Stem Cell Agency’s Diane Winokur hailed as Visionary

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CIRM Board member Diane Winokur with CIRM Board Chair Jonathan Thomas at FFB Awards dinner

Generally speaking, I am not a huge fan of gala dinners. It’s not that I don’t like seeing people who do remarkable things getting a well-deserved honor. It’s just that the dinners often go on too long and the food is usually not very good (hey, this is San Francisco, those things matter). But last night’s Foundation Fighting Blindness Visionary Awards in San Francisco was definitely an exception to that rule.

Academy of Sciences Grand Opening

Academy of Sciences in San Francisco

Now it may be that the awards were held in the spectacular Academy of Sciences building in Golden Gate Park, or that the food was delicious. But I think the real reason is that CIRM Board member Diane Winokur was one of those being honored. The other honoree was Dr. Jacque Duncan, an amazing physician at UC San Francisco who has dedicated her life to battling diseases of the retina. The whole event was deeply emotional, and truly inspiring.

Now, Diane is a remarkable woman in many respects. She’s the Board’s Patient Advocate member for ALS (better known as Lou Gehrig’s disease) and multiple sclerosis. But Diane also considers herself a Patient Advocate for all Californians and works hard to help advance the research that could help them. She has a personal connection to vision loss as well; one of her dear friends has lost his sight because of retinitis pigmentosa, and his daughter is losing hers because of the same disease.

Diane at podiumDiane highlighted the work that CIRM is doing to help battle vision destroying diseases; how we have invested more than $125 million in 25 different projects. She talked about the encouraging news from clinical trials we are funding targeting retinitis pigmentosa and dry age-related macular degeneration. Diane said:

“These stem cell clinical trials show that progress is being made. Not as fast as we would like, but as everyone here knows, good science takes time. As a patient advocate on the CIRM Board it’s my role to represent the patient, to be their voice in making decisions about what projects to fund.

Patients are at the heart of everything we do at CIRM, from deciding on funding issues to supporting clinical trials. That’s why I feel so honored to get this award. It comes from an organization, that is equally committed to doing all it can to help people in need, to putting the patient at the center of everything they do.”

It’s clear that patients really are at the heart of the work the Foundation Fighting Blindness (FFB) does. As the organizations CEO Benjamin Yerxa said:

“We support 77 labs in the US, often funding projects no one else would. We do this because we know it is necessary to advance the field. And we are going to keep doing this as best we can, as fast as we can, for as long as we can, because we know so many people are depending on us to help them.”

The other honoree, Jacque Duncan, said after attending many previous Visionary Award dinners and seeing the people being honored it was humbling to be in that company. She talked about the exciting progress being made in the field and the people who are making it possible.

“None of this happens by chance. The path to developing new treatments takes the passion of scientists and doctors, and the commitment of patients to raising the funds needed to do this research. One gala dinner at a time, one Vision Walk at a time. All of this creates community and a common purpose. I truly believe that because of this, tomorrow will be brighter than today.”

Perhaps it’s only appropriate to leave the last word to Diane, who ended her speech saying:

“The Nobel prize winning physicist Heinrich Rohrer once said that science means constantly walking a tightrope between blind faith and curiosity; between expertise and creativity; between bias and openness; between experience and epiphany; in short, between an old today and a new tomorrow.

I believe that working together, CIRM and the Foundation Fighting Blindness, we can create that new tomorrow.”

A road trip to the Inland Empire highlights a hot bed of stem cell research

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Gillian Wilson, Interim Vice Chancellor, Research, UC Riverside welcomes people to the combined Research Roadshow and Patient Advocate event

It took us longer than it should have to pay a visit to California’s Inland Empire, but it was definitely worth the wait. Yesterday CIRM’s Roadshow went to the University of California at Riverside (UCR) to talk to the community there – both scientific and public – about the work we are funding and the progress being made, and to hear from them about their hopes and plans for the future.

As always when we go on the road, we learn so much and are so impressed by everyone’s passion and commitment to stem cell research and their belief that it’s changing the face of medicine as we know it.

Dr. Deborah Deas, the Dean of the UC Riverside School of Medicine and a CIRM Board member, kicked off the proceedings by saying:

“Since CIRM was created in 2004 the agency has been committed to providing the technology and research to meet the unmet needs of the people of California.

On the Board I have been impressed by the sheer range and number of diseases targeted by the research CIRM is funding. We in the Inland Empire are playing our part. With CIRM’s help we have developed a strong program that is doing some exciting work in discovery, education and translational research.”

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CIRM’s Dr. Maria Millan at the Roadshow Patient Advocate event

CIRM’s President and CEO, Dr. Maria T. Millan, and our Board Chair, Jonathan Thomas then gave a quick potted history of CIRM and the projects we are funding. They highlighted how we are creating a pipeline of products from the Discovery, or basic level of research, through to the 45 clinical trials we are funding.

They also talked about the Alpha Clinic Network, based at six highly specialized medical centers around California, that are delivering stem cell therapies and sharing the experiences and knowledge learned from these trials to improve their ability to help patients and advance the field.

Researchers from both UCR then gave a series of brief snapshots of the innovative work they are doing:

  • Looking at new, more efficient and effective ways of expanding the number of human embryonic stem cells in the laboratory to create the high volume of cells needed for therapies.
  • Using biodegradable materials to help repair and regenerate tissue for things as varied as bone and cartilage repair or nerve restoration.
  • Exploring the use of epigenetic factors, things that switch genes on and off, to try and find ways to make repairs inside the body, rather than taking the cells outside the body, re-engineering them and returning them to the body. In essence, using the body as its own lab to manufacture replacement.

Another CIRM Board member, Linda Malkas, talked about the research being done at City of Hope (COH), where she is the associate chair of the Department of Molecular and Cellular Biology, calling it an “engine for discovery that has created the infrastructure and attracted people with an  amazing set of skills to bring forward new therapeutics for patients.”

She talked about how COH is home to one of the first Alpha Clinics that CIRM funded, and that it now has 27 active clinical trials, with seven more pending and 11 more in the pipeline.

“In my opinion this is one of the crown jewels of the CIRM program. CIRM is leading the nation in showing how to put together a network of specialized clinics to deliver these therapies. The National Institutes of Health (NIH) came to CIRM to learn from them and to talk about how to better move the most promising ideas and trials through the system faster and more efficiently.”

Dr. Malkas also celebrated the partnership between COH and UCR, where they are collaborating on 19 different projects, pooling their experience and expertise to advance this research.

Finally, Christine Brown, PhD, talked about her work using chimeric antigen receptor (CAR) T cells to fight cancer stem cells. In this CIRM-funded clinical trial, Dr. Brown hopes to re-engineer a patient’s T cells – a key cell of the immune system – to recognize a target protein on the surface of brain cancer stem cells and kill the tumors.

It was a packed event, with an overflow group watching on monitors outside the auditorium. The questions asked afterwards didn’t just focus on the research being done, but on research that still needs to be done.

One patient advocate couple asked about clinics offering stem cell therapies for Parkinson’s disease, wondering if the therapies were worth spending more than $10,000 on.

Dr. Millan cautioned against getting any therapy that wasn’t either approved by the Food and Drug Administration (FDA) or wasn’t part of a clinical trial sanctioned by the FDA. She said that in the past, these clinics were mostly outside the US (hence the term “stem cell tourism”) but increasingly they are opening up centers here in the US offering unproven and unapproved therapies.

She said there are lots of questions people need to ask before signing up for a clinical trial. You can find those questions here.

The visit was a strong reminder that there is exciting stem cell research taking place all over California and that the Inland Empire is a key player in that research, working on projects that could one day have a huge impact in changing people’s lives, even saving people’s lives.

 

Building a better brain organoid

One of the reasons why it’s so hard to develop treatments for problems in the brain – things like Alzheimer’s, autism and schizophrenia – is that you can’t do an autopsy of a living brain to see what’s going wrong. People tend to object. To get around that, scientists have used stem cells to create models of what’s happening inside the brain. They’re good, but they have their limitations. Now a team at the Salk Institute for Biological Studies has found a way to create a better brain model, and hopefully a faster route to developing new treatments.

For a few years now, scientists have been able to take skin cells from patients with neurodegenerative disorders and turn them into neurons, the kind of brain cell affected by these different diseases. They grow these cells in the lab and turn them into clusters of cells, so-called brain “organoids”, to help us better understand what’s happening inside the brain and even allow us to test medications on them to see if those treatments can help ease some symptoms.

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Human organoid tissue (green) grafted into mouse tissue. Neurons are labeled with red. Credit: Salk Institute

But those models don’t really capture the complexity of our brains – how could they – and so only offer a glimpse into what’s happening inside our skulls.

Now the team at Salk have developed a way of transplanting these organoids into mouse brains, giving them access to oxygen and nutrients that can help them not only survive longer but also display more of the characteristics found in the human brain.

In a news release, CIRM Grantee and professor at Salk’s Laboratory of Genetics, Rusty Gage said this new approach gives researchers a powerful new tool:

“This work brings us one step closer to a more faithful, functional representation of the human brain and could help us design better therapies for neurological and psychiatric diseases.”

The transplanted human brain organoids showed plenty of signs that they were becoming engrafted in the mouse brain:

  • They had blood vessels form in them and blood flowing through them
  • They formed neurons
  • They formed other brain support cells called astrocytes

They also used a series of imaging techniques to confirm that the neurons in the organoid were not just connecting but also sending signals, in essence, communicating with each other.

Abed AlFattah Mansour, a Salk research associate and the paper’s first author, says this is a big accomplishment.

“We saw infiltration of blood vessels into the organoid and supplying it with blood, which was exciting because it’s perhaps the ticket for organoids’ long-term survival. This indicates that the increased blood supply not only helped the organoid to stay healthy longer, but also enabled it to achieve a level of neurological complexity that will help us better understand brain disease.”

A better understanding of what’s going wrong is a key step in being able to develop new treatments to fix the problem.

The study is published in the journal Nature Biotechnology.

CIRM has a double reason to celebrate this work. Not only is the team leader, Rusty Gage, a CIRM grantee but one of the Salk team, Sarah Fernandes, is a former intern in the CIRM Bridges to Stem Cell Research program.

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From left: Sarah Fernandes, Daphne Quang, Stephen Johnston, Sarah Parylak, Rusty Gage, Abed AlFattah Mansour, Hao Li Credit: Salk Institute

Stem Cell Roundup: Backup cells to repair damaged lungs; your unique bowels; and California Cures, 71 ways CIRM is changing the face of medicine

It’s good to have a backup plan

3D illustration of Lungs, medical concept.

Our lungs are amazing things. They take in the air we breathe and move it into our blood so that oxygen can be carried to every part of our body. They’re also surprisingly large. If you were to spread out a lung – and I have no idea why you would want to do that – it would be almost as large as a tennis court.

But lungs are also quite vulnerable organs, relying on a thin layer of epithelial cells to protect them from harmful materials in the air. If those materials damage the lungs our body calls in local stem cells to repair the injury.

Now researchers at the University of Iowa have identified a new group of stem cells, called glandular myoepithelial cells (MECs), that also appear to play an important role in repairing injuries in the lungs.

These MECs seem to be a kind of “reserve” stem cell, waiting around until they are needed and then able to spring into action and develop into new replacement cells in the lungs.

In a news release study author Preston Anderson, said these cells could help develop new approaches to lung regeneration:

“We demonstrated that MECs can self-renew and differentiate into seven distinct cell types in the airway. No other cell type in the lung has been identified with this much stem cell plasticity.”

The study is published in Cell Stem Cell.

Your bowels are unique

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Not to worry, that’s a plastic model of  a bowel

If you are eating as you read this, you should either put your food down or skip this item for now. A new study on bowel cancer says that every tumor is unique and every cell within that tumor is also genetically unique.

Researchers in the UK and Netherlands took samples of normal bowel tissue and cancerous bowel tissue from three people with colorectal cancer. They then grew these in the labs and turned them into mini 3D organoids, so they could study them in greater detail.

In the study, published in the journal Nature, the researchers say they found that tumor cells, not surprisingly, had many more mutations than normal cells, and that not only was each bowel cancer genetically different from each other, but that each cell they studied within that cancer was also different.

In a news release, Prof Sir Mike Stratton, joint corresponding author on the paper from the Wellcome Sanger Institute, said:

“This study gives us fundamental knowledge on the way cancers arise. By studying the patterns of mutations from individual healthy and tumour cells, we can learn what mutational processes have occurred, and then look to see what has caused them. Extending our knowledge on the origin of these processes could help us discover new risk factors to reduce the incidence of cancer and could also put us in a better position to create drugs to target cancer-specific mutational processes directly.”

California Cures: a great title for a great book about CIRM

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CIRM Board Chair Jonathan Thomas (L) and Don Reed

One of the first people I met when I started working at CIRM was Don Reed. He impressed me then with his indefatigable enthusiasm, energy and positive outlook on life. Six years later he is still impressing me.

Don has just completed his second book on stem cell research charting the work of CIRM. It’s called “California Cures: How the California Stem Cell Research Program is Fighting Your Incurable Disease”. It’s a terrific read combining stories about stem cell research with true tales about Al Jolson, Enrico Caruso and how a dolphin named Ernestine burst Don’s ear drum.

On his website, Stem Cell Battles, Don describes CIRM as a “scrappy little stage agency” – I love that – and says:

“No one can predict the pace of science, nor say when cures will come; but California is bringing the fight. Above all, “California Cures” is a call for action. Washington may argue about the expense of health care (and who will get it), but California works to bring down the mountain of medical debt: stem cell therapies to ease suffering and save lives. We have the momentum. We dare not stop short. Chronic disease threatens everyone — we are fighting for your family, and mine!”

 

Celebrating Exciting CIRM-Funded Discovery Research on World Parkinson’s Day

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.


Birgitt Schuele, Parkinson’s Institute

CIRM Grant: Quest Award – Discovery Stage Research

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)


Jeanne Loring, Scripps Research Institute

CIRM Grant: Quest Award – Discovery Stage Research

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)


Justin Cooper-White, Scaled BioLabs Inc.

CIRM Grant: Quest Award – Discovery Stage Research

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).


Xinnan Wang, Stanford University

CIRM Grant: Basic Biology V

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)


Related Blogs:

Gladstone researchers tame toxic protein that carries increased Alzheimer’s risk

With a clinical trial failure rate of 99% over the past 15 years or so, the path to a cure for Alzheimer’s disease is riddled with disappointment. In many cases, candidate therapies looked very promising in pre-clinical animal studies, only to flop when tested in people. Now, a CIRM-funded Nature Medicine study by researchers at the Gladstone Institutes sheds some light on a source of this discrepancy. And more importantly, the study points to a potential treatment strategy that can remove the hallmarks of Alzheimer’s in human brain cells.

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Build up of tau protein (blue) and amyloid-beta (yellow) in and around neurons are hallmarks of the damage caused by Alzheimer’s disease. 
Image courtesy of the National Institute on Aging/National Institutes of Health.

For several decades, researchers have known the ApoE gene can influence the risk for an Alzheimer’s diagnosis in individuals 65 years and older. The gene comes in a few flavors with ApoE3 and ApoE4 differing in only one spot in their DNA sequences. Though nearly identical, the resulting ApoE3 and E4 proteins have very different shapes with differing function. In fact, people who inherit two copies of the ApoE4 gene have a twelve times higher risk for Alzheimer’s compared to those with the more common ApoE3.

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Yadong Huang

To better understand what’s happening at the cellular level, Yadong Huang, PhD and his team at the Gladstone Institutes obtained skin samples from Alzheimer’s donors carrying two copies of the ApoE4 gene and healthy donors with two copies of ApoE3. The skin cells were reprogrammed into induced pluripotent stem cells (iPSCs) and then matured into nerve cells, or neurons.

Compared to ApoE3 cells, the researchers observed that the ApoE4 neurons accumulated higher levels of proteins called p-tau and amyloid beta, which are hallmarks of Alzheimer’s disease. Repeating this same experiment in iPSC-derived mouse neurons showed no difference in the production of amyloid beta levels between the ApoE3 and E4 neurons. This result points to the importance of studying human disease in human cells, as first author Chengzhong Wang, PhD, points out in a press release:

“There’s an important species difference in the effect of apoE4 on amyloid beta. Increased amyloid beta production is not seen in mouse neurons and could potentially explain some of the discrepancies between mice and humans regarding drug efficacy. This will be very important information for future drug development.”

Further experiments aimed to answer a long sought-after question: is it the absence of ApoE3 or the presence of ApoE4 that causes the damaging effects on neurons? Using gene-editing techniques, the team removed both ApoE forms from the donor-derived neurons. The resulting cells appeared healthy but when ApoE4 was added back in, Alzheimer’s-associated problems emerged. This finding points to the toxicity of ApoE4 to neurons.

With this new insight in hand, the team examined what would happen if they converted the ApoE4 form into the ApoE3 form. The team had previously designed molecules, they dubbed “structure correctors”, that physically interact with the ApoE4 protein and cause it to take on the shape of the ApoE3 form found in healthy individuals. When these correctors were added to the ApoE4 neurons, it brought back normal function to the cells.

Given that the structure corrector is a chemical compound that works in human brain cells, it’s tantalizing to think about its possible use as a novel Alzheimer’s drug. And you can bet Dr. Huang and his group are eagerly embarking on that new path.

The moment of truth. A video about the stem cell therapy that could help millions of people going blind.

“No matter how much one prepares, the first patient is always something very special.” That’s how Dr. Mark Humayun describes his feelings as he prepared to deliver a CIRM-funded stem cell therapy to help someone going blind from dry age-related macular degeneration (AMD).

Humayun, an ophthalmologist and stem cell researcher at USC, spent years developing this therapy and so it’s understandable that he might be a little nervous finally getting a chance to see if it works in people.

It’s quite a complicated procedure, involving turning embryonic stem cells into the kind of cells that are destroyed by AMD, placing those cells onto a specially developed synthetic scaffold and then surgically implanting the cells and scaffold onto the back of the eye.

There’s a real need for a treatment for AMD, the leading cause of vision loss in the US. Right now, there is no effective therapy for AMD and some three million Americans are facing the prospect of losing their eyesight.

The first, preliminary, results of this trial were released last week and they were encouraging. You can read about them on our blog.

Thanks to USC you can also see the team that developed and executed this promising approach. They created a video capturing the moment the team were finally taking all that hard work and delivering it where it matters, to the patient.

Watching the video it’s hard not to think you are watching a piece of history, something that has the potential to do more than just offer hope to people losing their vision, it has the potential to stop and even reverse that process.

The video is a salute to the researchers who developed the therapy, and the doctors, nurses and Operating Room team who delivered it. It’s also a salute to the person lying down, the patient who volunteered to be the first to try this. Everyone in that room is a pioneer.

CIRM’s Industry Alliance Program: Facilitating Partnerships to Advance Stem Cell Therapies

Some things are better together. Take for instance macaroni and cheese, eggs and bacon, cookies and ice cream. Each of these things are fine on their own, but together, they become something more powerful and delicious.

The right partnerships can bring out the best in things. At CIRM, we fully embrace this concept. That’s why we’re launching the Industry Alliance Program (IAP). It’s a new partnering opportunity to bring the most promising stem cell, gene therapy, and regenerative medicine programs to market where they can help people with unmet medical needs.

CIRM is the world’s largest stem cell research funding institution dedicated to helping patients by accelerating the development of quality stem cell treatments. We’re currently funding 244 active stem cell research programs including 39 ongoing clinical trials.

The CIRM IAP is designed to give pharma, biotech and VC firms direct access to CIRM’s growing stem cell portfolio. These partners work in the stem cell and regenerative medicine field and will be connected to CIRM-funded scientists working on projects relevant to their interests.

In a news release, CIRM’s President and CEO, Dr. Maria T. Millan, explained:

Maria T. Millan

“The goal of the IAP is to secure industry partnerships and funding for CIRM’s translational and clinical-stage projects. Our Agency provides researchers the initial funding to advance promising projects towards the clinic. Now, we’re going a step further by offering a program that facilitates connections between industry partners and our grantees. These companies can offer support or additional funding needed to give these promising projects the best chance for success and the best chance of helping patients.”

The first two companies to join the IAP are BlueRock Therapeutics and Vivo Capital. BlueRock is a Cambridge, Massachusetts-based company that is pioneering cell therapies for degenerative diseases while Vivo Capital is a global venture capital firm that invests in life sciences and healthcare companies.

CIRM will continue to selectively recruit new partners to the IAP with the goal of building a collaborative network to support the development and commercialization of CIRM-funded programs.

Neil Littman, CIRM’s Director of Business Development, concluded:

Neil Littman

“The IAP is essentially a built-in concierge service for the stem cell space. Our unique vantage-point both inside and outside of California – spanning discovery, translation, and clinical trials – allows us to effectively match CIRM-funded programs with the strategic objectives of our IAP partners.  We’re excited to work with partners such as BlueRock and Vivo who have a demonstrated commitment to advance stem cell-based therapies to the market.”

For more information about CIRM’s new IAP program, visit our website.

Encouraging news about CIRM-funded clinical trial targeting vision loss

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An eye affected by dry age-related macular degeneration

Dry age-related macular degeneration (AMD) is the leading cause of vision loss in the U.S. By 2020 it’s estimated that as many as three million Americans will be affected by the disease. Right now, there is no effective therapy. But that could change. A new CIRM-funded clinical trial is showing promise in helping people battling the disease not just in stabilizing their vision loss, but even reversing it.

In AMD, cells in the retina, the light-sensitive tissue at the back of the eye, are slowly destroyed affecting a person’s central vision. It can make it difficult to do everyday activities such as reading or watching TV and make it impossible for a person to drive.

Researchers at the University of Southern California (USC) Roski Eye Institute at the Keck School of Medicine, and Regenerative Patch Technologies, have developed a therapy using embryonic stem cells that they turned into retinal pigment epithelium (RPE) cells – the kind of cell destroyed by AMD. These cells were then placed on a synthetic scaffold which was surgically implanted in the back of the eye.

Imaging studies showed that the RPE cells appeared to integrate well into the eye and remained in place during follow-up tests 120 to 365 days after implantation.

Encouraging results

Of the five patients enrolled in the Phase 1/2a trial, four maintained their vision in the treated eye, two showed improvement in the stability of their vision, and one patient had a 17-letter improvement in their vision on a reading chart. In addition, there were no serious side effects or unanticipated problems.

There were other indications the implants were proving beneficial.  People with normal vision have the ability to focus their gaze on a single location. People with advanced AMD lose that ability. In this trial, two of the patients recovered stable fixation. These improvements were maintained in follow-up tests.

Abla-8

Abla Creasey, Ph.D., CIRM’S Vice President of Therapeutics and Strategic Infrastructure says even these small benefits are important:

“Having a therapy with a favorable safety profile, that could slow down the progression, or even reverse the vision loss would benefit millions of Americans. That’s why these results, while still in an early stage are encouraging, because the people treated in the trial are ones most severely affected by the disease who have the least potential for visual recovery.”

This study reflects CIRM’s long-term commitment to supporting the most promising stem cell research. The Stem Cell Agency began supporting USC’s Dr. Mark Humayun, the lead inventor of the implant, in 2010 and has been a partner with him and his team since then.

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In a news release Dr. Humayun said they plan to recruit another 15 patients to see if these results hold up:

“Our study shows that this unique stem cell–based retinal implant thus far is well-tolerated, and preliminary results suggest it may help people with advanced dry age-related macular degeneration.”

While the results, published in the journal Science Translational Medicine, are encouraging the researchers caution that this was a very early stage clinical trial, with a small number of patients. They say the next step is to continue to follow the four patients treated in this trial to see if there are any further changes to their vision, and to conduct a larger trial.

 

 

Stem Cell Roundup: Crafty Cancer, Fighting Viruses, and Brainstorm ALS Trial Expands to Canada

TGIF! Here is your weekly dose of stem cell news…

Shapeshifting cancer cells

This week’s awesome stem cell photo comes with a bizarre story and bonus video footage.

New research from Duke has found that some lung cancer cells with errors in transcription factors begin to resemble their nearest relatives – the cells of the stomach and gut. (Credit – Tata Lab, Duke University)

Researchers at Duke University were studying lung tumor samples and discovered something that didn’t quite belong. Inside the lung tumors were miniature parts of the digestive system including the stomach, duodenum and small intestine. It turns out that the lung cancer cells (and cancer cells in general) are super crafty and had turned off the expression of a gene called NKX2-1. This gene is a master switch that tells developing cells to turn into lung cells. Without this command, cells switch their identity and mature into gut tissue instead. By manipulating these master switches, cancer cells are able to develop resistance to chemotherapy and other cancer treatments.

So, what does this bizarre finding mean for cancer research? Purushothama Rao Tata, first author on the Developmental Cell study, provided an answer in a news release:

“Cancer biologists have long suspected that cancer cells could shape shift in order to evade chemotherapy and acquire resistance, but they didn’t know the mechanisms behind such plasticity. Now that we know what we are dealing with in these tumors – we can think ahead to the possible paths these cells might take and design therapies to block them.”

For more cool photos and insights into this study, watch the Duke Univeristy video below.


Secrets to the viral-fighting ability of stem cells uncovered (Todd Dubnicoff)

I’ve been writing about stem cells for many years and thought I knew most of the basic info about these amazing cells. But up until this week, I had no idea that stem cells are known to fight off viral infections much better than other cells. It does makes sense though. Stem cells give rise to and help maintain all the organs and tissues of the body. So, it would be bad news if, let’s say, a muscle stem cell multiplied to repair damaged tissue while carrying a dangerous virus.

How exactly stem cells fend off attacking viruses is a question that has eluded researchers for decades. But this week, results published in Cell by Rockefeller University scientists may provide an answer.

Stem cells lacking their protective genes are susceptible to infection by the dengue virus, in red. (Rockefeller University)

The researchers found that liver cells and stem cells defend themselves against viruses differently. In the presence of a virus, liver cells and most other cells react by releasing large amounts of interferon, a protein that acts as a distress signal to other cells in the vicinity. That signal activates hundreds of genes responsible for attracting protective immune cells to the site of infection.

Stem cells, however, are always in this state of emergency. Even in the absence of interferon, the antiviral genes were activated in stem cells. And when the stem cells were genetically engineering to lack some of the antiviral genes, the cells no longer could stop viral infection.

In a press release, senior author Charles Rice explained the importance of this work:

“By understanding more about this biology in stem cells, we may learn more about antiviral mechanisms in general.”


CIRM-funded clinical trial for ALS now available next door – in Canada (Kevin McCormack)

In kindergarten we are taught that it’s good to share. So, we are delighted that a Phase 3 clinical trial for ALS – also known as Lou Gehrig’s disease – that CIRM is helping fund is now expanding its reach across the border from the U.S. into Canada.

Brainstorm Cell Therapeutics, the company behind the therapy, says it is going to open a clinical trial site in Canada because so many Canadians have asked for it.

The therapy, as we described in a recent blog post, takes mesenchymal stem cells from the patient’s own bone marrow. Those cells are then modified in the lab to be able to churn out specific proteins that can help protect the brain cells attacked by ALS. The cells are then transplanted back into the patient and the hope is they will slow down, maybe even stop the progression of the disease.

Earlier studies showed the therapy was safe and seemed to benefit some patients. Now people with ALS across our northern border will get a chance to see if it really works.

Chaim Lebovits, the president and chief executive officer of BrainStorm, said in a press release:

“Although there are thousands of patients worldwide with ALS, we initially designed the Phase 3 trial to enroll U.S.-based patients only, primarily to make it easier for patient follow-up visits at the six U.S. clinical sites. However, due to an outpouring of inquiry and support from Canadian patients wanting to enroll in the trial, we filed an amendment with the FDA [the U.S. Food and Drug Administration] to allow Canada-based ALS patients to participate.”

We are happy to share.