Breaking the isolation of rare diseases

Rare disease day

Rare Disease Day in Sacramento, California

How can something that affects 30 million Americans, one in ten people in the US, be called rare? But that’s the case with people who have a rare disease. There are around 7,000 different diseases that are categorized as rare because they affect fewer than 200,000 people. Less than five percent of these diseases have a treatment.

That’s why last Wednesday, in cities across the US, members of the rare disease community gathered to call for more support, more research, and more help for families battling these diseases. Their slogan tells their story, ‘Alone we are rare; Together we are strong.’

At the Rare Disease Day rally in Sacramento, California, I met Kerry Rivas. Kerry’s son Donovan has a life-threatening condition called Shprintzen-Goldberg Syndrome. Talk about rare. There are only 70 documented cases of the syndrome worldwide. Just getting a diagnosis for Donovan took years.

DonovanDonovan suffers from a lot of problems but the most serious affect his heart, lungs and spinal cord. Getting him the care he needs is time consuming and expensive and has forced Kerry and her family to make some big sacrifices. Even so they work hard to try and see that Donovan is able to lead as normal a life as is possible.

While the disease Kerry’s son has is rarer than most, everyone at Rare Disease Day had a similar story, and an equal commitment to doing all they can to be an effective advocate. And their voices are being heard.

To honor the occasion the US Food and Drug Administration (FDA) announced it was partnering with the National Organization of Rare Diseases (NORD) to hold listening sessions involving patients and FDA medical reviewers.

In a news release Peter L. Saltonstall, President and CEO of NORD, said:

“These listening sessions will provide FDA review division staff with better insight into what is important to patients in managing their diseases and improving their quality of life. It is important for FDA to understand, from the patient perspective, disease burden, management of symptoms, daily impact on quality of life, and patients’ risk tolerance. Patients and caregivers bring a pragmatic, realistic perspective about what they are willing to deal with in terms of potential risks and benefits for new therapies.”

FDA Commissioner Dr. Scott Gottlieb said his agency is committed to doing everything possible to help the rare disease community:

“Despite our successes, there are still no treatments for the vast proportion of rare diseases or conditions. FDA is committed to do what we can to stimulate the development of more products by improving the consistency and efficiency of our reviews, streamlining our processes and supporting rare disease research.”

At CIRM we are also committed to doing all we can to help the cause. Many of the diseases we are currently funding in clinical trials are rare diseases like ALS or Lou Gehrig’s disease, SCID, spinal cord injury and sickle cell disease.

Many pharmaceutical companies are shy about funding research targeting these diseases because the number of patients involved is small, so the chances of recouping their investment or even making a profit is small.

At CIRM we don’t have to worry about those considerations. Our focus is solely on helping those in need. People like Donovan Rivas.

Friday Roundup: A better kind of blood stem cell transplant; Encouraging news from spinal cord injury trial; Finding an “elusive” cell that could help diabetics

Cool Instagram image of the week:

Pancreatic Progenitors

Diabetes Research Institute scientists have confirmed that the unique stem cells reside within large ducts of the human pancreas. Two such ducts (green) surrounded by three islets (white) are shown. [Diabetes Research Institute Foundation]

Chemo- and radiation-free blood stem cell transplant showing promise

Bubble baby disease, also known as severe combined immunodeficiency (SCID), is an inherited disorder that leaves newborns without an effective immune system. Currently, the only approved treatment for SCID is a blood stem cell transplant, in which the patient’s defective immune system cells are eliminated by chemotherapy or radiation to clear out space for cells from a healthy, matched donor. Even though the disease can be fatal, physicians loathe to perform a stem cell transplant on bubble baby patients:

Shizuru“Physicians often choose not to give chemotherapy or radiation to young children with SCID because there are lifelong effects: neurological impairment, growth delays, infertility, risk of cancer, etc.,” says Judith Shizuru, MD, PhD, professor of medicine at Stanford University.

To avoid these complications, Dr. Shizuru is currently running a CIRM-funded clinical trial testing a gentler approach to prepare patients for blood stem cell transplants. She presented promising, preliminary results of the trial on Tuesday at the annual meeting of Stanford’s Center for Definitive and Curative Medicine.

Trial participants are receiving a protein antibody called CD117 before their stem cell transplant. Previous studies in animals showed that this antibody binds to the surface of blood stem cells and blocks the action of a factor which is required for stem cell survival. This property of CD117 provides a means to get rid of blood stem cells without radiation or chemotherapy.

Early results in two participants indicate that, 6 and 9 months after receiving the CD117 blood stem cell transplants, the donor cells have successfully established themselves in the patients and begun making immune cells.

Spinal cord injury trial reports more promising results:

AsteriasRegular readers of our blog will already know about our funding for the clinical trial being run by Asterias Biotherapeutics to treat spinal cord injuries. The latest news from the company is very encouraging, in terms of both the safety and effectiveness of the treatment.

Asterias is transplanting stem cells into patients who have suffered recent injuries that have left them paralyzed from the neck down. It’s hoped the treatment will restore connections at the injury site, allowing patients to regain some movement and feeling in their hands and arms.

This week the company announced that of the 25 patients they have treated there have been no serious side effects. In addition:

  • Magnetic Resonance Imaging (MRI) scans show that in more than 90 percent of the patients the cells appear to show signs of engraftment
  • At least 75 percent of those treated have recovered at least one motor level, and almost 20 percent have recovered two levels

In a news release, Michael Mulroy, Asterias’ President and CEO, said:

“The positive safety profile to date, the evidence supporting engraftment of the cells post-implantation, and the improvements we are seeing in upper extremity motor function highlight the promising findings coming from this Phase 1/2a clinical trial, which will guide us as we work to design future studies.”

There you are! Finding the “elusive” human pancreatic progenitor cells – the story behind our cool Instagram image of the week.

Don’t you hate it when you lose something and can’t find it? Well imagine the frustration of scientists who were looking for a group of cells they were sure existed but for decades they couldn’t locate them. Particularly as those cells might help in developing new treatments for diabetes.

Diabetes-Research-Institute_University-of-Miami-Miller-School-of-MedicineWell, rest easy, because scientists at the Diabetes Research Institute at the University of Miami finally found them.

In a study, published in Genetic Engineering and Biotechnology News, the researchers show how they found these progenitor cells in the human pancreas, tucked away in the glands and ducts of the organ.

In type 1 diabetes, the insulin-producing cells in the pancreas are destroyed. Finding these progenitor cells, which have the ability to turn into the kinds of cells that produce insulin, means researchers could develop new ways to regenerate the pancreas’ ability to function normally.

That’s a long way away but this discovery could be an important first step along that path.

Scientists repair spinal cord injuries in monkeys using human stem cells

Human neuronal stem cells extend axons (green). (Image UCSD)

An exciting development for spinal cord injury research was published this week in the journal Nature Medicine. Scientists from the University of San Diego School of Medicine transplanted human neural progenitor cells (NPCs) into rhesus monkeys that had spinal cord injuries. These cells, which are capable of turning into other cells in the brain, survived and robustly developed into nerve cells that improved the monkeys’ use of their hands and arms.

The scientists grafted 20 million human NPCs derived from embryonic stem cells into two-week-old spinal cord lesions in the monkeys. These stem cells were delivered with growth factors to improve their survival and growth. The monkeys were also treated with immunosuppressive drugs to prevent their immune system from rejecting the human cells.

After nine months, they discovered that the NPCs had developed into nerve cells within the injury site that extended past the injury into healthy tissue. These nerve extensions are called axons, which allow nerves to transmit electrical signals and instructions to other brain cells. During spinal cord injury, nerve cells and their axon extensions are damaged. Scientists have found it difficult to regenerate these damaged cells because of the inhibitory growth environment created at the injury site. You can compare it to the build-up of scar tissue after a heart attack. The heart has difficulty regenerating healthy heart muscle, which is instead replaced by fibrous scar tissue.

Excitingly, the UCSD team was able to overcome this hurdle in their current study. When they transplanted human NPCs with growth factors into the monkeys, they found that the cells were not affected by the inhibitory environment of the injury and were able to robustly develop into nerve cells and send out axon extensions.

Large numbers of human axons (green) emerge from a lesion/graft sites. Many axons travel along the interface (indicated by arrows) between spinal cord white matter (nerve fibers covered with myelin) and spinal cord gray matter (nerves without the whitish myelin sheathing). Image courtesy of Mark Tuszynski, UC San Diego School of Medicine.

The senior scientist on the study, Dr. Mark Tuszynski, explained how their findings in a large animal model are a huge step forward for the field in a UCSD Health news release:

“While there was real progress in research using small animal models, there were also enormous uncertainties that we felt could only be addressed by progressing to models more like humans before we conduct trials with people. We discovered that the grafting methods used with rodents didn’t work in larger, non-human primates. There were critical issues of scale, immunosuppression, timing and other features of methodology that had to be altered or invented. Had we attempted human transplantation without prior large animal testing, there would have been substantial risk of clinical trial failure, not because neural stem cells failed to reach their biological potential but because of things we did not know in terms of grafting and supporting the grafted cells.”

Dr. Tuszynski is a CIRM-grantee whose earlier research involved optimizing stem cell treatments for rodent models of spinal cord injury. We’ve blogged about that research previously on the Stem Cellar here and here.

Tuszynski recently was awarded a CIRM discovery stage research grant to develop a candidate human neural stem cell line that is optimized to repair the injured spinal cord and can be used in human clinical trials. He expressed cautious optimism about the future of this treatment for spinal cord injury patients emphasizing the need for patience and more research before arriving at clinical trials:

“We seem to have overcome some major barriers, including the inhibitory nature of adult myelin against axon growth. Our work has taught us that stem cells will take a long time to mature after transplantation to an injury site, and that patience will be required when moving to humans. Still, the growth we observe from these cells is remarkable — and unlike anything I thought possible even ten years ago. There is clearly significant potential here that we hope will benefit humans with spinal cord injury.”

Related Links:

How a stem cell transplant may help transform Lucas Lindner’s life

Lucas Lidner was left paralyzed below the chin after a truck accident last May.  Photo: Fox6Now, Milwaukee

On a Sunday morning in early 2016, Lucas Lindner was driving to get some donuts for his grandmother. A deer jumped in front of his truck. Lucas swerved to avoid it and crashed, suffering a severe spinal cord injury that left him paralyzed from the neck down.

Lucas took part in a CIRM-funded clinical trial, becoming just the second person to get 10 million stem cells transplanted into his neck. Since then he has regained some use of his arms and hands. While some patients with spinal cord injuries do experience what is called “spontaneous” recovery, Lucas was not the only person in the trial who experienced an improvement. Asterias Biotherapeutics, the company behind the clinical trial, reported that four of the six patients in the trial “have recovered 2 or more motor levels on at least one side through 12 months, which is more than double the rates of recovery seen in both matched historical controls and published data in a similar population.”

Lucas says his improvement has changed his life.

“I was pretty skeptical after the accident, on being able to do anything, on what was going to happen. But regaining hand function alone gave me everything I pretty much needed or wanted back.”

Lucas can now type 40 words a minute, use a soldering iron and touch his pinkie to his thumb, something he couldn’t do after the accident.

In August of last year Lucas did something else he never imagined he would be able to do, he threw out the first pitch at a Milwaukee Brewers baseball game. At the time, he said “I’m blown away by the fact that I can pitch a ball again.”

Lucas Lindner at the Milwaukee Brewers baseball game.

Now Lucas has his sights set on something even more ambitious. He is going back to school to study IT.

“When I was in 3rd grade a teacher asked what I want to be and I said a neuro-computational engineer. Everyone laughed at me because no one knew what that meant. Now, after what happened to me, I want to be part of advancing the science, helping make injuries like mine a thing of the past.”

Even though he was one of the first people to take part in this clinical trial, Lucas doesn’t think of himself as a pioneer.

“The real pioneers are the scientists who came up with this therapy, who do it because they love it.”

You can read more about Lucas and other patients who’ve participated in CIRM-funded clinical trials in CIRM’s 2017 Annual Report on our website

For more about Lucas and his story, watch this video below from Asterias.

Positive update on Asterias’ SCiStar study for spinal cord injury at TMM 2017

This guest blog is reposted with permission from Signals Blog, published by the Center for Commercialization of Regenerative Medicine (CCRM) in Canada.

With the extensive exploitation of regenerative medicine through the marketing and selling of unapproved stem cell “therapies” online, it was refreshing to hear an update about clinical trials for a legitimate stem cell therapy at the Till & McCulloch Meetings (TMM) in Canada earlier this month.

Dr. Jane Lebkowski, of Asterias, speaking at TMM 2017

Dr. Jane Lebkowski, President of R&D and Chief Scientific Officer at Asterias Biotherapeutics Inc. shared updates from their SCiStar study. This California-based company is currently in an open-label, single-arm Phase 1/2a clinical trial for testing the safety and efficacy of treating several types of spinal cord injuries (SCI) with AST-OPC1s – a type of brain cell called an oligodendrocyte progenitor cell, which they derived from pluripotent stem cells. Earlier this year they reported promising safety results in their first two cohorts of patients and clearance to proceed into additional patients.

Asterias uses a cryopreserved human ESC (embryonic stem cell) line to derive their AST-OPC1s, which they report are a non-homogenous population containing mostly OPCs and some neural progenitor cells. Importantly, they do not observe evidence that any ESCs remain in their differentiated cultures.

Their clinical trial is operating off the heels of extensive nonclinical safety and efficacy studies in over 28 different animal studies in >3,000 rodents and pigs with a unilateral contusion SCI model, as well as data from the first ever human clinical trial with human ESC-derived products previously conducted by Geron.

In their last non-clinical animal model studies of cervical (neck) and thoracic (back) SCI, Asterias showed that as long as they inject cells within the first 30 days of injury they see a persistent reduction in cavity formation at the injury site. They also saw myelination (growth of a protective, insulating sheath around nerve extensions) of nerve cells when AST-OPC1s were injected into myelin-free Shiverer mice, and increased vascularization (blood vessel growth) of injured tissue that persists to nine months post-transplantation. They also have in vitro data to suggest that the injected cells can secrete neurotrophic factors. Importantly, they saw behavioural improvements in their animal models that include “increases in running speed, right forelimb stride length, right forelimb maximal longitudinal deviation, and right rear stride frequency.”

In her talk at TMM, Dr. Lebkowski gave some exciting details about the company’s most recent clinical study. They’ve been delivering their AST-OPC1s to 18-69 year-old patients with C4-C7 spinal cord injury at multiple doses: a low dose of about two million cells and medium at 10 million cells. They give a single injection of either two million, 10 million, or 20 million AST-OPC1s within 21 to 42 days of injury. They have results from patients in the first two cohorts so far, and reported that both two and 10 million cell doses appeared safe 12 months after administration.

Excitingly, patients who received 10 million cells showed signs of functional improvements (in their movement) that have so far persisted up to 12 months after the injection – an improvement of 12.3% on their motor test, equivalent to two full motor scores. This translates to increased arm and hand function and improved independence in activities of daily living at 12 months. Given that these patients were requiring over six hours of home care a day, even small improvements in motor function can have huge impact on their quality of life and independence.

The research community is still waiting to hear preliminary results from the third cohort of patients who received 20 million cells. Asterias is currently recruiting more patients, including those with incomplete spinal cord injury. These studies will be used to inform a larger, double-blind controlled clinical trial that will include more extensive tests of the functional and physiological effects of injecting AST-OPC1s.

This promising work has not been an easy road. It has taken over a decade of thorough and challenging research. The current work was made possible by a $14.3 million investment from the California Institute for Regenerative Medicine, and Dr. Lebkowski estimates that they have spent over $125 million U.S. for this trial. While Asterias covers non-routine medical costs for the patients who enroll, it will take time and more support from government institutions to further test this treatment and, if proven safe and effective, make it financially accessible to all eligible patients.

Returning to my first point about unapproved stem cell therapies, please engage in conversations about “hype and hope” of stem cell therapies with members of the general public, and encourage them to ask their family health team and a scientist before enrolling in any clinical trials advertised online. There are other ways you can keep our industry “honest” here. For more plain language resources on the current status of stem cell therapies, please see here and here.

Samantha Yammine

Samantha is a PhD Candidate studying neural stem cell biology in Dr. Derek van der Kooy’s lab at the University of Toronto. She is also an avid science communicator who uses social media to make science more accessible to everyone. For your daily dose of the fun and trendy side of science, find her online as @SamanthaZY on Twitter and @Science.Sam on Instagram. 

Stanford scientists are growing brain stem cells in bulk using 3D hydrogels

This blog is the final installment in our #MonthofCIRM series. Be sure to check out our other blogs highlighting important advances in CIRM-funded research and initiatives.

Neural stem cells from the brain have promising potential as cell-based therapies for treating neurological disorders such as Alzheimer’s disease, Parkinson’s, and spinal cord injury. A limiting factor preventing these brain stem cells from reaching the clinic is quantity. Scientists have a difficult time growing large populations of brain stem cells in an efficient, cost-effective manner while also maintaining the cells in a stem cell state (a condition referred to as “stemness”).

CIRM-funded scientists from Stanford University are working on a solution to this problem. Dr. Sarah Heilshorn, an associate professor of Materials Science and Engineering at Stanford, and her team are engineering 3D hydrogel technologies to make it easier and cheaper to expand high-quality neural stem cells (NSCs) for clinical applications. Their research was published yesterday in the journal Nature Materials.

Stem Cells in 3D

Similar to how moviegoers prefer to watch the latest Star Wars installment in 3D, compared to the regular screen, scientists are turning to 3D materials called hydrogels to grow large numbers of stem cells. Such an environment offers more space for the stem cells to proliferate and expand their numbers while keeping them happy in their stem cell state.

To find the ideal conditions to grow NSCs in 3D, Heilshorn’s team tested two important properties of hydrogels: stiffness and degradability (or how easy it is to remodel the structure of the hydrogel material). They designed a range of hydrogels, made from proteins with elastic qualities, that varied in these two properties. Interestingly, they found that the stiffness of the material did not have a profound effect on the “stemness” of NSCs. This result contrasts with other types of adult stem cells like muscle stem cells, which quickly differentiate into mature muscle cells when exposed to stiffer materials.

On the other hand, the researchers found that it was crucial for the NSCs to be able to remodel their 3D environment. NSCs maintained their stemness by secreting enzymes that broke down and rearranged the molecules in the hydrogels. If this enzymatic activity was blocked, or if the cells were grown in hydrogels that couldn’t be remodeled easily, NSCs lost their stemness and stopped proliferating. The team tested two other hydrogel materials and found the same results. As long as the NSCs were in a 3D environment they could remodel, they were able to maintain their stemness.

NSCs maintain their stemness in hydrogels that can be remodeled easily. Nestin (green) and Sox2 (red) are markers that indicate “high-quality” NSCs. (Image courtesy of Chris Madl, Stanford)

Caption: NSCs maintain their stemness in hydrogels that can be remodeled easily. Nestin (green) and Sox2 (red) are markers that indicate “high-quality” NSCs. (Images courtesy of Chris Madl)

Christopher Madl, a PhD student in the Heilshorn lab and the first author on the study, explained how remodeling their 3D environment allows NSCs to grow robustly in an interview with the Stem Cellar:

Chris Madl

“In this study, we identified that the ability of the neural stem cells to dynamically remodel the material was critical to maintaining the correct stem cell state. Being able to remodel (or rearrange) the material permitted the cells to contact each other.  This cell-cell contact is responsible for maintaining signals that allow the stem cells to stay in a stem-like state. Our findings allow expansion of neural stem cells from relatively low-density cultures (aiding scale-up) without the use of expensive chemicals that would otherwise be required to maintain the correct stem cell behavior (potentially decreasing cost).”

To 3D and Beyond

When asked what’s next on the research horizon, Heilshorn said two things:

Sarah Heilshorn

“First, we want to see if other stem cell types – for example, pluripotent stem cells – are also sensitive to the “remodel-ability” of materials. Second, we plan to use our discovery to create a low-cost, reproducible material for efficient expansion of stem cells for clinical applications. In particular, we’d like to explore the use of a single material platform that is injectable, so that the same material could be used to expand the stem cells and then transplant them.”

Heilshorn is planning to apply the latter idea to advance another study that her team is currently working on. The research, which is funded by a CIRM Tools and Technologies grant, aims to develop injectable hydrogels containing NSCs derived from human induced pluripotent stem cells to treat mice, and hopefully one day humans, with spinal cord injury. Heilshorn explained,

“In our CIRM-funded studies, we learned a lot about how neural stem cells interact with materials. This lead us to realize that there’s another critical bottleneck that occurs even before the stage of transplantation: being able to generate a large enough number of high-quality stem cells for transplantation. We are developing materials to improve the transplantation of stem cell-derived therapies to patients with spinal cord injuries. Unfortunately, during the transplantation process, a lot of cells can get damaged. We are now creating injectable materials that prevent this cell damage during transplantation and improve the survival and engraftment of NSCs.”

An injectable material that promotes the expansion of large populations of clinical grade stem cells that can also differentiate into mature cells is highly desired by scientists pursuing the development of cell replacement therapies. Heilshorn and her team at Stanford have made significant progress on this front and are hoping that in time, this technology will prove effective enough to reach the clinic.

CIRM-Funded Clinical Trials Targeting Brain and Eye Disorders

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

 This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Our Agency has funded a total of 40 trials since its inception. 23 of these trials were funded after the launch of our Strategic Plan in 2016, bringing us close to the half way point of our goal to fund 50 new clinical trials by 2020.

Today we are featuring CIRM-funded trials in our neurological and eye disorders portfolio.  CIRM has funded a total of nine trials targeting these disease areas, and seven of these trials are currently active. Check out the infographic below for a list of our currently active trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

UCLA scientists begin a journey to restore the sense of touch in paralyzed patients

Yesterday, CIRM-funded scientists at UCLA published an interesting study that sheds light on the development of sensory neurons, a type of nerve cell that is damaged in patients with spinal cord injury. Their early-stage findings could potentially, down the road, lead to the development of stem cell-based treatments that rebuild the sensory nervous system in paralyzed people that have lost their sense of touch.

Dr. Samantha Butler, a CIRM grantee and professor at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, led the study, which was published in the journal eLife.

Restoring sensation

Butler and her team were interested in understanding the basic development of sensory interneurons in the spinal cord. These are nerve cells in the spinal cord that receive sensory signals from the environment outside the body (like heat, pain and touch) and relay these signals to the brain where the senses are then perceived.

Developing spinal cord injury treatments often focus on the loss of movement caused by damage to the motor neurons in the spine that control our muscles. However, the damage caused to sensory neurons in the spine can be just as debilitating to people with paralysis. Without being able to feel whether a surface is hot or cold, paralyzed patients can sustain serious burn injuries.

Butler commented in a UCLA news release that attempting to restoring sensation in paralyzed patients is just as important as restoring movement:

Samantha Butler

“The understanding of sensory interneuron development has lagged far behind that of another class of neurons—called motor neurons—which control the body’s ability to move. This lack in understanding belies the importance of sensation: it is at the core of human experience. Some patients faced with the reality of paralysis place the recovery of the sense of touch above movement.”

BMPs are important for sensory neuron development

To restore sensation in paralyzed patients, scientists need to replace the sensory neurons that are damaged in the spine. To create these neurons, Butler looked to proteins involved in the early development of the spinal cord called bone morphogenetic proteins or BMPs.

BMPs are an important family of signaling proteins that influence development of the embryo. Their signaling can determine the fate or identity of cells including cells that make up the developing spinal cord.

It was previously thought that the concentration of BMPs determined what type of sensory neuron a stem cell would develop into, but Butler’s team found the opposite in their research. By studying developing chick embryos, they discovered that the type, not the concentration, of BMP matters when determining what subtype of sensory neuron is produced. Increasing the amount of a particular BMP in the chick spinal cord only produced more of the same type of sensory interneuron rather than creating a different type.

Increasing the concentration of a certain type of BMP increases the production of the same categories of sensory interneurons (red and green). (Image credit: UCLA)

The scientists confirmed these findings using mouse embryonic stem cells grown in the lab. Interestingly a different set of BMPs were responsible for deciding sensory neuron fate in the mouse stem cell model compared to the chick embryo. But the finding that different BMPs determine sensory neuron identity was consistent.

So what and what’s next?

While this research is still in its early stages, the findings are important because they offer a better understanding of sensory neuron development in the spinal cord. This research also hints at the potential for stem cell-based therapies that replace or restore the function of sensory neurons in paralyzed patients.

Madeline Andrews, the first author of the study, concluded:

“Central nervous system injuries and diseases are particularly devastating because the brain and spinal cord are unable to regenerate. Replacing damaged tissue with sensory interneurons derived from stem cells is a promising therapeutic strategy. Our research, which provides key insights into how sensory interneurons naturally develop, gets us one step closer to that goal.”

The next stop on the team’s research journey is to understand how BMPs influence sensory neuron development in a human stem cell model. The UCLA news release gave a sneak preview of their plans in the coming years.

“Butler’s team now plans to apply their findings to human stem cells as well as drug testing platforms that target diseased sensory interneurons. They also hope to investigate the feasibility of using sensory interneurons in cellular replacement therapies that may one day restore sensation to paralyzed patients.”

Treatments, cures and clinical trials: an in-person update on CIRM’s progress

Patients and Patient Advocates are at the heart of everything we do at CIRM. That’s why we are holding three free public events in the next few months focused on updating you on the stem cell research we are funding, and our plans for the future.

Right now we have 33 projects that we have funded in clinical trials. Those range from heart disease and stroke, to cancer, diabetes, ALS (Lou Gehrig’s disease), two different forms of vision loss, spinal cord injury and HIV/AIDS. We have also helped cure dozens of children battling deadly immune disorders. But as far as we are concerned we are only just getting started.

Over the course of the next few years, we have a goal of adding dozens more clinical trials to that list, and creating a pipeline of promising therapies for a wide range of diseases and disorders.

That’s why we are holding these free public events – something we try and do every year. We want to let you know what we are doing, what we are funding, how that research is progressing, and to get your thoughts on how we can improve, what else we can do to help meet the needs of the Patient Advocate community. Your voice is important in helping shape everything we do.

The first event is at the Gladstone Institutes in San Francisco on Wednesday, September 6th from noon till 1pm. The doors open at 11am for registration and a light lunch.

Gladstone Institutes

Here’s a link to an Eventbrite page that has all the information about the event, including how you can RSVP to let us know you are coming.

We are fortunate to be joined by two great scientists, and speakers – as well as being CIRM grantees-  from the Gladstone Institutes, Dr. Deepak Srivastava and Dr. Steve Finkbeiner.

Dr. Srivastava is working on regenerating heart muscle after it has been damaged. This research could not only help people recover from a heart attack, but the same principles might also enable us to regenerate other organs damaged by disease. Dr. Finkbeiner is a pioneer in diseases of the brain and has done ground breaking work in both Alzheimer’s and Huntington’s disease.

We have two other free public events coming up in October. The first is at UC Davis in Sacramento on October 10th (noon till 1pm) and the second at Cedars-Sinai in Los Angeles on October 30th (noon till 1pm). We will have more details on these events in the coming weeks.

We look forward to seeing you at one of these events and please feel free to share this information with anyone you think might be interested in attending.

Stem cell stories that caught our eye: skin grafts fight diabetes, reprogramming the immune system, and Asterias expands spinal cord injury trial sites

Here are the stem cell stories that caught our eye this week.

Skin grafts fight diabetes and obesity.

An interesting new gene therapy strategy for fighting type 1 diabetes and obesity surfaced this week. Scientists from the University of Chicago made genetically engineered skin grafts that secrete a peptide hormone called glucagon-liked peptide-1 (GLP-1). This peptide is released by cells in the intestine and can lower blood sugar levels by stimulating pancreatic islet cells to secrete insulin (a hormone that promotes the absorption of glucose from the blood).

The study, which was published in the journal Cell Stem Cell, used CRISPR gene editing technology to introduce a mutation to the GLP-1 gene in mouse and human skin stem cells. This mutation stabilized the GLP-1 peptide, allowing it to hang around in the blood for longer. The team matured these stem cells into skin grafts that secreted the GLP-1 into the bloodstream of mice when treated with a drug called doxycycline.

When fed a high-fat diet, mice with a skin graft (left), genetically altered to secrete GLP-1 in response to the antibiotic doxycycline, gained less weight than normal mice (right). (Image source: Wu Laboratory, the University of Chicago)

On a normal diet, mice that received the skin graft saw a rise in their insulin levels and a decrease in their blood glucose levels, proving that the gene therapy was working. On a high fat diet, mice with the skin graft became obese, but when they were treated with doxycycline, GLP-1 secreted from their grafts reduced the amount of weight gain. So not only does their engineered skin graft technology look like a promising new strategy to treat type 1 diabetes patients, it also could be used to control obesity. The beauty of the technology is in its simplicity.

An article in Genetic Engineering and Biotechnology News that covered this research explained that Xiaoyang Wu, the senior author on the study, and his team “worked with skin because it is a large organ and easily accessible. The cells multiply quickly and are easily transplanted. And, transplanted cells can be removed, if needed. “Skin is such a beautiful system,” Wu says, noting that its features make it a perfect medium for testing gene therapies.”

Wu concluded that, “This kind of therapy could be potentially effective for many metabolic disorders.” According to GenBio, Wu’s team “is now testing the gene-therapy technique in combination with other medications.” They also hope that a similar strategy could be used to treat patients that can’t make certain proteins like in the blood clotting disorder hemophilia.

How to reprogram your immune system (Kevin McCormack)

When your immune system goes wrong it can cause all manner of problems, from type 1 diabetes to multiple sclerosis and cancer. That’s because an overactive immune system causes the body to attack its own tissues, while an underactive one leaves the body vulnerable to outside threats such as viruses. That’s why scientists have long sought ways to correct those immune dysfunctions.

Now researchers at the Gladstone Institutes in San Francisco think they have found a way to reprogram specific cells in the immune system and restore a sense of health and balance to the body. Their findings are published in the journal Nature.

The researchers identified a drug that targets effector T cells, which get our immune system to defend us against outside threats, and turns them into regulatory T cells, which control our immune system and stops it from attacking our own body.

Why would turning one kind of T cell into another be helpful? Well, in some autoimmune diseases, the effector T cells become overly active and attack healthy tissues and organs, damaging and even destroying them. By converting them to regulatory T cells you can prevent that happening.

In addition, some cancers can hijack regulatory T cells and suppress the immune system, allowing the disease to spread. By turning those cells into effector T cells, you can boost the immune system and give it the strength to fight back and, hopefully, kill the cancer.

In a news release, Gladstone Senior Investigator Sheng Ding, the lead scientists on the study, said their findings could have several applications:

“Our findings could have a significant impact on the treatment of autoimmune diseases, as well as on stem cell and immuno-oncology therapies.” 

Gladstone scientists Sheng Ding (right) and Tao Xu (left) discovered how to reprogram cells in our immune system. (Gladstone Institutes)

CIRM-funded spinal cord injury trial expands clinical sites

We have another update from CIRM’s clinical trial front. Asterias Biotherapeutics, which is testing a stem cell treatment for complete cervical (neck) spinal cord injury, is expanding its clinical sites for its CIRM-funded SCiStar Phase 1/2a trial. The company is currently treating patients at six sites in the US, and will be expanding to include two additional sites at Thomas Jefferson University Hospital in Philadelphia and the UC San Diego Medical Center, which is part of the UCSD Health CIRM Alpha Stem Cell Clinic.

In a company news release, Ed Wirth, Chief Medical Officer of Asterias said,

Ed Wirth

“We are excited about the clinical site openings at Thomas Jefferson University Hospital and UC San Diego Health. These sites provide additional geographical reach and previous experience with spinal cord injury trials to our SCiStar study. We have recently reported completion of enrollment in four out of five cohorts in our SCiStar study so we hope these institutions will also participate in a future, larger study of AST-OPC1.”

The news release also gave a recap of the trial’s positive (but still preliminary) results this year and their plans for completing trial enrollment.

“In June 2017, Asterias reported 9 month data from the AIS-A 10 million cell cohort that showed improvements in arm, hand and finger function observed at 3-months and 6-months following administration of AST-OPC1 were confirmed and in some patients further increased at 9-months. The company intends to complete enrollment of the entire SCiStar study later this year, with multiple safety and efficacy readouts anticipated during the remainder of 2017 and 2018.”