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.
Since the start of the coronavirus pandemic early last year, scientists all over the world are still trying to better understand SARS-CoV-2, the virus that causes COVID-19. Although the more commonly known symptoms involve respiratory issues, there have been other long term problems observed in recovered patients. These consist of heart issues, fatigue, and neurological issues such as loss of taste and smell and “brain fog”.
To better understand this, Dr. Tariq Rana and a team of researchers at the UC San Diego School of Medicine are using stem cells to create lung and brain organoids to better understand how the virus interacts with the various organ systems and to better develop therapies that block infection. Organoids are 3D models made of cells that can be used to analyze certain features of the human organ being modeled. Although they are far from perfect replicas, they can be used to study physical structure and other characteristics.
The team’s lung and brain organoids produced molecules ACE2 and TMPRSS2, which sit like doorknobs on the outer surfaces of cells. SARS-CoV-2 is able to use these doorknobs to enter cells and establish infection.
Dr. Rana and his team then developed a pseudovirus, a noninfectious version of SARS-CoV-2, and attached a fluorescent label, allowing them to measure how effectively the virus binds in human lung and brain organoids as well as to evaluate the cells’ response. The team was surprised to see an approximately 10-fold higher SARS-CoV-2 infection in lung organoids compared to brain organoids. Additionally, treatment with TMPRSS2 inhibitors reduced infection levels in both organoids.
Besides differences in infection levels, the lung and brain organoids also differed in their responses to the virus. Infected lung organoids pumped out molecules intended to summon help from the immune system while infected brain organoids upped their production of molecules that plays a fundamental role in pathogen recognition and activation of the body’s own immune defenses.
In a news release from UC San Diego Health, Dr. Rana elaborates on the results of his study.
“We’re finding that SARS-CoV-2 doesn’t infect the entire body in the same way. In different cell types, the virus triggers the expression of different genes, and we see different outcomes.”
The next steps for Rana and his team is to develop SARS-CoV-2 inhibitors and test out how well they work in organoid models derived from people of a variety of racial and ethnic backgrounds that represent California’s diverse population. To carry out this research, CIRM awarded Dr. Rana a grant of $250,000, which is part of the $5 million in emergency funding for COVID-19 research that CIRM authorized at the beginning of the pandemic.
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.
Getting older brings with it a mixed bag of items. If you are lucky you can get wiser. If you are not so lucky you can get osteoporosis. But while scientists don’t know how to make you wiser, they have gained some new insights into what makes bones weak and so they might be able to help with the osteoporosis.
Around 200 million people worldwide suffer from osteoporosis, a disease that causes bones to become so brittle that in extreme cases even coughing can lead to a fracture.
Scientists have known for some time that the cells that form the building blocks of our skeletons are found in the bone marrow. They are called mesenchymal stem cells (MSCs) and they have the ability to turn into a number of different kinds of cells, including bone or fat. The keys to deciding which direction the MSCs take are things called epigenetic factors, these basically control which genes are switched on or off and in what order. Now researchers from the UCLA School of Dentistry have identified an enzyme that plays a critical role in that process.
The team found that when the enzyme KDM4B is missing in MSCs those cells are more likely to become fat cells rather than bone cells. Over time that leads to weaker bones and more fractures.
In a news release Dr. Cun-Yu Wang, the lead researcher, said: “We know that bone loss comes with age, but the mechanisms behind extreme cases such as osteoporosis have, up until recently, been very vague.”
To see if they were on the right track the team created a mouse model that lacked KDM4B. Just as they predicted the MSCs in the mouse created more fat than bone, leading to weaker skeletons.
They also looked at mice who were placed on a high fat diet – something known to increase bone loss and weaker bones in people – and found that the diet seemed to reduce KDM4B which in turn produced weaker bones.
In the news release Dr. Paul Krebsbach, Dean of the UCLA School of Dentistry, said the implications for the research are enormous. “The work of Dr. Wang, his lab members and collaborators provides new molecular insight into the changes associated with skeletal aging. These findings are an important step towards what may lead to more effective treatment for the millions of people who suffer from bone loss and osteoporosis.”
The cells in our body are constantly signalling with each other, it’s a critical process by which cells communicate not just with other cells but also with elements within themselves. One of the most important signalling pathways is called Wnt. This plays a key role in early embryonic and later development. But when Wnt signalling goes wrong, it can also help spur the growth of cancer.
In a news release Dr. Mark Mercola, a co-author of a CIRM-funded study – published in the journal Cell Chemical Biology – says this is important: “because it explains why stressed cells cannot regenerate and heal tissue damage. By blocking the ability to respond to Wnt signaling, cellular stress prevents cells from migrating, replicating and differentiating.”
The researchers discovered a compound PAWI-2 that shows promise in blocking the compound that causes this cascade of problems. Co-author Dr. John Cashman says PAWI-2 could lead to treatments in a wide variety of cancers such as pancreatic, breast, prostate and colon cancer.
“As anti-cancer PAWI-2 drug development progresses, we expect PAWI-2 to be less toxic than current therapeutics for pancreatic cancer, and patients will benefit from improved safety, less side effects and possibly with significant cost-savings.”
Speaking of cancer….
Stem cells have many admirable qualities. However, one of their less admirable ones is their ability to occasionally turn into cancer stem cells. Like regular stem cells these have the ability to renew and replicate themselves over time, but as cancer stem cells they use that ability to help fuel the growth and spread of cancer in the body. Now, researchers at U.C. San Diego are trying to better understand how those regular stem cells become cancer stem cells, so they can stop that process.
In a CIRM-funded study Dr. Catriona Jamieson and her team identified two molecules, APOBEC3C and ADAR1, that play a key role in this process.
In a news release Jamieson said: “APOBEC3C and ADAR1 are like the Bonnie and Clyde of pre-cancer stem cells — they drive the cells into malignancy.”
So they studied blood samples from 54 patients with leukemia and 24 without. They found that in response to inflammation, APOBEC3C promotes the rapid production of pre-leukemia stem cells. That in turn enables ADAR1 to go to work, interfering with gene expression in a way that helps those pre-leukemia stem cells turn into leukemia stem cells.
They also found when they blocked the action of ADAR1 or silenced the gene in patient cells in the laboratory, they were able to stop the formation of leukemia stem cells.
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 feature a blog written by two of our fabulous Discovery and Translation team Science Officers, Dr. Kent Fitzgerald and Dr. Ross Okamura.
If you believe that you can know a person by their deeds, the partnership opportunities offered by CIRM illustrate what we, as an agency, believe is the most effective way to deliver on our mission statement, accelerating regenerative medicine treatments to patients with unmet medical needs.
In our past, we have offered awards covering basic biology projects which in turn provided the foundation to produce promising therapies to ease human suffering. But those are only the first steps in an elaborate process.
In order to bring these potential therapies to the clinic, selected drug candidates must next go through a set of activities designed to prepare them for review by the Food and Drug Administration (FDA). For cell therapies, the first formal review is often the Pre- Investigational New Drug Application Consultation or pre-IND. This stage of drug development is commonly referred to as Translational, bridging the gap between our Discovery or early stage research and Clinical Trial programs.
One of our goals at CIRM is to prepare Translational projects we fund for that pre-IND meeting with the FDA, to help them gather data that support the hope this approach will be both safe and effective in patients. Holding this meeting with the FDA is the first step in the often lengthy process of conducting FDA regulated clinical trials and hopefully bringing an approved therapy to patients.
What type of work is required for a promising candidate to move from the Discovery stage into FDA regulated development? To address the needs of Translational science, CIRM offers the Translational Research Project funding opportunity. Activities that CIRM supports at the Translational stage include:
Process Development to allow manufacturing of the candidate therapy under Good Manufacturing Practices (GMP). This is to show that they can manufacture at a large enough scale to treat patients.
Assay development and qualification of measurements to determine whether the drug is being manufactured safely while retaining its curative properties.
Studies to determine the optimal dose and the best way to deliver that dose.
Pilot safety studies looking how the patient might respond after treatment with the drug.
The development of a clinical plan indicating under what rules and conditions the drug might be prescribed to a patient.
These, and other activities supported under our Translational funding program, all help to inform the FDA when they consider what pivotal studies they will require prior to approving an Investigational New Drug (IND) application, the next step in the regulatory approval process.
Since CIRM first offered programs specifically aimed at addressing the Translational stage of therapeutic candidates we have made 41 awards totaling approximately $150 million in funding. To date, 13 have successfully completed and achieved their program goals, while 19 others are still actively working towards meeting their objective. Additionally, three (treating Spina Bifida, Osteonecrosis, and Sickle Cell Disease) of the 13 programs have gone on to receive further CIRM support through our Clinical Stage programs.
During our time administering these awards, CIRM has actively partnered with our grantees to navigate what is required to bring a therapy from the bench to the bedside. CIRM operationalizes this by setting milestones that provide clear definitions of success, specific goals the researchers have to meet to advance the project and also by providing resources for a dedicated project manager to help ensure the project can keep the big picture in mind while executing on their scientific progress.
Throughout all this we partner with the researchers to support them in every possible way. For example, CIRM provides the project teams with Translational Advisory Panels (TAPs, modeled after the CIRM’s Clinical Advisory Panels) which bring in outside subject matter experts as well as patient advocates to help provide additional scientific, regulatory and clinical expertise to guide the development of the program at no additional cost to the grantees. One of the enduring benefits that we hope to provide to researchers and organizations is a practical mastery of translational drug development so that they may continue to advance new and exciting therapies to all patients.
Through CIRM’s strong and continued support of this difficult stage of development, CIRM has developed an internal practical expertise in advancing projects through Translation. We employ our experience to guide our awardees so they can avoid common pitfalls in the development of cell and gene therapies. The end goal is simple, helping to accelerate their path to the clinic and fulfilling the mission of CIRM that has been twice given to us by the voters of California, bringing treatments to patients suffering from unmet medical needs.
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 grantand $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.”
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 take a look at our Review team.
Many people who have to drive every day don’t really think about what’s going on under the hood of their car. As long as the engine works and gets them from A to B, they’re happy. I think the same is true about CIRM’s Review team. Many people don’t really think about all the moving parts that go into reviewing a promising new stem cell therapy.
But that’s a shame, because they are really missing out on watching a truly impressive engine at work.
Just consider the simple fact that since CIRM started about 4,000 companies, groups and individuals have applied to us for funding. Just take a moment to consider that number. Four thousand. Then consider that at no time have there been more than 5 people working in the review team. That’s right. Just 5 people. And more recently there have been substantially fewer. That’s a lot of projects and not a lot of people to review them. So how do they do it? Easy. They’re brilliant.
First, as applications come in they are scrutinized to make sure they meet specific eligibility requirements; do they involve stem cells, is the application complete, is it the right stage of research, is the budget they are proposing appropriate for the work they want to do etc. If they pass that initial appraisal, they then move on to the second round, the Grants Working Group or GWG.
The GWG consists of independent scientific experts from all over the US, all over the world in fact. However, none are from California because we want to ensure there are no possible conflicts of interest. When I say experts, I do mean experts. These are among the top in their field and are highly sought after to do reviews with the National Institutes of Health etc.
Mark Noble, PhD, the Director of the Stem Cell and Regenerative Medicine Institute at the University of Rochester, is a long-time member of the GWG. He says it’s a unique group of people:
“It’s a wonderful scientific education because you come to these meetings and someone is putting in a grant on diabetes and someone’s putting in a grant on repairing the damage to the heart or spinal cord injury or they have a device that will allow you to transplant cells better and there are people in the room that are able to talk knowledgeably about each of these areas and understand how this plays into medicine and how it might work in terms of actual financial development and how it might work in the corporate sphere and how it fits in to unmet medical needs . I don’t know of any comparable review panels like this that have such a broad remit and bring together such a breadth of expertise which means that every review panel you come to you are getting a scientific education on all these different areas, which is great.”
The GWG reviews the projects for scientific merit: does the proposal seem plausible, does the team proposing it have the experience and expertise to do the work etc. The reviewers put in a lot of work ahead of time, not just reviewing the application, but looking at previous studies to see if the new application has evidence to support what this team hope to do, to compare it to other efforts in the same field. There are disagreements, but also a huge amount of respect for each other.
Once the GWG makes its recommendations on which projects to fund and which ones not to, the applications move to the CIRM Board, which has the final say on all funding decisions. The Board is given detailed summaries of each project, along with the recommendations of the GWG and our own CIRM Review team. But the Board is not told the identity of any of the applicants, those are kept secret to avoid even the appearance of any conflict of interest.
The Board is not required to follow the recommendations of the GWG, though they usually do. But the Board is also able to fund projects that the GWG didn’t place in the top tier of applications. They have done this on several occasions, often when the application targeted a disease or disorder that wasn’t currently part of the agency’s portfolio.
So that’s how Review works. The team, led by Dr. Gil Sambrano, does extraordinary work with little fanfare or fuss. But without them CIRM would be a far less effective agency.
The passage of Proposition 14 means we now have a chance to resume full funding of research, which means our Review team is going to be busier than ever. They have already started making changes to the application requirements. To help let researchers know what those changes are we are holding a Zoom webinar tomorrow, Thursday, at noon PST. If you would like to watch you can find it on our YouTube channel. And if you have questions you would like to ask send them to firstname.lastname@example.org
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.We kick off this event with a letter from our the Chair of our Board, Jonathan Thomas.
When voters approved Proposition 14 last November, they gave the Stem Cell Agency a new lease on life and a chance to finish the work we began with the approval of Proposition 71 in 2004. It’s a great honor and privilege. It’s also a great responsibility. But I think looking back at what we have achieved over the last 16 years shows we are well positioned to seize the moment and take CIRM and regenerative medicine to the next level and beyond.
When we started, we were told that if we managed to get one project into a clinical trial by the time our money ran out we would have done a good job. As of this moment we have 68 clinical trials that we have funded plus another 31 projects in clinical trials where we helped fund crucial early stage research. That inexorable march to therapies and cures will resume when we take up our first round of Clinical applications under Prop 14 in March.
But while clinical stage projects are the end game, where we see if therapies really work and are safe in people, there’s so much more that we have achieved since we were created. We have invested $900 million in basic research, creating a pipeline of the most promising stem cell research programs, as well as investing heavily on so-called “translational” projects, which move projects from basic science to where they’re ready to apply to the Food and Drug Administration (FDA) to begin clinical trials.
We have funded more than 1,000 projects, with each one giving us valuable information to help advance the science. Our funding has helped attract some of the best stem cell scientists in the world to California and, because we only fund research in California, it has persuaded many companies to either move here or open offices here to be eligible for our support. We have helped create the Alpha Stem Cell Clinics, a network of leading medical centers around the state that have the experience and expertise to deliver stem cell therapies to patients. All of those have made California a global center in the field.
That result is producing big benefits for the state. An independent Economic Impact Analysis reported that by the end of 2018 we had already helped generate an extra $10.7 billion in new sales revenue and taxes for California, hundreds of millions more in federal taxes and created more than 56,000 new jobs.
Used our support for stem cell research to leverage an additional $12 billion in private funding for the field.
Enrolled more than 2700 patients in CIRM funded clinical trials
In many ways our work is just beginning. We have laid the groundwork, helped enable an extraordinary community of researchers and dramatically accelerated the field. Now we want to get those therapies (and many more) over the finish line and get them approved by the FDA so they can become available to many more people around the state, the country and the world.
We also know that we have to make these therapies available to all people, regardless of their background and ability to pay. We have to ensure that underserved communities, who were often left out of research in the past, are an integral part of this work and are included in every aspect of that research, particularly clinical trials. That’s why we now require anyone applying to us for funding to commit to engaging with underserved communities and to have a written plan to show how they are going to do that.
Over the coming month, you will hear more about some of the remarkable things we have managed to achieve so far and get a better sense of what we hope to do in the future. We know there will be challenges ahead and that not everything we do or support will work. But we also know that with the team we have built at CIRM, the brilliant research community in California and the passion and drive of the patient advocate community we will live up to the responsibility the people of California placed in us when they approved Proposition 14.
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.