Study shows connection between bipolar disorder and neuroinflammation

Astrocytes, which provide structural support and protection for neurons and also supply them with nutrients and oxygen.

Bipolar disorder (BPD) is a mental disorder that causes unusual shifts in mood, energy, activity levels, concentration, and the ability to carry out day-to-day tasks. In the United States, recent research has shown that 1.6% of the population has BPD, which is roughly over 4 million people. Those with BPD are more likely to have conditions associated with chronic inflammation such as hypertension and diabetes. It is because of this that scientists have been studying the connection between inflammation and BPD for quite some time.

In a new study, researchers at the Salk Institute for Biological Studies, UC San Diego, and the Institute of Psychiatry and Neuroscience of Paris have found evidence that astrocytes, a certain type of brain cell, can trigger inflammation more easily in those that have BPD. What’s more, these astrocytes can be linked to decreased brain activity that could be harmful to mental health.

Astrocytes are star shaped (as the word “astro” might suggest) and help support neurons, the cells that relay information around the brain. One of these supporting roles includes helping trigger inflammation in the brain and the surrounding nervous system to help with injury or infection. The researchers believe that this process can go wrong in people with BPD and that astrocytes can play a role in this dysfunctional inflammation.

For this study, the team used induced pluripotent stem cells (iPSCs), a kind of stem cell that can turn into virtually any type of cell, that they created from patients with BPD and patients without BPD. They converted these iPSCs into astrocytes and compared those that came from BPD patients to those that did not. What they found is that the astrocytes from patients with BPD were noticeably different. The BPD astrocytes had a higher expression of a protein that triggers an inflammatory response when compared to the non-BPD astrocytes. When they exposed neurons to the BPD astrocytes, the team saw decreased levels of neural activity compared to the non-BPD astrocytes. Lastly, when the researchers blocked the inflammatory protein, the neurons were less affected by the BPD astrocytes.

“Our study suggests that normal function of astrocytes is affected in bipolar disorder patients’ brains, contributing to neuroinflammation,” said Dr. Renata Santos, a researcher at the Salk Institute as well as the Institute of Psychiatry and Neuroscience of Paris, in a news release.

The team hopes that their findings can not only provide insight into BPD, but to other mental illnesses linked to inflammation such as schizophrenia. The ultimate goal is to help advance research into astrocytes and inflammation in order to develop treatments that might reverse the harmful bodily changes seen in those with BPD and other mental disorders.

The full study was published in Stem Cell Reports.

A word from our Chair, several in fact

In 2005, the New Oxford American Dictionary named “podcast” its word of the year. At the time a podcast was something many had heard of but not that many actually tuned in to. My how times have changed. Now there are some two million podcasts to chose from, at least according to the New York Times, and who am I to question them.

Yesterday, in the same New York Times, TV writer Margaret Lyons, wrote about how the pandemic helped turn her from TV to podcasts: “Much in the way I grew to prefer an old-fashioned phone call to a video chat, podcasts, not television, became my go-to medium in quarantine. With their shorter lead times and intimate production values, they felt more immediate and more relevant than ever before.”

I mention this because an old colleague of ours at CIRM, Neil Littman, has just launched his own podcast and the first guest on it was Jonathan Thomas, Chair of the CIRM Board. Their conversation ranged from CIRM’s past to the future of the regenerative field as a whole, with a few interesting diversions along the way. It’s fun listening. And as Margaret Lyons said it might be more immediate and more relevant than ever before.

Charting a course for the future

A new home for stem cell research?

Have you ever been at a party where someone says “hey, I’ve got a good idea” and then before you know it everyone in the room is adding to it with ideas and suggestions of their own and suddenly you find yourself with 27 pages of notes, all of them really great ideas. No, me neither. At least, not until yesterday when we held the first meeting of our Scientific Strategy Advisory Panel.

This is a group that was set up as part of Proposition 14, the ballot initiative that refunded CIRM last November (thanks again everyone who voted for that). The idea was to create a panel of world class scientists and regulatory experts to help guide and advise our Board on how to advance our mission. It’s a pretty impressive group too. You can see who is on the SSAP here.  

The meeting involved some CIRM grantees talking a little about their work but mostly highlighting problems or obstacles they considered key issues for the future of the field as a whole. And that’s where the ideas and suggestions really started flowing hard and fast.

It started out innocently enough with Dr. Amander Clark of UCLA talking about some of the needs for Discovery or basic research. She advocated for a consortium approach (this quickly became a theme for many other experts) with researchers collaborating and sharing data and findings to help move the field along.

She also called for greater diversity in research, including collecting diverse cell samples at the basic research level, so that if a program advanced to later stages the findings would be relevant to a wide cross section of society rather than just a narrow group.

Dr. Clark also said that as well as supporting research into neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, there needed to be a greater emphasis on neurological conditions such as autism, bipolar disorder and other mental health problems.

(CIRM is already committed to both increasing diversity at all levels of research and expanding mental health research so this was welcome confirmation we are on the right track).

Dr. Mike McCun called for CIRM to take a leadership role in funding fetal tissue research, things the federal government can’t or won’t support, saying this could really help in developing an understanding of prenatal diseases.

Dr. Christine Mummery, President of ISSCR, advocated for support for early embryo research to deepen our understanding of early human development and also help with issues of infertility.

Then the ideas started coming really fast:

  • There’s a need for knowledge networks to share information in real-time not months later after results are published.
  • We need standardization across the field to make it easier to compare study results.
  • We need automation to reduce inconsistency in things like feeding and growing cells, manufacturing cells etc.
  • Equitable access to CRISPR gene-editing treatments, particularly for underserved communities and for rare diseases where big pharmaceutical companies are less likely to invest the money needed to develop a treatment.
  • Do a better job of developing combination therapies – involving stem cells and more traditional medications.

One idea that seemed to generate a lot of enthusiasm – perhaps as much due to the name that Patrik Brundin of the Van Andel Institute gave it – was the creation of a CIRM Hotel California, a place where researchers could go to learn new techniques, to share ideas, to collaborate and maybe take a nice cold drink by the pool (OK, I just made that last bit up to see if you were paying attention).

The meeting was remarkable not just for the flood of ideas, but also for its sense of collegiality.  Peter Marks, the director of the Food and Drug Administration’s Center for Biologics Evaluation and Research (FDA-CBER) captured that sense perfectly when he said the point of everyone working together, collaborating, sharing information and data, is to get these projects over the finish line. The more we work together, the more we will succeed.

Scientists use stem cells to create Neanderthal-like “mini-brain”

Alysson R. Muotri, Ph.D.

The evolution of modern day humans has always been a topic that has been shrouded in mystery. Some of what is known is that Neanderthals, an archaic human species that lived on this planet up until about 11,700 years ago, interbred with our species (Homo sapiens) at some point in time. Although their brains were about as big as ours, anthropologists think they must have worked differently due to the fact that they never achieved the sophisticated technology and artistry modern humans have.

Since brains do not fossilize, it has been challenging to see how these two early human species have changed over time. To help answer this question, Dr. Alysson Muotri and his team at UC San Diego created so-called “mini-brains” using stem cells and gene editing technology to better understand how the Neanderthal brain might have functioned.

For this study, Dr. Muotri and his team closely evaluated the differences in genes between modern day humans and Neanderthals. They found a total of 61 different genes, but for this study focused on one in particular that plays a role in influencing early brain development.

Brain organoids that carry a Neanderthal gene.
Image courtesy of the Muotri Lab and UCSD

Using gene editing technology, the team introduced the Neanderthal version of the gene into human stem cells. These stem cells, which have the ability to become various cell types, were then used to create brain cells. These cells eventually formed brain organoids or “mini-brains”, 3D models made of cells that can be used to analyze certain features of the human brain. Although they are far from perfect replicas, they can be used to study physical structure and other characteristics. In a previous CIRM funded study, Dr. Muotri had used “mini-brains” to model an autism spectrum disorder and help test treatments.

Dr. Muotri and his team found that the Neanderthal-like brain organoids looked very different than modern human brain organoids, having a distinctly different shape. Upon further analysis, the team found that modern and Neanderthal-like brain organoids also differed in the way their cells grow. Additionally, the way in which connections between neurons formed as well as the proteins involved in forming these connections differed between the two organoids. Finally, electrical impulses displayed higher activity at earlier stages, but didn’t synchronize in networks in Neanderthal-like brain organoids.

According to Muotri, the neural network changes in Neanderthal-like brain organoids mimic the way newborn primates acquire new abilities more rapidly than human newborns.

In a news release from UCSD, Dr. Muotri discusses the next steps in advancing this research.

“This study focused on only one gene that differed between modern humans and our extinct relatives. Next we want to take a look at the other 60 genes, and what happens when each, or a combination of two or more, are altered. We’re looking forward to this new combination of stem cell biology, neuroscience and paleogenomics.”

The full results of this study were published in Science.

CIRM funded researchers discover link between Alzheimer’s gene and COVID-19

Dr. Yanhong Shi (left) and Dr. Vaithilingaraja Arumugaswami (right)

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. Today we focus on groundbreaking CIRM funded research related to COVID-19 that was recently published.

It’s been almost a year since the world started hearing about SARS-CoV-2, the virus that causes COVID-19.  In our minds, the pandemic has felt like an eternity, but scientists are still discovering new things about how the virus works and if genetics might play a role in the severity of the virus.  One population study found that people who have ApoE4, a gene type that has been found to increase the risk of developing Alzheimer’s, had higher rates of severe COVID-19 and hospitalizations.

It is this interesting observation that led to important findings of a study funded by two CIRM awards ($7.4M grant and $250K grant) and conducted by Dr. Yanhong Shi at City of Hope and co-led by Dr. Vaithilingaraja Arumugaswami, a member of the UCLA Broad Stem Cell Research Center.  The team found that the same gene that increases the risk for Alzheimer’s disease can increase the susceptibility and severity of COVID-19.

At the beginning of the study, the team was interested in the connection between SARS-CoV-2 and its effect on the brain.  Due to the fact that patients typically lose their sense of taste and smell, the team theorized that there was an underlying neurological effect of the virus.  

The team first created neurons and astrocytes.  Neurons are cells that function as the basic working unit of the brain and astrocytes provide support to them.  The neurons and astrocytes were generated from induced pluripotent stem cells (iPSCs), which are a kind of stem cell that can become virtually any type of cell and can be created by “reprogramming” the skin cells of patients.  The newly created neurons and astrocytes were then infected with SARS-CoV-2 and it was found that they were susceptible to infection.

Next, the team used iPSCs to create brain organoids, which are 3D models that mimic certain features of the human brain.  They were able to create two different organoid models: one that contained astrocytes and one without them.  They infected both brain organoid types with the virus and discovered that those with astrocytes boosted SARS-CoV-2 infection in the brain model. 

The team then decided to further study the effects of ApoE4 on susceptibility to SARS-CoV-2.  They did this by generating neurons from iPSCs “reprogrammed” from the cells of an Alzheimer’s patient.  Because the iPSCs were derived from an Alzheimer’s patient, they contained ApoE4.  Using gene editing, the team modified some of the ApoE4 iPSCs created so that they contained ApoE3, which is a gene type considered neutral.  The ApoE3 and ApoE4 iPSCs were then used to generate neurons and astrocytes.

The results were astounding.  The ApoE4 neurons and astrocytes both showed a higher susceptibility to SARS-CoV-2 infection in comparison to the ApoE3 neurons and astrocytes.  Moreover, while the virus caused damage to both ApoE3 and ApoE4 neurons, it appeared to have a slightly more severe effect on ApoE4 neurons and a much more severe effect on ApoE4 astrocytes compared to ApoE3 neurons and astrocytes. 

“Our study provides a causal link between the Alzheimer’s disease risk factor ApoE4 and COVID-19 and explains why some (e.g. ApoE4 carriers) but not all COVID-19 patients exhibit neurological manifestations” says Dr. Shi. “Understanding how risk factors for neurodegenerative diseases impact COVID-19 susceptibility and severity will help us to better cope with COVID-19 and its potential long-term effects in different patient populations.”

In the last part of the study, the researchers tested to see if the antiviral drug remdesivir inhibits virus infection in neurons and astrocytes.  They discovered that the drug was able to successfully reduce the viral level in astrocytes and prevent cell death.  For neurons, it was able to rescue them from steadily losing their function and even dying. 

The team says that the next steps to build on their findings is to continue studying the effects of the virus and better understand the role of ApoE4 in the brains of people who have COVID-19.  Many people that developed COVID-19 have recovered, but long-term neurological effects such as severe headaches are still being seen months after. 

“COVID-19 is a complex disease, and we are beginning to understand the risk factors involved in the manifestation of the severe form of the disease” says Dr. Arumugaswami.  “Our cell-based study provides possible explanation to why individuals with Alzheimer’s’ disease are at increased risk of developing COVID-19.”

The full results to this study were published in Cell Stem Cell.

Stem cell research reveals path to schizophrenia

3d illustration of brain nerve cells – Photo courtesy Science Photo

If you don’t know what’s causing a problem it’s hard to come up with a good way to fix it. Mental health is the perfect example. With a physical illness you can see what the problem is, through blood tests or x-rays, and develop a plan to tackle it. But with the brain, that’s a lot harder. You can’t autopsy a brain while someone is alive, they tend to object, so you often only see the results of a neurological illness when they’re dead.

And, says Consuelo Walss-Bass, PhD, a researcher at the University of Texas Health Science Center at Houston (UTHealth), with mental illness it’s even more complicated.

“Mental health research has lagged behind because we don’t know what is happening biologically. We are diagnosing people based on what they are telling us. Even postmortem, the brain tissue in mental health disorders looks perfectly fine. In Alzheimer’s disease, you can see a difference compared to controls. But not in psychiatric disorders.”

So Wals-Bass and her team came up with a way to see what was going on inside the brain of someone with schizophrenia, in real time, to try and understand what puts someone at increased risk of the disorder.

In the study, published in the journal Neuropsychopharmacology, the researchers took blood samples from a family with a high incidence of schizophrenia. Then, using the iPSC method, they turned those cells into brain neurons and compared them to the neurons of individuals with no family history of schizophrenia. In effect, they did a virtual brain biopsy.

By doing this they were able to identify five genes that had previously been linked to a potential higher risk of schizophrenia and then narrow that down further, highlighting one gene called SGK1 which blocked an important signalling pathway in the brain.

In a news release, Walss-Bass says this findings could have important implications in treating patients.

“There is a new antipsychotic that just received approval from the Food and Drug Administration that directly targets the pathway we identified as dysregulated in neurons from the patients, and several other antipsychotics also target this pathway. This could help pinpoint who may respond better to treatments.”

Finding the right treatment for individual patients is essential in helping them keep their condition under control. A study in the medical journal Lancet estimated that six months after first being prescribed common antipsychotic medication, as many as 50% of patients are either taking the drugs haphazardly or not at all. That’s because they often come with unpleasant side effects such as weight gain, drowsiness and a kind of restless anxiety.

By identifying people who have specific gene pathways linked to schizophrenia could help us better tailor medications to those who will benefit most by them.

“Mini-brains” model an autism spectrum disorder and help test treatments

Alysson Muotri, PhD, professor and director of the Stem Cell Program at UC San Diego School of Medicine
and member of the Sanford Consortium for Regenerative Medicine.
Image credit: UC San Diego Health

Rett syndrome is a rare form of autism spectrum disorder that impairs brain development and causes problems with movement, speech, and even breathing. It is caused by mutations in a gene called MECP2 and primarily affects females. Although there are therapies to alleviate symptoms, there is currently no cure for this genetic disorder.

With CIRM funding ($1.37M and $1.65M awards), Alysson Muotri, PhD and a team of researchers at the University of California San Diego School of Medicine and Sanford Consortium for Regenerative Medicine have used brain organoids that mimic Rett syndrome to identify two drug candidates that returned the “mini-brains” to near-normal. The drugs restored calcium levels, neurotransmitter production, and electrical impulse activity.

Brain organoids, also referred to as “mini-brains”, are 3D models made of cells that can be used to analyze certain features of the human brain. Although they are far from perfect replicas, they can be used to study changes in physical structure or gene expression over time.

Dr. Muotri and his team created induced pluripotent stem cells (iPSCs), a type of stem cell that can become virtually any type of cell. For the purposes of this study, they were created from the skin cells of Rett syndrome patients. The newly created iPSCs were then turned into brain cells and used to create “mini-brains”, thereby preserving each Rett syndrome patient’s genetic background. In addition to this, the team also created “mini-brains” that artificially lack the MECP2 gene, mimicking the issues with the same gene observed in Rett syndrome.

Lack of the MECP2 gene changed many things about the “mini-brains” such as shape, neuron subtypes present, gene expression patterns, neurotransmitter production, and decreases in calcium activity and electrical impulses. These changes led to major defects in the emergence of brainwaves.

To correct the changes caused by the lack of the MECP2 gene, the team treated the brain organoids with 14 different drug candidates known to affect various brain cell functions. Of all the drugs tested, two stood out: nefiracetam and PHA 543613. The two drugs resolved nearly all molecular and cellular symptoms observed in the Rett syndrome “mini-brains”, with the number active neurons doubling post treatment.

The two drugs were previously tested in clinical trials for the treatment of other conditions, meaning they have been shown to be safe for human consumption.

In a news release from UC San Diego Health, Dr. Muotri stresses that although the results for the two drugs are promising, the end treatment for Rett syndrome may require a multi-drug cocktail of sorts.

“There’s a tendency in the neuroscience field to look for highly specific drugs that hit exact targets, and to use a single drug for a complex disease. But we don’t do that for many other complex disorders, where multi-pronged treatments are used. Likewise, here no one target fixed all the problems. We need to start thinking in terms of drug cocktails, as have been successful in treating HIV and cancers.”

The full results of this study were published in EMBO Molecular Medicine.

Persistence pays off in search for clue to heart defects

A team of scientists led by Benoit Bruneau (left), including Irfan Kathiriya (center) and Kavitha Rao (right), make inroads into understanding what genes are improperly deployed in some cases of congenital heart disease.  Photo courtesy Gladstone Institute

For more than 20 years Dr. Benoit Bruneau has been trying to identify the causes of congenital heart disease, the most common form of birth defect in the U.S. It turns out that it’s not one cause, but many.

Congenital heart disease covers a broad range of defects, some relatively minor and others life-threatening and even fatal. It’s been known that a mutation in a gene called TBX5 is responsible for some of these defects, so, in a CIRM-funded study ($1.56 million), Bruneau zeroed in on this mutation to see if it could help provide some answers.

In the past Bruneau, the director of the Gladstone Institute of Cardiovascular Disease, had worked with a mouse model of TBX5, but this time he used human induced pluripotent stem cells (iPSCs). These are cells that can be manipulated in the lab to become any kind of cell in the human body. In a news release Bruneau says this was an important step forward.

“This is really the first time we’ve been able to study this genetic mutation in a human context. The mouse heart is a good proxy for the human heart, but it’s not exactly the same, so it’s important to be able to carry out these experiments in human cells.”

The team took some iPSCs, changed them into heart cells, and used a gene editing tool called CRISPR-Cas9 to create the kinds of mutations in TBX5 that are seen in people with congenital heart disease. What they found was some genes were affected a lot, some not so much. Which is what you might expect in a condition that causes so many different forms of problems.

“It makes sense that some are more affected than others, but this is the first experimental data in human cells to show that diversity,” says Bruneau.

But they didn’t stop there. Oh no. Then they did a deep dive analysis to understand how the different ways that different cells were impacted related to each other. They found some cells were directly affected by the TBX5 mutation but others were indirectly affected.

The study doesn’t point to a simple way of treating congenital heart disease but Bruneau says it does give us a much better understanding of what’s going wrong, and perhaps will give us better ideas on how to stop that.

“Our new data reveal that the genes are really all part of one network—complex but singular—which needs to stay balanced during heart development. That means if we can figure out a balancing factor that keeps this network functioning, we might be able to help prevent congenital heart defects.”

The study is published in the journal Developmental Cell.

CIRM-funded study discovers potential therapy for one of the leading causes of heart disease

Dr. Deepak Srivastava and his team found a drug candidate that could help prevent tens of thousands of heart surgeries every year. Image Credit: Gladstones Institute

According to the Center for Disease Control and Prevention (CDC), heart disease is the leading cause of death for men, women, and people of most racial and ethnic groups in the United States. About 655,000 Americans die from heart disease each year, which is about one in every four deaths.

Calcific aortic valve disease, the third leading cause of heart disease overall, occurs when calcium starts to accumulate in the heart valves and vessels over time, causing them to gradually harden like bone. This leads to obstruction of blood flow out of the heart’s pumping chamber, causing heart failure. Unfortunately there is no treatment for this condition, leaving patients only with the option of surgery to replace the heart valve once the hardening is severe enough.

But thanks to a CIRM-funded ($2.4 million) study conducted by Dr. Deepak Srivastava and his team at the Gladstone Institutes, a potential drug candidate for heart valve disease was discovered. It has been found to function in both human cells and animals and is ready to move toward a clinical trial.

For this study, Dr. Srivastava and his team looked for drug-like molecules that had the potential to correct the mechanism in heart valve disease that leads to gradual hardening. To do so, the team first had to determine the network of genes that are turned on or off in the diseased cells.

Once the genes were identified, they used an artificial intelligence method to train a machine learning program to detect whether a cell was healthy or diseased based on the network of genes identified. They proceeded to treat the diseased human cells with nearly 1,600 molecules in order to identify any drugs that would cause the machine learning program to reclassify diseased cells as healthy. The team successfully identified a few molecules that could correct diseased cells back to a healthy state.

Dr. Srivastara then collaborated with Dr. Anna Malashicheva, from the Russian Academy of Sciences, who had collected valve cells from over 20 patients at the time of surgical replacement. Using the valve cells that Dr. Malashicheva had collected, Dr. Srivastara and his team conducted a “clinical trial in a dish” in which they tested the molecules they had previously identified in the cells from the 20 patients with aortic valve hardening. The results were remarkable, as the molecule that seemed most effective in the initial study was able to restore these patients’ cells as well.

The final step taken was to determine whether the drug-like molecule would actually work in a whole, living organ. To do this, Dr. Srivastava and his team did a “pre-clinical trial” in a mouse model of the disease. The team found that the therapeutic candidate could successfully prevent and treat aortic valve disease. In young mice who had not yet developed the disease, the therapy prevented the hardening of the valve. In mice that already had the disease, the therapy was able to halt the disease and, in some cases, reverse it. This finding is especially important since most patients aren’t diagnosed until hardening of the heart valve has already begun.

Dr. Deepak Srivastava (left) and Dr. Christina V. Theodoris (right)
Image Credit: Gladstones Institute

Dr. Christina V. Theodoris, a lead author of the study who is now completing her residency in pediatric genetics, was a graduate student in Dr. Srivastava’s lab and played a critical role in this research. Her first project was to convert the cells from patient families into induced pluripotent stem cells (iPSCs), which have the potential of becoming any cell in the body. The newly created iPSCs were then turned into cells that line the valve, allowing the team to understand why the disease occurs. Her second project was to make a mouse model of calcific aortic valve disease, which enabled them to start using the models to identify a therapy.

In a press release from Gladstone Institutes, Dr. Theodoris, discusses the impact of the team’s research.

“Our strategy to identify gene network–correcting therapies that treat the core disease mechanism may represent a compelling path for drug discovery in a range of other human diseases. Many therapeutics found in the lab don’t translate well to humans or focus only on a specific symptom. We hope our approach can offer a new direction that could increase the likelihood of candidate therapies being effective in patients.”

In the same press release, Dr. Srivastava emphasizes the scientific advances that have driven the team’s research to this critical point.

“Our study is a really good example of how modern technologies are facilitating the kinds of discoveries that are possible today, but weren’t not so long ago. Using human iPSCs and gene editing allowed us to create a large number of cells that are relevant to the disease process, while powerful machine learning algorithms helped us identify, in a non-biased fashion, the important genes for distinguishing between healthy and diseased cells.”

The full results of this study were published in Science.

You can’t take it if you don’t make it

Biomedical specialist Mamadou Dialio at work in the Cedars-Sinai Biomanufacturing Center. Photo by Cedars-Sinai.

Following the race to develop a vaccine for COVID-19 has been a crash course in learning how complicated creating a new therapy is. It’s not just the science involved, but the logistics. Coming up with a vaccine that is both safe and effective is difficult enough, but then how do you make enough doses of it to treat hundreds of millions of people around the world?

That’s a familiar problem for stem cell researchers. As they develop their products they are often able to make enough cells in their own labs. But as they move into clinical trials where they are testing those cells in more and more people, they need to find a new way to make more cells. And, of course, they need to plan ahead, hoping the therapy is approved by the Food and Drug Administration, so they will need to be able to manufacture enough doses to meet the increased demand.

We saw proof of that planning ahead this week with the news that Cedars-Sinai Medical Center in Los Angeles has opened up a new Biomanufacturing Center.

Dr. Clive Svendsen, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, said in a news release, the Center will manufacture the next generation of drugs and regenerative medicine therapies.

“The Cedars-Sinai Biomanufacturing Center leverages our world-class stem-cell expertise, which already serves scores of clients, to provide a much-needed biomanufacturing facility in Southern California. It is revolutionary by virtue of elevating regenerative medicine and its therapeutic possibilities to an entirely new level-repairing the human body.”

This is no ordinary manufacturing plant. The Center features nine “clean rooms” that are kept free from dust and other contaminants. Everyone working there has to wear protective suits and masks to ensure they don’t bring anything into the clean rooms.

The Center will specialize in manufacturing induced pluripotent stem cells, or iPSCs. Dhruv Sareen, PhD, executive director of the Biolmanufacturing Center, says iPSCs are cells that can be turned into any other kind of cell in the body.

“IPSCs are powerful tools for understanding human disease and developing therapies. These cells enable us to truly practice precision medicine by developing drug treatments tailored to the individual patient or groups of patients with similar genetic profiles.”

The Biomanufacturing Center is designed to address a critical bottleneck in bringing cell- and gene-based therapies to the clinic. After all, developing a therapy is great, but it’s only half the job. Making enough of it to help the people who need it is the other half.

CIRM is funding Dr. Svendsen’s work in developing therapies for ALS and other diseases and disorders.