid internship at a world class research institution in Stem Cell Biology, I applied to the Humboldt CIRM Bridges program, and was lucky enough to be accepted. With a keen interest in the developing field of genome editing and the recent advent of the CRISPR-Cas9 system I chose to intern in the lab of a pioneer in the genome editing field, Dr. Matthew Porteus at Stanford, who focuses in genome editing hematopoietic stem cells to treat diseases such as sickle cell disease. In August of 2018 I began a PhD in Stanford’s Stem Cell and Regenerative Medicine program, where I am currently a second-year graduate student in the lab of Dr. Hiro Nakauchi, working on the development of human organs in interspecies human animal chimeras. The success that I’ve had and my acceptance into Stanford’s world class PhD program are a direct result of the opportunity that the CIRM Bridges internship provided me and the excellent training and instruction that I received from the Humboldt State Biology Program.”
ELISEBETH TORRETTI: “While looking for opportunities at HSU, I stumbled upon the CIRM Bridges program. It was perfect- a paid internship at high profile labs where I could expand my research skills for an entire year… the best fit (was) Jeanne Loring’s Lab at the Scripps Research Institute in La Jolla, CA. Dr. Loring is one of the premiere stem cell researchers in the world… (The lab’s) main focus is to develop a cure for Parkinson’s disease. (They) take skin cells known as fibroblasts and revert them into stem cells. These cells, called induced pluripotent stem cells (iPSCs) can then be differentiated into dopaminergic neurons and transplanted into the patient…. My project focused on a different disease: adenylate-cyclase 5 (ADCY5) — related dyskinesia. During my time at Dr. Loring’s lab I learned incredibly valuable research skills. I am now working in a mid-sized biotch company focusing on cancer research. I don’t think that would be possible in a competitive area like San Diego without my experience gained through the CIRM Bridges program.”
BRENDAN KELLY: “After completing my CIRM internship in Dr. Marius Wernig’s lab (in Stanford), I began working at a startup company called I Peace. I helped launch this company with Dr. Koji Tanabe, whom I met while working in my host lab. I am now at Cardiff University in Wales working on my PhD. My research involves using patient iPSC derived neurons to model Huntington’s disease. All this derived from my opportunity to partake in the CIRM-Bridges program, which opened doors for me.”
SAMANTHA SHELTON: “CIRM Bridges provided invaluable hands-on training in cell culture and stem cell techniques that have shaped my future in science. My CIRM internship in John Rubenstein’s Lab of Neural Development taught me amazing laboratory techniques such as stem cell transplantation as well as what goes into creating a harmonious and productive laboratory environment. My internship projects led to my first co-first author publication.
After my Bridges internship, I joined the Graduate Program for Neuroscience at Boston University. My PhD work aims to discover types of stem cells in the brain and how the structure of the brain develops early in life. During this time, I have focused on changes in brain development after Zika virus infection to better understand how microcephaly (small skulls and brains, often a symptom of Zika-DR) is caused. There is no doubt that CIRM not only made me a more competitive candidate for a doctoral degree but also provided me with tools to progress towards my ultimate goal of understanding and treating neurological diseases with stem cell technologies.”
DU CHENG: “Both my academic and business tracks started in the CIRM-funded…fellowship (at Stanford) where I invented the technology (the LabCam Microscope adapter) that I formed my company on (iDU Optics LLC). The instructor of the class, Dr. Amy Sprowles, encouraged me to carry on the idea. Later, I was able to get in the MD-PhD program at Weill Cornell Medical College because of the invaluable research experiences CIRM’s research program provided me. CIRM initiated the momentum to get me where I am today. Looking back, the CIRM Bridges Program is an instrumental jump-starter on my early career… I would not remotely be where I am without it.…”
CODY KIME: “Securing a CIRM grant helped me to take a position in the Nobel Prize winning Shinya Yamanaka Lab at the Gladstone Institutes, one of the most competitive labs in the new field of cell reprogramming. I then explored my own reprogramming interests, moving to the Kyoto University of Medicine, Doctor of Medical Sciences Program in Japan, and building a reprogramming team in the Masayo Takahashi Lab at RIKEN. My studies explore inducing cells to their highest total potential using less intrusive means and hacking the cell program. My systems are designed to inform my hypotheses toward a true お好みの細胞 (okonomi no cybo) technology, meaning ‘cells as you wish’ in Japanese, that could rapidly change any cell into another desired cell type or tissue.”
Sara Mills
SARA MILLS: “The CIRM Bridges program was the key early influencer which aided in my hiring of my first industry position at ViaCyte, Inc. Also a strongly CIRM funded institution, I was ultimately responsible for the process development of the VC-01™ fill, finish processes and cGMP documentation development. Most recently, with over two years at the boutique consulting firm of Dark Horse Consulting, Inc., I have been focusing on aseptic and cGMP manufacturing process development, risk analysis, CMC and regulatory filings, facility design and project management to advise growing cell and gene therapy companies, worldwide.”
Like warriors fighting to save lives, these young scientists are engaged in an effort to study and defeat chronic disease. It is to be hoped the California stem cell program will have its funding renewed, so the “Bridges” program can continue.
For more information on the Bridges program, which might help a young scientist (perhaps yourself) cut and paste the following URL:
One closing paragraph perhaps best sums up the Bridges experience:
“During my CIRM Bridges training in Stanford University, I was fortunate to work with Dr. Jill Helms, who so patiently mentored me on research design and execution. I ended up publishing 7 papers with her during the two-year CIRM internship and helped making significant progress of turning a Stem Cell factor into applicable therapeutic form, that is currently in preparation for clinical trial by a biotech company in Silicon Valley. I also learned from her how to write grants and publications, but more importantly, (to) never limit your potential by what you already know.” — Du Cheng
April 11th is World Parkinson’s Disease Awareness Day. To mark the occasion, we’re featuring the work of CIRM-funded researchers who are pursuing new, promising ideas to treat patients with this debilitating neurodegenerative disease.
Research: Birgitt and her team at the Parkinson’s Institute in Sunnyvale, California, are using CRISPR gene editing technology to reduce the levels of a toxic protein called alpha synuclein, which builds up in the dopaminergic brain cells affected by Parkinson’s disease.
Birgitt Schuele
“My hope is that I can contribute to stopping disease progression in Parkinson’s. If we can develop a drug that can get rid of accumulated protein in someone’s brain that should stop the cells from dying. If someone has early onset PD and a slight tremor and minor walking problems, stopping the disease and having a low dose of dopamine therapy to control symptoms is almost a cure.”
Parkinson’s disease in a dish. Dopaminergic neurons made from Parkinson’s patient induced pluripotent stem cells. (Image credit: Birgitt Schuele)
Research: Jeanne Loring and her team at the Scripps Research Institute in La Jolla, California, are deriving dopaminergic neurons from the iPSCs of Parkinson’s patients. Their goal is to develop a personalized, stem cell-based therapy for PD.
Jeanne Loring
“We are working toward a patient-specific neuron replacement therapy for Parkinson’s disease. By the time PD is diagnosed, people have lost more than half of their dopamine neurons in a specific part of the brain, and loss continues over time. No drug can stop the loss or restore the neurons’ function, so the best possible option for long term relief of symptoms is to replace the dopamine neurons that have died. We do this by making induced pluripotent stem cells from individual PD patients and turning them into the exact type of dopamine neuron that has been lost. By transplanting a patient’s own cells, we will not need to use potentially dangerous immunosuppressive drugs. We plan to begin treating patients in a year to two years, after we are granted FDA approval for the clinical therapy.”
Skin cells from a Parkinson’s patient (left) were reprogrammed into induced pluripotent stem cells (center) that were matured into dopaminergic neurons (right) to model Parkinson’s disease. (Image credit: Jeanne Loring)
Research: Justin Cooper-White and his team at Scaled Biolabs in San Francisco are developing a tool that will make clinical-grade dopaminergic neurons from the iPSCs of PD patients in a rapid and cost-effective manner.
Justin Cooper-White
“Treating Parkinson’s disease with iPSC-derived dopaminergic neuron transplantation has a strong scientific and clinical rationale. Even the best protocols are long and complex and generally have highly variable quality and yield of dopaminergic neurons. Scaled Biolabs has developed a technology platform based on high throughput microfluidics, automation, and deep data which can optimize and simplify the road from iPSC to dopaminergic neuron, making it more efficient and allowing a rapid transition to GMP-grade derivation of these cells. In our first 6 months of CIRM-funded work, we believe we have already accelerated and simplified the production of a key intermediate progenitor population, increasing the purity from the currently reported 40-60% to more than 90%. The ultimate goal of this work is to get dopaminergic neurons to the clinic in a robust and economical manner and accelerate treatment for Parkinson’s patients.”
High throughput differentiation of dopaminergic neuron progenitors in microbioreactor chambers in Scaled Biolabs’ cell optimization platform. Different chambers receive different differentiation factors, so that optimal treatments for conversion to dual-positive cells can be determined (blue: nuclei, red: FOXA2, green: LMX1A).
Research: Xinnan Wang and her team at Stanford University are studying the role of mitochondrial dysfunction in the brain cells affected in Parkinson’s disease.
Xinnan Wang
“Mitochondria are a cell’s power plants that provide almost all the energy a cell needs. When these cellular power plants are damaged by stressful factors present in aging neurons, they release toxins (reactive oxygen species) to the rest of the neuron that can cause neuronal cell death (neurodegeneration). We hypothesized that in Parkinson’s mutant neurons, mitochondrial quality control is impaired thereby leading to neurodegeneration. We aimed to test this hypothesis using neurons directly derived from Parkinson’s patients (induced pluripotent stem cell-derived neurons).”
Dopaminergic neurons derived from human iPSCs shown in green, yellow and red. (Image credit: Atossa Shaltouki, Stanford)
Oh well, it’s going to be another year of disappointment for me. Not only did I fail to get any Nobel Prize (I figured my blogs might give me a shot at Literature after they gave it to Bob Dylan last year), but I didn’t get a MacArthur Genius Award. Now I find out I haven’t even made the short list for the Stem Cell Person of the Year.
The Stem Cell Person of the Year award is given by UC Davis researcher, avid blogger and CIRM Grantee Paul Knoepfler. (You can vote for the Stem Cell Person of the Year here). In his blog, The Niche, Paul lists the qualities he looks for:
“The Stem Cell Person of the Year Award is an honor I give out to the person in any given year who in my view has had the most positive impact in outside-the-box ways in the stem cell and regenerative medicine field. I’m looking for creative risk-takers.”
“It’s not about who you know, but what you do to help science, medicine, and other people.”
Paul invites people to nominate worthy individuals – this year there are 20 nominees – people vote on which one of the nominees they think should win, and then Paul makes the final decision. Well, it is his blog and he is putting up the $2,000 prize money himself.
This year’s nominees are nothing if not diverse, including
Anthony Atala, a pioneering researcher at Wake Forest Institute for Regenerative Medicine in North Carolina
Bao-Ngoc Nguyen, who helped create California’s groundbreaking new law targeting clinics which offer unproven stem cell therapies
Judy Roberson, a tireless patient advocate, and supporter of stem cell research for Huntington’s disease
Stem cell transplants help put MS in remission: A combination of high dose immunosuppressive therapy and transplant of a person’s own blood stem cells seems to be a powerful tool in helping people with relapsing-remitting multiple sclerosis (RRMS) go into sustained remission.
Multiple sclerosis (MS) is an autoimmune disorder where the body’s own immune system attacks the brain and spinal cord, causing a wide variety of symptoms including overwhelming fatigue, blurred vision and mobility problems. RRMS is the most common form of MS, affecting up to 85 percent of people, and is characterized by attacks followed by periods of remission.
The HALT-MS trial, which was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), took the patient’s own blood stem cells, gave the individual chemotherapy to deplete their immune system, then returned the blood stem cells to the patient. The stem cells created a new blood supply and seemed to help repair the immune system.
Five years after the treatment, most of the patients were still in remission, despite not taking any medications for MS. Some people even recovered some mobility or other capabilities that they had lost due to the disease.
In a news release, Dr. Anthony Fauci, Director of NIAID, said anything that holds the disease at bay and helps people avoid taking medications is important:
“These extended findings suggest that one-time treatment with HDIT/HCT may be substantially more effective than long-term treatment with the best available medications for people with a certain type of MS. These encouraging results support the development of a large, randomized trial to directly compare HDIT/HCT to standard of care for this often-debilitating disease.”
Scripps Research Institute
Using stem cells to model brain development disorders. (Karen Ring) CIRM-funded scientists from the Scripps Research Institute are interested in understanding how the brain develops and what goes wrong to cause intellectual disabilities like Fragile X syndrome, a genetic disease that is a common cause of autism spectrum disorder.
Because studying developmental disorders in humans is very difficult, the Scripps team turned to stem cell models for answers. This week, in the journal Brain, they published a breakthrough in our understanding of the early stages of brain development. They took induced pluripotent stem cells (iPSCs), made from cells from Fragile X syndrome patients, and turned these cells into brain cells called neurons in a cell culture dish.
They noticed an obvious difference between Fragile X patient iPSCs and healthy iPSCs: the patient stem cells took longer to develop into neurons, a result that suggests a similar delay in fetal brain development. The neurons from Fragile X patients also had difficulty forming synaptic connections, which are bridges that allow for information to pass from one neuron to another.
Scripps Research professor Jeanne Loring said that their findings could help to identify new drug therapies to treat Fragile X syndrome. She explained in a press release;
“We’re the first to see that these changes happen very early in brain development. This may be the only way we’ll be able to identify possible drug treatments to minimize the effects of the disorder.”
Looking ahead, Loring and her team will apply their stem cell model to other developmental diseases. She said, “Now we have the tools to ask the questions to advance people’s health.”
A Day to Discover What Stem Cells Are All about. (Karen Ring) Everyone is familiar with the word stem cells, but do they really know what these cells are and what they are capable of? Scientists are finding creative ways to educate the public and students about the power of stem cells and stem cell research. A great example is the University of Southern California (USC), which is hosting a Stem Cell Day of Discovery to educate middle and high school students and their families about stem cell research.
The event is this Saturday at the USC Health Sciences Campus and will feature science talks, lab tours, hands-on experiments, stem cell lab video games, and a resource fair. It’s a wonderful opportunity for families to engage in science and also to expose young students to science in a fun and engaging way.
Interest in Stem Cell Day has been so high that the event has already sold out. But don’t worry, there will be another stem cell day next year. And for those of you who don’t live in Southern California, mark your calendars for the 2017 Stem Cell Awareness Day on Wednesday, October 11th. There will be stem cell education events all over California and in other parts of the country during that week in honor of this important day.
It’s the year 2286. The transmission signal of an alien space probe is wreaking havoc on Earth, knocking out the worldwide power grid and causing massive storms. It turns out the mysterious orbiting probe is trying to communicate with humpback whales through whale song and the devastation won’t stop until contact is made. But there’s a tiny problem: in that future, the humpback has long since become extinct. So the captain and crew travel back in time to snag two whales and save 23rd century civilization. Phew!
My fellow science fiction nerds will recognize that plot line from 1986’s Star Trek IV: A Voyage Home. It’s pure fantasy and yet there is a real lesson for our present day world: you shouldn’t underestimate how the extinction of a species will impact our world. For instance, the collapse and potential extinction of the bee population and other pollinators threatens to destabilize our global food supply.
Northern White Rhinos: At the Brink of Extinction Beyond how it may affect us humans, I think there’s also a moral obligation to save endangered species that have dwindled in number directly due to human actions. It may be too late for the northern white rhino though. Because their horns are highly sought after as a status symbol and for use in traditional medicine, poachers have wiped out the population and now only three – Sudan, Najin and Fatu (grandfather, mother and daughter) – exist in the world. Sadly, none of them can breed naturally so they quietly graze in a Kenyan conservation park as their species heads towards extinction.
One of the three remaining northern white rhinos in the world (Image source: The Guardian)
Jeanne Loring, a CIRM grantee and professor at The Scripps Research Institute, still sees a glimmer of hope in the form of stem cells. In an essay published yesterday in Genetic Engineering and Biotechnology News, Loring describes her research team’s efforts to apply stem cell technology toward saving the Northern White Rhino and other endangered species.
Their efforts began about ten years ago in 2007, the same year that Shinya Yamanaka’s lab first reported that human fibroblasts, collected from a skin sample, can be reprogrammed into an embryonic stem cell-like state with the capacity to indefinitely make copies of themselves and to specialize into almost every cell type of the body. The properties of these induced pluripotent stem (iPS) cells have provided an important means for studying all sorts of human diseases in a lab dish and for deriving potential cell therapies.
FrozenZoo® and iPS Cells: A Modern Day Noah’s Ark?
But it was a free tour at the San Diego Safari Park just two months after Yamanka’s discovery which inspired the Loring lab to chart this additional research path using iPS cells. In exchange for the free safari ride, the team reciprocated by chatting with Oliver Ryder, director of the San Diego Zoo Institute for Conservation Research, about using stem cells to help save endangered species. Ryder’s institute runs the FrozenZoo® a cell and tissue bank containing thousands of frozen samples from a diverse set of species. In her essay, Loring recounts what happened after the visit:
“It was obvious to us: why not try to reprogram fibroblasts from the FrozenZoo®? When my group returned to the lab from the safari, I asked them: who would like to try to reprogram fibroblasts from an endangered species? It was far from a safe bet, but a young postdoctoral researcher who had recently joined my lab from Israel said that she’d love to give it a try. Inbar Friedrich Ben-Nun spent the next couple of years trying out methods in parallel on human cells and fibroblasts from the zoo. We chose fibroblasts from the drill because it is [an endangered] primate, making it more likely that the technology used for humans would work.
Oliver [Ryder] chose the northern white rhino, a particular favorite of his, and one of the world’s most endangered mammals. Through hard work and insight, Inbar reprogrammed both species, and in 2011, we published the first report of making iPSCs from endangered species (Ben-Nun, et al., 2011). Nature Methods featured our work, with a cover illustration of an ark stuffed with endangered animals.”
So how exactly would these iPS cells be used to save the northern white rhino and other animals from the brink of extinction? Last December, Ben-Nun along with 20 other scientists and zoologists from four continents met in Vienna to map out a strategy. They published their plan on May 3rd in Zoo Biology.
The Stem Cell-Based Plan to Save the Northern White In the first phase, an in vitro fertilization (IVF) procedure for the rhino – never before attempted – will be worked out. Frozen sperm samples from four now-deceased rhinos plus one sample from Sudan are ready for IVF. Researchers then hope to collect eggs from Najin and Fatu and implant embryos in surrogates of a related species, the southern white rhino. However, even if IVF is successful, the offspring would not represent enough genetic diversity to ultimately thrive as a species in the wild. So in the second phase, iPS cells will be generated using tissue fibroblast samples from several more northern whites that were banked in The FrozenZoo®. Those iPS cells will be specialized into sperm and eggs to provide a larger, more diverse set of embryos which again will be implanted in surrogate rhinos. Breeding animals using iPS-derived sperm and eggs has only been successful in mice so much work remains.
“Does this plan have any chance of succeeding?” Loring asks. Her response is cautiously optimistic:
“I know it will be difficult, but I think it’s not impossible. Perhaps the most important advance is that such a diverse group agreed on a plan—it wasn’t just a stem cell biologist like me imagining how the cells might be used, but rather a whole chain of experts who can imagine how to accomplish each step.”
Not all experts agree with this strategy. In a Nature News interview back in May, Michael Knight, chair of the International Union for Conservation Nature’s African Rhino Specialist Group, expressed concerns that the effort is misdirected:
“It’s Star Trek-type science. They should not be pushing this idea that they’re saving a species. If you want to save a [rhino] species, put your money into southern white conservation.”
IMHO Knight’s point is well-taken that conventional conservation approaches are critical to ensure that the southern white rhino doesn’t meet the same disastrous fate as the northern white. But if the funding is available, it seems worth the effort to also attempt this innovative iPS strategy, a technology that’s deep in development now and not awaiting Captain Kirk’s distant Star Trek future.
Imagine how frustrating it would be to not know whether you could physically sit through a dinner with friends or to worry about getting stuck in the grocery isle, fighting against a body that refuses to move. These nightmare-like experiences are what many Parkinson’s disease (PD) patients deal with on a daily basis.
PD affects approximately one million people in the US, and there is no prevention or cure. While substantial funding efforts are being dedicated to PD research (CIRM, Michael J. Fox Foundation, Parkinson’s Disease Foundation, to name a few), a cure is still years or maybe even decades away.
However, a new stem cell therapy from Australia has the potential to make waves in what’s been a relatively flat sea of PD stem cell therapies that haven’t yet secured the funding or jumped the regulatory hurdles to make it into clinical trials. Biotech journalist Bradley Fikes broke the story yesterday in the San Diego Union Tribune. Fikes is one of my favorite science writers so instead of attempting to re-write an already eloquent piece, I’ll just mention a few highlights.
Stem cells down under
International Stem Cell Corporation (ISCO), a company based in Carlsbad, California, has developed a stem cell therapy that involves transplanting brain stem cells into the brains of PD patients. While stem cell therapy is viewed by some as the holy grail for PD – having the potential to replace lost dopamine-producing nerve cells in the brain – so far, no stem cell-derived therapy has been approved for testing in PD patients. (Previous clinical trials using fetal stem cells didn’t pan out.)
The Australian government approved the use of ISCO’s parthenogenic stem cell therapy in twelve PD patients in a clinical trial that is slated to start in the first quarter of 2016 (pending final approval from the Royal Melbourne Hospital review board). This therapy uses brain stem cells derived from pluripotent stem cells obtained from unfertilized human eggs, thus avoiding the ethical issues attached to use of embryonic stem cells. (For sciency details check out the ISCO website).
The goal of the trial will be to determine if ISCO’s stem cell therapy is safe and also effective at reducing PD symptoms like tremors and stunted movement. Fikes explained that ISCO chose Australia for it’s proposed clinical trial for regulatory reasons.
“The nation’s clinical trial system is more ‘interactive’, which allows for better collaboration with Australia’s Therapeutic Goods Administration on trial design.”
A comparison of primate brains to show an increase in the number of neurons after treatment with ISCO’s stem cells. The left side is a control sample. The right side is from a treated brain. — International Stem Cell Corp.
Great minds think alike
ISCO’s is only one of a handful of groups proposing stem cell therapies for PD. Fikes mentioned other therapies currently being tested that are derived from embryonic stem cells, induced pluripotent stem cells (iPSCs), and adult stem cells like the mesenchymal and fat stem cells.
Jeanne Loring, Scripps Research Institute
He also highlighted important ongoing research by CIRM grantee Dr. Jeanne Loring from the Scripps Research Institute. Loring founded the Summit for Stem Cell organization that’s generating iPSCs from PD patients with hopes of treating these patients with a dose of their own brain stem cells.
When asked about the ISCO study, she told Fikes that she sees ISCO as a “partner in fighting Parkinson’s.”
“The whole idea is to treat patients by whatever means possible.” – Loring
L to R: Don Gibbons, CIRM; Jeanne Loring; Beth Roxland; Aaron Levine
In the last few years some 24 states have approved so-called “Right to Try” laws. These are intended to give terminally ill patients faster and easier access to experimental therapies. But a panel of experts at the World Stem Cell Summit in Atlanta today said they are more symbolic than anything and do little to actually help patients get much-needed therapies.
The Right to Try laws are modeled after a federal law that allows “compassionate use” of experimental medications and lets doctors prescribe investigational medicines being safely used in early stage clinical trials.
Beth Roxland, a bioethicist with Johnson & Johnson, says the name of the law is misleading:
“If you look at the actual text of these laws they only say you have the right to “ask” for these drugs. That right already exists in federal law but neither federal law nor these Right to Try laws say you have the right to access.”
Aaron Levine from Georgia Tech says it’s also misleading to assume that just because a state passes a Right to Try law that it has any legal impact. He says state laws don’t over rule the Food and Drug Administration’s (FDA) regulation of this area and so the federal government would still have the authority to stop this kind of access.
But Levine says these laws are interesting in that they are indicative of the growing determination of patients and patient advocates to work around obstacles to access and have a bigger say in their own care.
One of the audience members, William Decker from Baylor College of Medicine, says that in Texas a law was recently crafted saying that as long as a potential therapy had gone through a Phase 1 safety trial it should be offered to the public and the public should be able to pay for it.
“If you know how clinical trials work you know you can get almost any schlock through a Phase 1 trial and the kinds of things that you can get to the public without any idea if they work often turn out to not be very useful. We saw this as an avenue to promote fraud, and the last thing you should be doing to a dying patient is take their money or divert their attention away from something that might help them.”
Decker and his colleagues argued before the Texas Legislature that potential therapies should at least have to go through a Phase 2 trial to make sure they were not only safe but also showed some benefit for patients. In the end Texas lawmakers rejected the Phase 2 idea but did say patients could not be charged for the therapy, and there could be no compensation from insurers or anyone else for the manufacturer of the therapy.
He says removing the financial benefits and incentives pretty much ensured that no company would offer patients a therapy under this law.
Jeanne Loring, a CIRM grantee from the Scripps Research Institute, says that likely won’t stop other clinics in other states:
“Some stem cell clinics are using adipose (stem cells derived from fat) therapy as an option for every disease imaginable and I’m sure some will take advantage of these laws to say it gives them the right to offer these to patients and the patients will pay for them directly. “
Roxland says that may already be happening:
“I think there is some evidence on the stem cell side that companies have popped up in states that have these laws, to make it easier to offer their therapies to patients.”
The panel agreed that in most cases these laws don’t give patients any rights they don’t already have, but do give the appearance of making access easier. They said it’s feel-good legislation, allowing people to feel they are doing something without actually doing anything.
Aaron Levine said that while some companies may try to take advantage of these laws, the most serious ones won’t:
“Almost any legitimate company that wants an FDA approved product wouldn’t want to take advantage of these laws. It could put their product at risk. Most companies that need to work with the FDA have no incentive to go this route.”
![IMG_0771[4]](https://aholdencirm.files.wordpress.com/2015/12/img_07714.jpg)
The Stem Cellar 