ViaCyte Advances Cell Replacement Therapy for High Risk Type 1 Diabetes

San Diego regenerative medicine company ViaCyte announced this week that the Food and Drug Administration (FDA) approved their Investigational New Drug (IND) Application for PEC-Direct, a cell-based therapy to treat patients at risk for severe complications caused by type 1 diabetes. In the US, IND approval is the final regulatory step required before a therapy can be tested in clinical trials.

PEC-Direct is a combination therapy consisting of cells encapsulated in a device that aims to replace the insulin-producing islet cells of the pancreas destroyed in patients with type 1 diabetes. The device contains human stem cell-derived pancreatic progenitor cells that develop into insulin-secreting cells when the device is placed under the patient’s skin. Ports on the surface of the device allow blood vessels from the host to directly contact the cells within, allowing for engraftment of the transplanted cells and for their maturation into islet cells.  These cells can sense and regulate blood glucose levels by secreting the hormones found in islets, including insulin.

ViaCyte’s PEC-Direct device allows a patient’s blood vessels to integrate and make contact with the transplanted cells.

Because PEC-Direct allows for “direct vascularization”, in effect connecting the device to the blood system, patients will need to take immunosuppressive drugs to prevent rejection of the donor cells. ViaCyte is therefore testing this therapy in patients who are at risk for serious complications associated with type 1 diabetes like severe hypoglycemia where a patient’s blood sugar is so low they need immediate medical assistance.

Severe hypoglycemia can occur because people with diabetes must inject insulin to control elevated blood sugar, but the injections can exceed the patients’ needs. The resulting low blood sugar can lead to dizziness, irregular heartbeat, and unconsciousness, even death. In some cases, sufferers are not aware of their hypoglycemia symptoms, putting them at increased risk of these life-threatening complications.

ViaCyte’s President and CEO, Dr. Paul Laikind, explained in a news release,

Paul Laikind

“While insulin therapy transformed type 1 diabetes from a death sentence to a chronic illness, it is far from a cure. Type 1 diabetes patients continue to deal with the daily impact of the disease and remain at risk for often severe long-term complications.  This is especially true for the patients with high-risk type 1 diabetes, who face challenges such as hypoglycemia unawareness and life-threatening severe hypoglycemic episodes.  These patients have a particularly urgent unmet medical need and could benefit greatly from cell replacement therapy.”

Approximately 140,000 people in the US and Canada suffer from this form of high-risk diabetes. These patients qualify for islet transplants from donated cadaver tissue. But because donor islets are in limited supply, ViaCyte Clinical Advisor, Dr. James Shapiro at the University of Alberta, believes PEC-Direct will address this issue by providing an unlimited supply of cells.

“Islet transplants from scarce organ donors have offered great promise for those with unstable, high-risk type 1 diabetes, but the procedure has many limitations.  With an unlimited supply of new islets that the stem cell-derived therapy promises, we have real potential to benefit far more patients with islet cell replacement.”

The company’s preclinical research on PEC-Direct, leading up to the FDA’s IND approval, was funded by a CIRM late stage preclinical grant. ViaCyte now plans to launch a clinical trial this year that will evaluate the safety and efficacy of PEC-Direct in the US and Canada. They will enroll approximately 40 patients at multiple clinical trial centers including the University of Alberta in Edmonton, the University of Minnesota, and UC San Diego. The trial will test whether the device is safe and whether the transplanted cells can produce enough insulin to relieve patients of insulin injections and hypoglycemic events.

ViaCyte has another product called PEC-Encap, a different implantable device that contains the same cells but protects these cells from the patient’s immune system. The device is being tested in a CIRM-funded Phase 1/2a trial, and ViaCyte is currently collaborating with W. L. Gore & Associates to improve the design of PEC-Encap to improve consistency of engraftment in patients.

Creating partnerships to help get stem cell therapies over the finish line

Lewis, Clark, Sacagawea

Lewis & Clark & Sacagawea:

Trying to go it alone is never easy. Imagine how far Lewis would have got without Clark, or the two of them without Sacagawea. Would Batman have succeeded without Robin; Mickey without Minnie Mouse? Having a partner whose skills and expertise complements yours just makes things easier.

That’s why some recent news about two CIRM-funded companies running clinical trials was so encouraging.

Viacyte Gore

First ViaCyte, which is developing an implantable device to help people with type 1 diabetes, announced a collaborative research agreement with W. L. Gore & Associates, a global materials science company. On every level it seems like a natural fit.

ViaCyte has developed a way of maturing embryonic stem cells into an early form of the cells that produce insulin. They then insert those cells into a permeable device that can be implanted under the skin. Inside the device, the cells mature into insulin-producing cells. While ViaCyte has experience developing the cells, Gore has experience in the research, development and manufacturing of implantable devices.

Gore-tex-fabricWhat they hope to do is develop a kind of high-tech version of what Gore already does with its Gore-Tex fabrics. Gore-Tex keeps the rain out but allows your skin to breathe. To treat diabetes they need a device that keeps the immune system out, so it won’t attack the cells inside, but allows those cells to secrete insulin into the body.

As Edward Gunzel, Technical Leader for Gore PharmBIO Products, said in a news release, each side brings experience and expertise that complements the other:

“We have a proven track record of developing and commercializing innovative new materials and products to address challenging implantable medical device applications and solving difficult problems for biologics manufacturers.  Gore and ViaCyte began exploring a collaboration in 2016 with early encouraging progress leading to this agreement, and it was clear to us that teaming up with ViaCyte provided a synergistic opportunity for both companies.  We look forward to working with ViaCyte to develop novel implantable delivery technologies for cell therapies.”

AMD2

How macular degeneration destroys central vision

Then last week Regenerative Patch Technologies (RPT), which is running a CIRM-funded clinical trial targeting age-related macular degeneration (AMD), announced an investment from Santen Pharmaceutical, a Japanese company specializing in ophthalmology research and treatment.

The investment will help with the development of RPT’s therapy for AMD, a condition that affects millions of people around the world. It’s caused by the deterioration of the macula, the central portion of the retina which is responsible for our ability to focus, read, drive a car and see objects like faces in fine details.

RPE

RPT is using embryonic stem cells to produce the support cells, or RPE cells, needed to replace those lost in AMD. Because these cells exist in a thin sheet in the back of the eye, the company is assembling these sheets in the lab by growing the RPE cells on synthetic scaffolds. These sheets are then surgically implanted into the eye.

In a news release, RPT’s co-founder Dennis Clegg says partnerships like this are essential for small companies like RPT:

“The ability to partner with a global leader in ophthalmology like Santen is very exciting. Such a strong partnership will greatly accelerate RPT’s ability to develop our product safely and effectively.”

These partnerships are not just good news for those involved, they are encouraging for the field as a whole. When big companies like Gore and Santen are willing to invest their own money in a project it suggests growing confidence in the likelihood that this work will be successful, and that it will be profitable.

As the current blockbuster movie ‘Beauty and the Beast’ is proving; with the right partner you can not only make magic, you can also make a lot of money. For potential investors those are both wonderfully attractive qualities. We’re hoping these two new partnerships will help RPT and ViaCyte advance their research. And that these are just the first of many more to come.

Stem Cell Stories That Caught Our Eye: Plasticity in the pancreas and two cool stem cell tools added to the research toolbox

There’s more plasticity in the pancreas than we thought. You’re taught a lot of things about the world when you’re young. As you get older, you realize that not everything you’re told holds true and it’s your own responsibility to determine fact from fiction. This evolution in understanding happens in science too. Scientists do research that leads them to believe that biological processes happen a certain way, only to sometimes find, a few years later, that things are different or not exactly what they had originally thought.

There’s a great example of this in a study published this week in Cell Metabolism about the pancreas. Scientists from UC Davis found that the pancreas, which secretes a hormone called insulin that helps regulate the levels of sugar in your blood, has more “plasticity” than was originally believed. In this case, plasticity refers to the ability of a tissue or organ to regenerate itself by replacing lost or damaged cells.

The long-standing belief in this field was that the insulin producing cells, called beta cells, are replenished when beta cells actively divide to create more copies of themselves. In patients with type 1 diabetes, these cells are specifically targeted and killed off by the immune system. As a result, the beta cell population is dramatically reduced, and patients have to go on life-long insulin treatment.

UC Davis researchers have identified another type of insulin-producing cell in the islets, which appears to be an immature beta cell shown in red. (UC Davis)

But it turns out there is another cell type in the pancreas that is capable of making beta cells and they look like a teenage, less mature version of beta cells. The UC Davis team identified these cells in mice and in samples of human pancreas tissue. These cells hangout at the edges of structures called islets, which are clusters of beta cells within the pancreas. Upon further inspection, the scientists found that these immature beta cells can secrete insulin but cannot detect blood glucose like mature beta cells. They also found their point of origin: the immature beta cells developed from another type of pancreatic cell called the alpha cell.

Diagram of immature beta cells from Cell Metabolism.

In coverage by EurekAlert, Dr Andrew Rakeman, the director of discovery research at the Juvenile Diabetes Research Foundation, commented on the importance of this study’s findings and how it could be translated into a new approach for treating type 1 diabetes patients:

“The concept of harnessing the plasticity in the islet to regenerate beta cells has emerged as an intriguing possibility in recent years. The work from Dr. Huising and his team is showing us not only the degree of plasticity in islet cells, but the paths these cells take when changing identity. Adding to that the observations that the same processes appear to be occurring in human islets raises the possibility that these mechanistic insights may be able to be turned into therapeutic approaches for treating diabetes.”

 

Say hello to iPSCORE, new and improved tools for stem cell research. Stem cells are powerful tools to model human disease and their power got a significant boost this week from a new study published in Stem Cell Reports, led by scientists at UC San Diego School of Medicine.

The team developed a collection of over 200 induced pluripotent stem cell (iPS cell) lines derived from people of diverse ethnic backgrounds. They call this stem cell tool kit “iPSCORE”, which stands for iPSC Collection for Omic Research (omics refers to a field of study in biology ending in -omics, such as genomics or proteomics). The goal of iPSCORE is to identify particular genetic variants (unique differences in DNA sequence between people’s genomes) that are associated with specific diseases and to understand why they cause disease at the molecular level.

In an interview with Phys.org, lead scientist on the study, Dr. Kelly Frazer, further explained the power of iPSCORE:

“The iPSCORE collection contains 75 lines from people of non-European ancestry, including East Asian, South Asian, African American, Mexican American, and Multiracial. It includes multigenerational families and monozygotic twins. This collection will enable us to study how genetic variation influences traits, both at a molecular and physiological level, in appropriate human cell types, such as heart muscle cells. It will help researchers investigate not only common but also rare, and even family-specific variations.”

This research is a great example of scientists identifying a limitation in stem cell research and expanding the stem cell tool kit to model diseases in a diverse human population.

A false color scanning electron micrograph of cultured human neuron from induced pluripotent stem cell. Credit: Mark Ellisman and Thomas Deerinck, UC San Diego.

Stem cells that can grow into ANY type of tissue. Embryonic stem cells can develop into any cell type in the body, earning them the classification of pluripotent. But there is one type of tissue that embryonic stem cells can’t make and it’s called extra-embryonic tissue. This tissue forms the supportive tissue like the placenta that allows an embryo to develop into a healthy baby in the womb.

Stem cells that can develop into both extra-embryonic and embryonic tissue are called totipotent, and they are extremely hard to isolate and study in the lab because scientists lack the methods to maintain them in their totipotent state. Having the ability to study these special stem cells will allow scientists to answer questions about early embryonic development and fertility issues in women.

Reporting this week in the journal Cell, scientists from the Salk Institute in San Diego and Peking University in China identified a cocktail of chemicals that can stabilize human stem cells in a totipotent state where they can give rise to either tissue type. They called these more primitive stem cells extended pluripotent stem cells or EPS cells.

Salk Professor Juan Carlos Izpisua Bemonte, co–senior author of the paper, explained the problem their study addressed and the solution it revealed in a Salk news release:

“During embryonic development, both the fertilized egg and its initial cells are considered totipotent, as they can give rise to all embryonic and extra-embryonic lineages. However, the capture of stem cells with such developmental potential in vitro has been a major challenge in stem cell biology. This is the first study reporting the derivation of a stable stem cell type that shows totipotent-like bi-developmental potential towards both embryonic and extra-embryonic lineages.”

Human EPS cells (green) can be detected in both the embryonic part (left) and extra-embryonic parts (placenta and yolk sac, right) of a mouse embryo. (Salk Institute)

Using this new method, the scientists discovered that human EPS stem cells were able to develop chimeric embryos with mouse stem cells more easily than regular embryonic stem cells. First author on the study, Jun Wu, explained why this ability is important:

“The superior chimeric competency of both human and mouse EPS cells is advantageous in applications such as the generation of transgenic animal models and the production of replacement organs. We are now testing to see whether human EPS cells are more efficient in chimeric contribution to pigs, whose organ size and physiology are closer to humans.”

The Salk team reported on advancements in generating interspecies chimeras earlier this year. In one study, they were able to grow rat organs – including the pancreas, heart and eyes – in a mouse. In another study, they grew human tissue in early-stage pig and cattle embryos with the goal of eventually developing ways to generate transplantable organs for humans. You can read more about their research in this Salk news release.

Stem cells stories that caught our eye: switching cell ID to treat diabetes, AI predicts cell fate, stem cell ALS therapy for Canada

Treating diabetes by changing a cell’s identity. Stem cells are an ideal therapy strategy for treating type 1 diabetes. That’s because the disease is caused by the loss of a very specific cell type: the insulin-producing beta cell in the pancreas. So, several groups are developing treatments that aim to replace the lost cells by transplanting stem cell-derived beta cells grown in the lab. In fact, Viacyte is applying this approach in an ongoing CIRM-funded clinical trial.

In preliminary animal studies published late last week, a Stanford research team has shown another approach may be possible which generates beta cells inside the body instead of relying on cells grown in a petri dish. The CIRM-funded Cell Metabolism report focused on alpha cells, another cell type in pancreas which produces the hormone glucagon.

glucagon

Microscopy of islet cells, round clusters of cells found in the pancreas. The brown stained cells are glucagon-producing alpha cells. Credit: Wikimedia Commons

After eating a meal, insulin is critical for getting blood sugar into your cells for their energy needs. But glucagon is needed to release stored up sugar, or glucose, into your blood when you haven’t eaten for a while. The research team, blocked two genes in mice that are critical for maintaining an alpha cell state. Seven weeks after inhibiting the activity of these genes, the researchers saw that many alpha cells had converted to beta cells, a process called direct reprogramming.

Does the same thing happen in humans? A study of cadaver donors who had been recently diagnosed with diabetes before their death suggests the answer is yes. An analysis of pancreatic tissue samples showed cells that produced both insulin and glucagon, and appeared to be in the process of converting from beta to alpha cells. Further genetic tests showed that diabetes donor cells had lost activity in the two genes that were blocked in the mouse studies.

It turns out that there’s naturally an excess of alpha cells so, as team lead Seung Kim mentioned in a press release, this strategy could pan out:

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Seung Kim. Credit: Steve Fisch, Stanford University

“This indicates that it might be possible to use targeted methods to block these genes or the signals controlling them in the pancreatic islets of people with diabetes to enhance the proportion of alpha cells that convert into beta cells.”

Using computers to predict cell fate. Deep learning is a cutting-edge area of computer science that uses computer algorithms to perform tasks that border on artificial intelligence. From beating humans in a game of Go to self-driving car technology, deep learning has an exciting range of applications. Now, scientists at Helmholtz Zentrum München in Germany have used deep learning to predict the fate of cells.

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Using deep learning, computers can predict the fate of these blood stem cells.
Credit: Helmholtz Zentrum München.

The study, published this week in Nature Methods, focused on blood stem cells also called hematopoietic stem cells. These cells live in the bone marrow and give rise to all the different types of blood cells. This process can go awry and lead to deadly disorders like leukemia, so scientists are very interested in exquisitely understanding each step that a blood stem cell takes as it specializes into different cell types.

Researchers can figure out the fate of a blood stem cells by adding tags, which glow with various color, to the cell surface . Under a microscope these colors reveal the cells identity. But this method is always after the fact. There no way to look at a cell and predict what type of cell it is turning into. In this study, the team filmed the cells under a microscope as they transformed into different cell types. The deep learning algorithm processed the patterns in the cells and developed cell fate predictions. Now, compared to the typical method using the glowing tags, the researchers knew the eventual cell fates much sooner. The team lead, Carsten Marr, explained how this new technology could help their research:

“Since we now know which cells will develop in which way, we can isolate them earlier than before and examine how they differ at a molecular level. We want to use this information to understand how the choices are made for particular developmental traits.”

Stem cell therapy for ALS seeking approval in Canada. (Karen Ring) Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease that kills off the nerve cells responsible for controlling muscle movement. Patients with ALS suffer from muscle weakness, difficulty in speaking, and eventually breathing. There is no cure for ALS and the average life expectancy after diagnosis is just 2 – 5 years. But companies are pursuing stem cell-based therapies in clinical trials as promising treatment options.

One company in particular, BrainStorm Cell Therapeutics based in the US and Israel, is testing a mesenchymal stem cell-based therapy called NurOwn in ALS patients in clinical trials. In their Phase 2 trials, they observed clinical improvements in slowing down the rate of disease progression following the stem cell treatment.

In a recent update from our friends at the Signals Blog, BrainStorm has announced that it is seeking regulatory approval of its NurOwn treatment for ALS patients in Canada. They will be working with the Centre for Commercialization of Regenerative Medicine (CCRM) to apply for a special regulatory approval pathway with Health Canada, the Canadian government department responsible for national public health.

In a press release, BrainStorm CEO Chaim Lebovits, highlighted this new partnership and his company’s mission to gain regulatory approval for their ALS treatment:

“We are pleased to partner with CCRM as we continue our efforts to develop and make NurOwn available commercially to patients with ALS as quickly as possible. We look forward to discussing with Health Canada staff the results of our ALS clinical program to date, which we believe shows compelling evidence of safety and efficacy and may qualify for rapid review under Canada’s regulatory guidelines for drugs to treat serious or life-threatening conditions.”

Stacey Johnson who wrote the Signals Blog piece on this story explained that while BrainStorm is not starting a clinical trial for ALS in Canada, there will be significant benefits if its treatment is approved.

“If BrainStorm qualifies for this pathway and its market authorization request is successful, it is possible that NurOwn could be available for patients in Canada by early 2018.  True access to improved treatments for Canadian ALS patients would be a great outcome and something we are all hoping for.”

CIRM is also funding stem cell-based therapies in clinical trials for ALS. Just yesterday our Board awarded Cedars-Sinai $6.15 million dollars to conduct a Phase 1 trial for ALS patients that will use “cells called astrocytes that have been specially re-engineered to secrete proteins that can help repair and replace the cells damaged by the disease.” You can read more about this new trial in our latest news release.

Partnering with the best to help find cures for rare diseases

As a state agency we focus most of our efforts and nearly all our money on California. That’s what we were set up to do. But that doesn’t mean we don’t also look outside the borders of California to try and find the best research, and the most promising therapies, to help people in need.

Today’s meeting of the CIRM Board was the first time we have had a chance to partner with one of the leading research facilities in the country focusing on children and rare diseases; St. Jude Children’s Researech Hospital in Memphis, Tennessee.

a4da990e3de7a2112ee875fc784deeafSt. Jude is getting $11.9 million to run a Phase I/II clinical trial for x-linked severe combined immunodeficiency disorder (SCID), a catastrophic condition where children are born without a functioning immune system. Because they are unable to fight off infections, many children born with SCID die in the first few years of life.

St. Jude is teaming up with researchers at the University of California, San Francisco (UCSF) to genetically modify the patient’s own blood stem cells, hopefully creating a new blood system and repairing the damaged immune system. St. Jude came up with the method of doing this, UCSF will treat the patients. Having that California component to the clinical trial is what makes it possible for us to fund this work.

This is the first time CIRM has funded work with St. Jude and reflects our commitment to moving the most promising research into clinical trials in people, regardless of whether that work originates inside or outside California.

The Board also voted to fund researchers at Cedars-Sinai to run a clinical trial on ALS or Lou Gehrig’s disease. Like SCID, ALS is a rare disease. As Randy Mills, our President and CEO, said in a news release:

CIRM CEO and President, Randy Mills.

CIRM CEO and President, Randy Mills.

“While making a funding decision at CIRM we don’t just look at how many people are affected by a disease, we also look at the severity of the disease on the individual and the potential for impacting other diseases. While the number of patients afflicted by these two diseases may be small, their need is great. Additionally, the potential to use these approaches in treating other disease is very real. The underlying technology used in treating SCID, for example, has potential application in other areas such as sickle cell disease and HIV/AIDS.”

We have written several blogs about the research that cured children with SCID.

The Board also approved funding for a clinical trial to develop a treatment for type 1 diabetes (T1D). This is an autoimmune disease that affects around 1.25 million Americans, and millions more around the globe.

T1D is where the body’s own immune system attacks the cells that produce insulin, which is needed to control blood sugar levels. If left untreated it can result in serious, even life-threatening, complications such as vision loss, kidney damage and heart attacks.

Researchers at Caladrius Biosciences will take cells, called regulatory T cells (Tregs), from the patient’s own immune system, expand the number of those cells in the lab and enhance them to make them more effective at preventing the autoimmune attack on the insulin-producing cells.

The focus is on newly-diagnosed adolescents because studies show that at the time of diagnosis T1D patients usually have around 20 percent of their insulin-producing cells still intact. It’s hoped by intervening early the therapy can protect those cells and reduce the need for patients to rely on insulin injections.

David J. Mazzo, Ph.D., CEO of Caladrius Biosciences, says this is hopeful news for people with type 1 diabetes:

David Mazzo

David Mazzo

“We firmly believe that this therapy has the potential to improve the lives of people with T1D and this grant helps us advance our Phase 2 clinical study with the goal of determining the potential for CLBS03 to be an effective therapy in this important indication.”

 


Related Links:

Stories that caught our eye: frail bones in diabetics, ethics of future IVF, Alzheimer’s

The connection between diabetes and frail bones uncovered
Fundamentally, diabetes is defined by abnormally high blood sugar levels. But that one defect over time carries an increased risk for a wide range of severe health problems. For instance, compared to healthy individuals, type 2 diabetics are more prone to poorly healing bone fractures – a condition that can dramatically lower one’s quality of life.

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Bones of the healthy animals (top) form larger calluses during healing which lead to stronger repaired bones. Bones of the diabetic mice (bottom) have smaller calluses and the healed bones are more brittle. Image: Stanford University

To help these people, researchers are trying to tease out how diabetes impacts bone health. But it’s been a complicated challenge since there are many factors at play. Is it from potential side effects of diabetes drugs? Or is the increased body weight associated with type 2 diabetes leading to decreased bone density? This week a CIRM-funded team at Stanford pinpointed skeletal stem cells, a type of adult stem cell that goes on to make all the building blocks of the bone, as important pieces to this scientific puzzle.

Reporting in Science Translational Medicine, the team, led by Michael Longaker – co-director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine – found that, compared to healthy animals, type 2 diabetic mice have a reduced number of skeletal stem cells after bone fracture. A study of the local cellular “neighborhood” of these stem cells showed that the diabetic mice also had a reduction in the levels of a protein called hedgehog. Blocking hedgehog activity in healthy mice led to the slow bone healing seen in the diabetic mice. More importantly, boosting hedgehog levels near the site of the fracture in diabetic mice lead to bone healing that was just as good as in the healthy mice.

To see if this result might hold up in humans, the team analyzed hedgehog levels in bone samples retrieved from diabetics and non-diabetics undergoing joint replacement surgeries. Sure enough, hedgehog was depleted in the diabetic bone exactly reflecting the mouse results.

Though more studies will be needed to develop a hedgehog-based treatment in humans, Longaker talked about the exciting big picture implications of this result in a press release:

longaker

Michael Longaker

“We’ve uncovered the reason why some patients with diabetes don’t heal well from fractures, and we’ve come up with a solution that can be locally applied during surgery to repair the break. Diabetes is rampant worldwide, and any improvement in the ability of affected people to heal from fractures could have an enormously positive effect on their quality of life.”

 

Getting the ethics ahead of the next generation of fertility treatments
The Business Insider ran an article this week with a provocative title, “Now is the time to talk about creating humans from stem cells.” I initially read too much into that title because I thought the article was advocating the need to start the push for the cloning of people. Instead, author Rafi Letzter was driving at the importance for concrete, ethical discussion right now about stem cell technologies for fertility treatments that may not be too far off.

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These mice were born from artificial eggs that were made from stem cells in a dish.
It’s great news for infertility specialist but carries many ethical dilemmas. 
(Image: K. Hayashi, Kyushu University)

In particular, he alludes to a paper from October (read our blog about it) that reported the creation of female mouse eggs from stem cells. These eggs were fertilized, implanted into the mother and successfully developed into living mice. What’s more, one set of stem cells were derived from mouse skin samples via the induced pluripotent stem cell method. This breakthrough could one day make it possible for an infertile woman to simply go through a small skin biopsy or mouth swab to generate an unlimited number of eggs for in vitro fertilization (IVF). Just imagine how much more efficient, less invasive and less costly this procedure could be compared to current IVF methods that require multiple hormone injections and retrieval of eggs from a woman’s ovaries.

But along with that hope for couples who have trouble conceiving a child comes a whole host of ethical issues. Here, Letzter refers to a perspective letter published on Wednesday in Science Translation Medicine by scientists and ethicists about this looming challenge for researchers and policymakers.

It’s an important read that lays out the current science, the clinical possibilities and regulatory and ethical questions that must be addressed sooner than later. In an interview with Letzter, co-author Eli Adashi, from the Alpert Medical School at Brown University, warned against waiting too long to heed this call to action:

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Eli Adashi

“Let’s start the [ethical] conversation now. Like all conversations it will be time consuming. And depending how well we do it, and we’ve got to do it well, it will be demanding. It will not be wise to have that conversation when you’re seeing a paper in Science or Nature reporting the complete process in a human. That would not be wise on our collective part. We should be as much as possible ready for that.”

 

 

Tackling Frontotemporal dementia and Alzheimer’s by hitting the same target.
To develop new disease therapies, you usually need to understand what is going wrong at a cellular level. In some cases, that approach leads to the identification of a specific protein that is either missing or in short supply. But this initial step is just half the battle because it may not be practical to make a drug out of the protein itself. So researchers instead search for other proteins or small molecules that lead to an increase in the level of the protein.

A CIRM-funded project at the Gladstone Institutes has done just that for the protein called progranulin. People lacking one copy of the progranulin gene carry an increased risk for  frontotemporal dementia (FTD), a degenerative disease of the brain that is the most common cause of dementia in people under 60 years of age. FTD symptoms are often mistaken for Alzheimer’s. In fact, mutations in progranulin are also associated with Alzheimer’s.

Previous studies have shown that increasing levels of progranulin in animals with diseases that mimic FTP and Alzheimer’s symptoms can reverse symptoms. But little was known how progranulin protein levels were regulated in the cells. Amanda Mason, the lead author on the Journal of Biological Chemistry report, explained in a press release how they tackled this challenge:

“We wanted to know what might regulate the levels of progranulin. Many processes in biology are controlled by adding or removing a small chemical group called phosphate, so we started there.”

These phosphate groups hold a lot of energy in their chemical bonds and can be harnessed to activate or turn off the function of proteins and DNA. The team systematically observed the effects of enzymes that add and remove phosphate groups and zeroed in on one called Ripk1 that leads to increases in progranulin levels. Now the team has set their sights on Ripk1 as another potential target for developing a therapeutic that could be effective against both FTP and Alzheimer’s. Steve Finkbeiner, the team lead, gave a big picture perspective on these promising results:

finkbeiner-profile

Steve Finkbeiner

“This is an exciting finding. Alzheimer’s disease was discovered over 100 years ago, and we have essentially no drugs to treat it. To find a possible new way to treat one disease is wonderful. To find a way that might treat two diseases is amazing.”

 

Don’t Sugar Coat it: A Patient’s Perspective on Type 1 Diabetes

John Welsh

John Welsh

“In the weeks leading up to my diagnosis, I remember making and drinking Kool-Aid at the rate of about a gallon per day, and getting up to pee and drink Kool-Aid several times a night. The exhaustion and constant thirst and the weight loss were pretty scary. Insulin saved my life, and it’s been saving my life every day for the past 40 years.” – John Welsh

 

In honor of diabetes awareness month, we are featuring a patient perspective on what it’s like to live with type 1 diabetes (T1D) and what the future of stem cell research holds in terms of a cure.

T1D is a chronic disease that destroys the insulin producing cells in your pancreas, making it very difficult for your body to maintain the proper levels of sugar in your blood. There is no cure for T1D and patients take daily shots of insulin and closely monitor their blood sugar to stay healthy and alive.

Stem cell research offers an alternative strategy for treating T1D patients by potentially replacing their lost insulin producing cells. We’ve written blogs about ongoing stem cell research for diabetes on the Stem Cellar (here) but we haven’t focused on the patient side of T1D. So today, I’m introducing you to John Welsh, a man whose has lived with T1D since 1976.

John Welsh is a MD/PhD scientist and currently works at a company called Dexcom, which make a continuous glucose monitoring (CGM) device for diabetes patients. He is also an enrolled patient in CIRM-funded stem cell clinical trial (also funded by JDRF) for T1D sponsored by the company ViaCyte. The trial is testing a device containing stem cell-derived pancreatic cells that’s placed under the skin to act as a transplanted pancreas. You can learn more about it here.

I reached out to John to see if he wanted to share his story about living with diabetes. He was not only willing but enthusiastic to speak with me. As you will read later, one of John’s passions is a “good story”. And he sure told me a good one. So before you read on, I recommend grabbing some coffee or tea, going to a quiet room, and taking the time to enjoy his interview.


Q: Describe your career path and your current job.

JW: I went to college at UC Santa Cruz and majored in biochemistry and molecular biology. I then went into the medical scientist training program (combined MD/PhD program) at UC San Diego followed by research positions in cell biology and cancer biology at UC San Francisco and Novartis. I’ve been a medical writer specializing in medical devices for type 1 diabetes since 2009. At Dexcom, I help study the benefits of CGM and get the message out to healthcare professionals.

Q: How has diabetes affected your life and what obstacles do you deal with because of diabetes?

JW: I found out I had T1D at the age of 13, and it’s been a part of my life for 40 years. It’s been a big deal in terms of what I’m not allowed to do and figuring out what would be challenging if I tried. On the other hand, having diabetes is a great motivator on a lot of levels personally, educationally and professionally. Having this disease made me want to learn everything I could about the endocrine system. From there, my interests turned to biology – molecular biology in particular – and understanding how molecules in cells work.

The challenge of having diabetes also motivated me to do things that I might not have thought about otherwise – most importantly, a career that combined science and medicine. Having to stay close to my insulin and insulin-delivery paraphernalia (early on, syringes; nowadays, the pump and glucose monitor) meant that I couldn’t do as many ridiculous adventures as I might have otherwise.

Q: Did your diagnosis motivate you to pursue a scientific career?

JW: Absolutely. If I hadn’t gotten diabetes, I probably would have gone into something like engineering. But my parents were both healthcare professionals, so a career in medicine seemed plausible. The medical scientist MD/PhD training program at UC San Diego was really cool, but very competitive. Having first-hand experience with this disease may have given me an inside track with the admissions process, and that imperative – to understand the disease and how best to manage it – has been a great motivator.

There’s also a nice social aspect to being surrounded by people whose lives are affected by T1D.

Q: Describe your treatment regimen for T1D?

JW: I travel around with two things stuck on my belly, a Medtronic pump and a Dexcom Continuous Glucose Monitor (CGM) sensor. The first is an infusion port that can deliver insulin into my body. The port lasts for about three days after which you have to take it out. The port that lives under the skin surface is nine millimeters long and it’s about as thick as a mechanical pencil lead. The port is connected to a tube and the tube is connected to a pump, which has a reservoir with fast-acting insulin in it.

The insulin pump is pretty magical. It’s conceptually very simple, but it transforms the way a lot of people take insulin. You program it so that throughout the day, it squirts in a tiny bit of basal insulin at the low rate that you want. If you’re just cruising through your day, you get an infusion of insulin at a low basal rate. At mealtimes, you can give yourself an extra squirt of insulin like what happens with normal people’s pancreas. Or if you happen to notice that you have a high sugar level, you can program a correction bolus which will help to bring it back to towards the normal range. The sensor continuously interrogates the glucose concentration in under my skin. If something goes off the rails, it will beep at me.

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Dexcom continuous glucose monitor.

As good as these devices are, they’re not a cure, they’re not perfect, and they’re not cheap, so one of my concerns as a physician and as a patient is making these transformative devices better and more widely available to people with the disease.

Q: What are the negative side effects associated with your insulin pump and sensor?

JW:  If you have an insulin pump, you carry it everywhere because it’s stuck onto you. The pump is on you for three days and it does get itchy. It’s expensive and a bit uncomfortable. And when I take my shirt off, it’s obvious that I have certain devices stuck on me.  This is a big disincentive for some of my type 1 friends, especially those who like to wear clothes without pockets. And every once-in-a-while, the pump will malfunction and you need a backup plan for getting insulin when it breaks.

On the other hand, the continuous glucose monitoring (CGM) is wonderful especially for moms and dads whose kids have T1D. CGM lets parents essentially spy on their kids. You can be on the sidelines watching your kid play soccer and you get a push notification on your phone saying that the glucose concentration is low, or is heading in that direction. The best-case scenario is that this technology helps people avoid dangerous and potentially catastrophic low blood sugars.

Q: Was the decision easy or hard to enroll in the ViaCyte trial?

JW: It was easy! I was very excited to learn about the ViaCyte trial and equally pleased to sign up for it. When I found out about it from a friend, I wanted to sign up for it right away. I went to clinicaltrials.gov and contacted the study coordinator at UC San Diego. They did a screening interview over the phone, and then they brought me in for screening lab work. After I was selected to be in the trial, they implanted a couple of larger devices (about the size of a credit card) under the skin of my lower back, and smaller devices (about the size of a postage stamp) in my arm and lower back to serve as “sentinels” that were taken out after two or three months.

ViaCyte device

ViaCyte device

I’m patient number seven in the safety part of this trial. They put the cell replacement therapy device in me without any pre-medication or immunosuppression. They tested this device first in diabetic mice and found that the stem cells in the device differentiated into insulin producing cells, much like the ones that usually live in the mouse pancreas. They then translated this technology from animal models to human trials and are hoping for the same type of result.

I had the device transplanted in March of 2015, and the plan is for in the final explant procedure to take place next year at the two-year anniversary. Once they take the device out, they will look at the cells under the microscope to see if they are alive and whether they turned into pancreatic cells that secrete insulin.

It’s been no trouble at all having this implant. I do clinic visits regularly where they do a meal challenge and monitor my blood sugar. My experience being a subject in this clinical study has been terrific. I met some wonderful people and I feel like I’m helping the community and advancing the science.

Q: Do you think that stem cell-derived therapies will be a solution for curing diabetes?

JW: T1D is a great target for stem cell therapy – the premise makes a lot of sense — so it’s logical that it’s one of the first ones to enter clinical trials. I definitely think that stem cells could offer a cure for T1D. Even 30 years ago, scientists knew that we needed to generate insulin producing cells somehow, protect them from immunological rejection, and package them up and put them somewhere in the body to act like a normal pancreas. The concept is still a good concept but the devil is in the implementation. That’s why clinical trials like the one CIRM is funding are important to figure these details out and advance the science.

Q: What is your opinion about the importance of stem cell research and advancing stem cell therapies into clinical trials?

JW: Understanding how cells determine their fate is tremendously important. I think that there’s going to be plenty of payoffs for stem cell research in the near term and more so in the intermediate and long term. Stem cell research has my full support, and it’s fun to speculate on how it might address other unmet medical needs. The more we learn about stem cell biology the better.

Q: What advice do you have for other patients dealing with diabetes or who are recently diagnosed?

JW: Don’t give up, don’t be ashamed or discouraged, and gather as much data as you can. Make sure you know where the fast-acting carbohydrates are!

Q: What are you passionate about?

JW: I love a good story, and I’m a fan of biological puzzles. It’s great having a front-row seat in the world of diabetes research, and I want to stick around long enough to celebrate a cure.


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Throwback Thursday: Progress to a Cure for Type 1 Diabetes

Welcome back to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of valuable stem cell stories on our blog. Some of these stories represent crucial advances towards stem cell-based cures for serious diseases and deserve a second look.

novemberawarenessmonthThis week in honor of Diabetes Awareness Month, we are featuring type 1 diabetes (T1D), a chronic disease that destroys the insulin-producing beta cells in your pancreas. Without these important cells, patients cannot maintain the proper levels of glucose, a fancy name for sugar, in their blood and are at risk for many complications including heart disease, blindness, and even death.

Cell replacement therapy is evolving into an attractive option for patients with T1D. Replacing lost beta cells in the pancreas is a more permanent and less burdensome solution than the daily insulin shots (or insulin pumps) that many T1D patients currently take.

So let’s take a look at the past year’s advances in stem cell research for diabetes.

Making Insulin-Producing Cells from Stem Cells and Skin

This year, there were a lot of exciting studies that improved upon previous methods for generating pancreatic beta cells in a dish. Here’s a brief recap of a few of the studies we covered on our blog:

  • Make pancreatic cells from stem cells. Scientists from the Washington University School of Medicine in St. Louis and the Harvard Stem Cell Institute developed a method that makes beta cells from T1D patient-derived induced pluripotent stem cells (iPSCs) that behave very similarly to true beta cells both in a dish and when transplanted into diabetic mice. Their discovery has the potential to offer personalized stem cell treatments for patients with T1D in the near future and the authors of the study predicted that their technology could be ready to test in humans in the next three to five years.
  • Making functional pancreatic cells from skin. Scientists from the Gladstone Institutes used a technique called direct reprogramming to turn human skin cells directly into pancreatic beta cells without having to go all the way back to a pluripotent stem cell state. The pancreatic cells looked and acted like the real thing in a dish (they were able to secrete insulin when exposed to glucose), and they functioned normally when transplanted into diabetic mice. This study is exciting because it offers a new and more efficient method to make functioning human beta cells in mass quantities.

    Functioning human pancreatic cells after they’ve been transplanted into a mouse. (Image: Saiyong Zhu, Gladstone)

    Functioning human pancreatic cells after they’ve been transplanted into a mouse. (Image: Saiyong Zhu, Gladstone)

  • Challenges of stem cell-derived diabetes treatments. At this year’s Ogawa-Yamanaka Stem Cell Award ceremony Douglas Melton, a well-renowned diabetes researcher from Harvard, spoke about the main challenges for developing stem cell-derived diabetes treatments. The first is the need for better control over the methods that make beta cells from stem cells. The second was finding ways to make large quantities of beta cells for human transplantation. The last was finding ways to prevent a patient’s immune system from rejecting transplanted beta cells. Melton and other scientists are already working on improving techniques to make more beta cells from stem cells. As for preventing transplanted beta cells from being attacked by the patient’s immune system, Melton described two possibilities: using an encapsulation device or biological protection to mask the transplanted cells from an attack.

Progress to a Cure: Clinical Trials for Type 1 Diabetes

Speaking of encapsulation devices, CIRM is funding a Phase I clinical trial sponsored by a San Diego-based company called ViaCyte that’s hoping to develop a stem cell-based cure for patients with T1D. The treatment involves placing a small encapsulated device containing stem cell-derived pancreatic precursor cells under the skin of T1D patients. Once implanted, these precursor cells should develop into pancreatic beta cells that can secrete insulin into the patient’s blood stream. The goal of this trial is first to make sure the treatment is safe for patients and second to see if it’s effective in improving a patient’s ability to regulate their blood sugar levels.

To learn more about this exciting clinical trial, watch this fun video made by Youreka Science.

ViaCyte is still waiting on results for their Phase 1 clinical trial, but in the meantime, they are developing a modified version of their original device for T1D called PEC-Direct. This device also contains pancreatic precursor cells but it’s been designed in a way that allows the patient’s blood vessels to make direct connections to the cells inside the device. This vascularization process hopefully will improve the survival and function of the insulin producing beta cells inside the device. This study, which is in the last stage of research before clinical trials, is also being funded by CIRM, and we are excited to hear news about its progress next year.

ViaCyte's PEC-Direct device allows a patient's blood vessels to integrate and make contact with the transplanted beta cells.

ViaCyte’s PEC-Direct device allows a patient’s blood vessels to integrate and make contact with the transplanted beta cells.


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From Pig Parts to Stem Cells: Scientist Douglas Melton Wins Ogawa-Yamanaka Prize for Work on Diabetes

Since the 1920s, insulin injections have remained the best solution for managing type 1 diabetes. Patients with this disease do not make enough insulin – a hormone that regulates the sugar levels in your blood – because the insulin-producing cells, or beta cells, in their pancreas are destroyed.

Back then, it took two tons of pig parts to make eight ounces of insulin, which was enough to treat 10,000 diabetic patients for six months. Biotech and pharmaceutical companies have since developed different types of human insulin treatments that include fast and long acting versions of the hormone. It’s estimated that $22 billion will be spent on developing insulin products for patients this year and that costs will rise to $32 billion in the year 2019.

These costs are necessary to keep insulin-dependent diabetes patients alive and healthy, but what if there was a different, potentially simpler solution to manage diabetes? One that looks to insulin-producing beta cells as the solution rather than daily hormone shots?

Douglas Melton Receives Stem Cell Prize for Work on Diabetes

Harvard scientist Douglas Melton envisions a world where one day, insulin-dependent diabetic patients are given stem cell transplants rather than shots to manage their diabetes. In the 90s, Melton’s son was diagnosed with type 1 diabetes. Motivated by his son’s diagnosis, Melton dedicated the focus of his research on understanding how beta cells develop from stem cells in the body and also in a cell culture dish.

Almost 30 years later, Melton has made huge strides towards understanding the biology of beta cell development and has generated methods to “reprogram” or coax pluripotent stem cells into human beta cells.

Melton was honored for his important contributions to stem cell and diabetes research at the second annual Ogawa-Yamanaka Stem Cell Prize ceremony last week at the Gladstone Institutes. This award recognizes outstanding scientists that are translating stem cell research from the lab to clinical trials in patients.

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Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease, explained why Melton was selected as this year’s prize winner:

Deepak Srivastava, Gladstone Institutes

Deepak Srivastava, Gladstone Institutes

“Doug’s research on genetic markers expressed during pancreas development have led to a reliable way to reprogram stem cells into human beta cells. His work provides the foundation for the ultimate goal of transplantable, patient-specific beta cells.”

 

Making Beta Cells for Patients

During the awards ceremony, Melton discussed his latest work on generating beta cells from human stem cells and how this technology could transform the way insulin-dependent patients are treated.

Douglas Melton, Harvard University.

Douglas Melton, Harvard University.

“I don’t mean to say that this [insulin treatment] isn’t a good idea. That’s keeping these people alive and in good health,” said Melton during his lecture. “What I want to talk about is a different approach. Rather than making more and better insulins and providing them by different medical devices, why not go back to nature’s solution which is the beta cells that makes the insulin?”

Melton first described his initial research on making pancreatic beta cells from embryonic and induced pluripotent stem cells in a culture dish. He described the power of this system for not only modeling diabetes, but also screening for potential drugs, and testing new therapies in animal models.

He also mentioned how he and his colleagues are developing methods to manufacture large amounts of human beta cells derived from pluripotent stem cells for use in patients. They are able to culture stem cells in large spinning flasks that accelerate the growth and development of pluripotent stem cells into billions of human beta cells.

Challenges and Future of Stem-Cell Derived Diabetes Treatments

Melton expressed a positive outlook for the future of stem cell-derived treatments for insulin-dependent diabetes, but he also mentioned two major challenges. The first is the need for better control over the methods that make beta cells from stem cells. These methods could be more efficient and generate higher numbers of beta cells (beta cells make up 16% of stem cell-derived cells using their current culturing methods). The second is preventing an autoimmune attack after transplanting the stem-cell derived beta cells into patients.

Melton and other scientists are already working on improving techniques to make more beta cells from stem cells. As for preventing transplanted beta cells from being attacked by the patient’s immune system, Melton described two possibilities: using an encapsulation device or biological protection to mask the transplanted cells from an attack.

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He mentioned a CIRM-funded clinical trial by ViaCyte, which is testing an encapsulation device that is placed under the skin. The device contains embryonic stem cell-derived pancreatic progenitor cells that develop into beta cells that secrete insulin into the blood stream. The device also prevents the immune system from attacking and killing the beta cells.

Melton also discussed a biological approach to protecting transplanted beta cells. In collaboration with Dan Anderson at MIT, they coated stem cell-derived beta cells in a biomaterial called alginate, which comes from seaweed. They injected alginate microcapsule-containing beta cells into diabetic mice and were able control their blood sugar levels.

At the end of his talk, Melton concluded that he believes that beta cell transplantation in an immunoprotective device containing stem cell-derived cells will have the most benefit for diabetes patients.

Gladstone Youtube video of Douglas Melton’s lecture at the Ogawa-Yamanaka Prize lecture.


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Stem cell stories that caught our eye: healing diabetic ulcers, new spinal cord injury insights & an expanding CRISPR toolbox

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cells heal diabetic foot ulcers in pilot study
Foot ulcers are one of the many long-term complications that diabetics face. About 15 percent of patients develop these open sores which typically appear at the bottom of the foot. In a quarter of these cases, the ulcers lead to serious infection requiring amputation.

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Diabetic foot ulcers are open sores that don’t heal and in many cases leads to amputation. Image source: Izunpharma

But help may be on the horizon in the form of stem cells. Researchers at Mansoura University in Egypt recently presented results of a small study in which 10 patients with diabetic foot ulcers received standard care and another 10 patients received standard care plus injections of mesenchymal stem cells that had been collected from each patient’s own bone marrow. After just six weeks, the stem cell treated group showed a 50% reduction in the foot ulcers while the group with only standard care had a mere 7% reduction.

These superior results with the stem cells were observed even though the group receiving the stem cells had larger foot ulcers to begin with compared to the untreated patients. There are many examples of mesenchymal stem cells’ healing power which make them an extremely popular cell source for hundreds of on-going clinical trials. Mesenchymal stem cells are known to reduce inflammation and increase blood vessel formation, two properties that may be at work to give diabetic foot ulcers the chance to get better.

Medscape Medical News reported on these results which were presented at the 2016 annual meeting of the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting

Suppressing nerve signals to help spinal cord injury victims
Losing the use of one’s limbs is a profound life-altering change for spinal cord injury victims. But their quality of life also suffers tremendously from the loss of bladder control and chronic pain sensations. So much so, victims often say that just improving these secondary symptoms would make a huge improvement in their lives.

While current stem cell-based clinical trials, like the CIRM-funded Asterias study, aim to reverse paralysis by restoring loss nerve signals, recent CIRM-funded animal data published in Cell Stem Cell from UC San Francisco suggest that nerve cells that naturally suppress nerve signals may be helpful for these other symptoms of spinal cord injury.

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Mature inhibitory neuron derived from human embryonic stem cells is shown after successfully migrated and integrated into the injured mouse spinal cord.
Photo by Jiadong Chen, UCSF

It turns out that the bladder control loss and chronic pain may be due to overactive nerve signals. So the lab of Arnold Kriegstein transplanted inhibitory nerve cells – derived from human embryonic stem cells – into mice with spinal cord injuries. The scientists observed that these human inhibitory nerve cells, or interneurons, successfully made working connections in the damaged mouse spinal cords. The rewiring introduced by these interneurons also led to reduced pain behaviors in the mice as well as improvements in bladder control.

 

 

In a Yahoo Finance interview, Kreigstein told reporters he’s eager to push forward with these intriguing results:

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Arnold Kriegstein, UCSF

“As a clinician, I’m very aware of the urgency that’s felt among patients who are often very desperate for treatment. As a result, we’re very interested in accelerating this work toward clinical trials as soon as possible, but there are many steps along the way. We have to demonstrate that this is safe, as well as replicating it in other animals. This involves scaling up the production of these human interneurons in a way that would be compatible with a clinical product.”

 

Expanding the CRISPR toolbox
If science had a fashion week, the relatively new gene editing technology called CRISPR/Cas9 would be sure to dominate the runway. You can think of CRISPR/Cas9 as a protein and RNA complex that acts as a molecular scissor which directly targets and cuts specific sequences of DNA in the human genome. Scientists are using CRISPR/Cas9 to develop innovative biomedical techniques such as removing disease-causing mutations in stem cells in hopes of developing potential treatments for patients suffering from diseases that have no cures.

What’s particularly interesting about the CRISPR/Cas9 system is that the Cas9 protein responsible for cutting DNA is part of a family of CRISPR associated proteins (Cas) that have similar but slightly different functions. Scientists are currently expanding the CRISPR toolbox by exploring the functions of other CRISPR associated proteins for gene editing applications.

A CIRM-funded team at UC Berkeley is particularly interested in a CRISPR protein called C2c2, which is different from Cas9 in that it targets and cuts RNA rather than DNA. Led by Berkeley professor Jennifer Doudna, the team discovered that the CRISPR/C2c2 complex has not just one, but two, distinct ways that it cuts RNA. Their findings were published this week in the journal Nature.

The first way involves creation: C2c2 helps make the guide RNAs that are used to find the RNA molecules that it wants to cut. The second way involves destruction: after the CRISPR/C2c2 complex finds it’s RNAs of choice, C2c2 can then cut and destroy the RNAs.

Doudna commented on the potential applications for this newly added CRISPR tool in a Berkeley News release:

Jennifer-Doudna

Jennifer Doudna: Photo courtesy of iPSCell.com

“This study expands our molecular understanding of C2c2 to guide RNA processing and provides the first application of this novel RNase. C2c2 is essentially a self-arming sentinel that attacks all RNAs upon detecting its target. This activity can be harnessed as an auto-amplifying detector that may be useful as a low-cost diagnostic.”