Two for 2.0 and Two for us

It began as an ambitious idea; yesterday it became a reality when the CIRM Board approved two projects under CIRM 2.0, one of them a Phase 3 clinical trial for a deadly form of skin cancer.

Just to recap, CIRM 2.0 was introduced by Dr. C. Randal Mills when he took over as President and CEO of the stem cell agency last year. The idea is to speed up the way we work, to get money to the most promising therapies and the best science as quickly as possible. It puts added emphasis on speed, patients and partnerships.

Yesterday our Board approved the first two projects to come before them under this new way of working. One was for almost $18 million for NeoStem, which is planning a Phase 3 clinical trial for metastatic melanoma, a disease that last year alone claimed more than 10,000 lives in the U.S.

This will be the first Phase 3 trial we have funded so clearly it’s quite a milestone for us and for NeoStem. If it proves effective in this trial it could well be approved by the Food and Drug Administration (FDA) for use in melanoma patients. The therapy itself is unique in that it uses the patient’s own tumor cells to create a personalized therapy, one that is designed to engage the patient’s immune system and destroy the cancer.

The Board also approved almost $5 million for Cedars-Sinai in Los Angeles to do the late-stage research needed to apply to the FDA for approval for a clinical trial to treat retinitis pigmentosa (RP). RP is a nasty, degenerative condition that slowly destroys a patient’s vision. There is no cure and no effective therapy.

We are currently funding another clinical trial in this area. The two projects use different types of cells and propose different methods of reducing RP’s devastation. CIRM has a record of trying multiple routes to achieve success when dealing with unmet medical needs.

As Dr. Mills said in a news release, both the therapies approved for funding yesterday support our mission:

“CIRM 2.0 is designed to accelerate the development of treatments for people with unmet medical needs, and these two projects clearly fit that description. With the Board’s approval today we will now get this work up and running within the next 45 days. But that’s just the start. We are not just providing financial support, we are also partnering with these groups to provide expertise, guidance and other kinds of support that these teams need to help them be successful. That’s the promise of CIRM 2.0. Faster funding, better programs and a more comprehensive approach to supporting their progress.”

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

Two seemed to be the number of the day yesterday with the Board welcoming two new members.

Dr. Adriana Padilla is the new Patient Advocate Board member for type 2 Diabetes. She’s a family physician, a member of the University of California, San Francisco-Fresno medical faculty, and an award-winning researcher with expertise in diabetes and its impact on Latino families and the health system in California’s Central Valley. She is also active in the National Hispanic Medical Association (NHMA) and is also a member of the American Diabetes Association.

Dr. Padilla said she hopes her presence will help increase awareness among Latinos of the importance of the work the agency is doing:

“When I was asked about being on the Board I did some research to find out more and it was really touching to learn about some of the exciting work that has been done by the agency and the possibilities that can be done for patients, including those I serve, members of the Latino community.”

Dr. Bob Price is the Associate Vice Chancellor for Research and a Professor of Political Science at U.C. Berkeley. His academic and teaching interests include comparative politics, with a particular interest in the politics of South Africa. This is Dr. Price’s second time on the Board.  He previously served as the alternate to UC Berkeley Chancellor Robert Birgeneau.

Although he has only been off the Board for a little more than a year Dr. Price said he is aware of the big changes that have taken place in that time and is looking forward to being a part of the new CIRM 2.0.

How stimulating! A new way to repair broken bones

For those of us who live in earthquake country the recent devastating quakes in Nepal are a reminder, as if we needed one, of the danger and damage these temblors can cause. Many of those injured in the quake suffered severe bone injuries – broken legs, crushed limbs etc. Repairing those injuries is going to take time and expert medical care. But now a new discovery is opening up the possibility of repairing injuries like this, even regenerating the broken bones, in a more efficient and effective way.

shutterstock_18578173A study published in Scientific Reports  shows that it is possible to regrow bone tissue using protein signals from stem cells. Even more importantly is that this new bone tissue seems to be just as effective, in terms of the quantity and quality of the bone created, as the current methods.

In a news release senior author Todd McDevitt, Ph.D., said this shows we might not even need whole stem cells to regenerate damaged tissue:

“This proof-of-principle work establishes a novel bone formation therapy that exploits the regenerative potential of stem cells. With this technique we can produce new tissue that is completely stem cell-derived and that performs similarly with the gold standard in the field.”

McDevitt – who is now at the Gladstone Institutes thanks to a research leadership award from CIRM  – extracted the proteins that stem cells produce to help regenerate damaged tissues. They then isolated the particular factors they needed to help regenerate bones, in this case bone morphogenetic protein or BMP. That BMP was then transplanted into mice to stimulate bone growth. And it worked.

While this compares favorably to current methods of regenerating or repairing damaged bones it has a few advantages. Current methods rely on getting bones from cadavers and grinding them up to get the growth factors needed to stimulate bone growth. But bones from cadavers can often be in short supply and the quality is highly variable.

As McDevitt says:

“These limitations motivate the need for more consistent and reproducible source material for tissue regeneration. As a renewable resource that is both scalable and consistent in manufacturing, pluripotent stem cells are an ideal solution.”

He says the next step is to build on this research, and try to find ways to make this method even more efficient. If he succeeds he says it could open up new ways of treating devastating injuries such as those sustained by soldiers in battle, or by earthquake victims.

A hopeful sight: therapy for vision loss cleared for clinical trial

Rosalinda Barrero

Rosalinda Barrero, has retinitis pigmentosa

Rosalinda Barrero says people often thought she was rude, or a snob, because of the way she behaved, pretending not to see them or ignoring them on the street. The truth is Rosalinda has retinitis pigmentosa (RP), a nasty disease, one that often attacks early in life and slowly destroys a person’s vision. Rosalinda’s eyes look normal but she can see almost nothing.

“I’ve lived my whole life with this. I told my daughters [as a child] I didn’t like to go Trick or Treating at Halloween because I couldn’t see. I’d trip; I’d loose my candy. I just wanted to stay home.”

Rosalinda says she desperately wants a treatment:

“Because I’m a mom and I would be so much a better mom if I could see. I could drive my daughters around. I want to do my part as a mom.”

Now a promising therapy for RP, funded by the stem cell agency, has been cleared by the Food and Drug Administration (FDA) to start a clinical trial in people.

The therapy was developed by Dr. Henry Klassen at the University of California, Irvine (UCI). RP is a relatively rare, inherited condition in which the light-sensitive cells at the back of the retina, cells that are essential for vision, slowly and progressively degenerate. Eventually it can result in blindness. There is no cure and no effective long-term treatment.

Dr. Klassen’s team will inject patients with stem cells, known as retinal progenitors, to help replace those cells destroyed by the disease and hopefully to save those not yet damaged.

In a news release about the therapy Dr. Klassen said the main goal of this small Phase I trial will be to make sure this approach is safe:

“This milestone is a very important one for our project. It signals a turning point, marking the beginning of the clinical phase of development, and we are all very excited about this project.”

Jonathan Thomas, the Chair of our Board, says that CIRM has invested almost $20 million to help support this work through early stage research and now, into the clinic.

“One of the goals of the agency is to provide the support that promising therapies need to progress and ultimately to get into clinical trials in patients. RP affects about 1.5 million people worldwide and is the leading cause of inherited blindness in the developed world. Having an effective treatment for it would transform people’s lives in extraordinary ways.”

Dr. Klassen says without that support it is doubtful that this work would have progressed as quickly as it has. And the support doesn’t just involve money:

“CIRM has played a critical and essential role in this project. While the funding is extremely important, CIRM also tutors and guides its grantees in the many aspects of translational development at every step of the way, and this accelerates during the later pre-clinical phase where much is at stake.”

This is now the 12th project that we are funding that has been approved by the FDA for clinical trials. It’s cause for optimism, but cautious optimism. These are small scale, early phase trials that in many cases are the first time these therapies have been tested in people. They look promising in the lab. Now it’s time to see if they are equally promising in people.

Considering we didn’t really start funding research until 2007 we have come a long way in a short time. Clearly we still have a long way to go. But the news that Dr. Klassen’s work has been given the go-ahead to take the next, big step, is a hopeful sign for Rosalinda and others with RP that we are at least heading in the right direction.

One of our recent Spotlight on Disease videos features Dr. Klassen and Rosalinda Barrero talking about RP.

This work will be one of the clinical trials being tested in our new Alpha Stem Cell Clinic Network. You can read more about that network here.

Scientists Sink their Teeth into Stem Cell Evolution

Sometimes, answers to biology’s most important questions can be found in the most unexpected of places.

As reported in the most recent issue of the journal Cell Reports, researchers at the University of California, San Francisco (UCSF) and the University of Helsinki describe how studying fossilized rodent teeth has helped them inch closer to grasping the origins of a particular type of stem cell.

Rodents' ever-growing teeth hold clues to the evolution of stem cells, according to a new study.

Rodents’ ever-growing teeth hold clues to the evolution of stem cells, according to a new study.

Understanding the microenvironment that surrounds each stem cell, known as a stem cell niche, is key to grasping the key mechanisms that drive stem cell growth. But as UCSF scientist Ophir Klein explained, many aspects remain a mystery.

“Despite significant recent strides in the field of stem cell biology, the evolutionary mechanisms that give rise to novel stem cell niches remain essentially unexplored,” said Klein, who served as the study’s senior author. “In this study, we have addressed this central question in the fields of evolutionary and developmental biology.”

In this study, Klein and his team focused on the teeth of extinct rodent species. Why? Because many species of rodent—both extinct species and those alive today—have what’s called ‘ever-growing teeth.’

Unlike most mammals, including we humans, the teeth of some rodent species continue to grow as adults—with the help of stem cell ‘reservoir’ hidden inside the root.

And by analyzing the fossilized teeth of extinct rodent species, the researchers could gain some initial insight into how these reservoirs—which were essentially a type of stem cell niche—evolved.

Most stem cell niche studies take cell samples from hair, blood or other live tissue. Teeth, as it turns out, are the only stem cell niches that can be found in fossil form.

In fact, teeth are “the only proxy…for stem cell behavior in the fossil record,” says Klein.

After analyzing more than 3,000 North American rodent fossils that varied in age between 2 and 50 million years ago, the researchers began to notice a trend. The earlier fossils showed short molar teeth. But over the next few million years, the molars began to increase in length. Interestingly, this coincided with the cooling of the climate during the Cenozoic Period. The types of food available in this cooler, drier climate likely became tougher and more abrasive—leading to evolutionary pressures that selected for longer teeth. By 5 million years ago, three-quarters of all species studied had developed the capability for ever-growing teeth.

The team’s models suggest that this trend has little chance of slowing down, and predicts that more than 80% of rodents will adopt the trait of ever-growing teeth.

The next step, says Klein, is to understand the genetic mechanism that is behind the evolutionary change. He and his team, including the study’s first author Vagan Tapaltsyan, will study mice to test the link between the genetics of tooth height and the appearance of stem cell reservoirs.

CIRM-Funded Scientists Build a Better Neuron; Gain New Insight into Motor Neuron Disease

Each individual muscle in our body—no matter how large or how small—is controlled by several types of motor neurons. Damage to one or more types of these neurons can give rise to some of the most devastating motor neuron diseases, many of which have no cure. But now, stem cell scientists at UCLA have manufactured a way to efficiently generate motor neuron subtypes from stem cells, thus providing an improved system with which to study these crucial cells.

“Motor neuron diseases are complex and have no cure; currently we can only provide limited treatments that help patients with some symptoms,” said senior author Bennett Novitch, in a news release. “The results from our study present an effective approach for generating specific motor neuron populations from embryonic stem cells to enhance our understanding of motor neuron development and disease.”

Normally, motor neurons work by transmitting signals between the brain and the body’s muscles. When that connection is severed, the individual loses the ability to control individual muscle movement. This is what happens in the case of amyotrophic lateral sclerosis, or ALS, also known as Lou Gehrig’s disease.

These images reveal the significance of the 'Foxp1 effect.' The Foxp1 transcription factor is crucial to the normal growth and function of motor neurons involved in limb-movement.

These images reveal the significance of the ‘Foxp1 effect.’ The Foxp1 transcription factor is crucial to the normal growth and function of motor neurons involved in limb-movement.

Recent efforts had focused on ways to use stem cell biology to grow motor neurons in the lab. However, such efforts to generate a specific type of motor neuron, called limb-innervating motor neurons, have not been successful. This motor-neuron subtype is particularly affected in ALS, as it supplies nerves to the arms and legs—the regions usually most affected by this deadly disease.

In this study, published this week in Nature Communications, Novitch and his team, including first author Katrina Adams, worked to develop a better method to produce limb-innervating motor neurons. Previous efforts had only had a success rate of about 3 percent. But Novitch and Adams were able to boost that number five-fold, to 20 percent.

Specifically, the UCLA team—using both mouse and human embryonic stem cells—used a technique called ‘transcriptional programming,’ in order to coax these stem cells into become fully functional, limb-innervating motor neurons.

In this approach, which was funded in part by a grant from CIRM, the team added a single transcription factor (a type of protein that regulates gene function), which would then guide the stem cell towards becoming the right type of motor neuron. Here, Novitch, Adams and the team used the Foxp1 transcription factor to do the job.

Normally, Foxp1 is found in healthy, functioning limb-innervating motor neurons. But in stem cell-derived motor neurons, Foxp1 was missing. So the team reasoned that Foxp1 might actually be the key factor to successfully growing these neurons.

Their initial tests of this theory, in which they inserted Foxp1 into a developing chicken spinal cord (a widely used model for neurological research), were far more successful. This result, which is not usually seen with most unmodified stem-cell-derived motor neurons, illustrates the important role played by Foxp1.

The most immediate implications of this research is that now scientists can now use this method to conduct more robust studies that enhance the understanding of how these cells work and, importantly, what happens when things go awry.

Why TED Talks are ChildX’s Play

When the TED (Technology, Entertainment, Design) talks began in 1984 they were intended to be a one-off event. So much for that idea! Today they are a global event, with TED-sponsored conferences held everywhere from Scotland to Tanzania and India. They have also spawned a mini-industry of copycat events. Well, their slogan is “Ideas Worth Spreading” so in a way they only have themselves to blame for having such a great idea.

Dr. Maria Grazia Roncarolo

Dr. Maria Grazia Roncarolo

The latest place for that idea to take root is Stanford, which is holding a TED-style event focused on critical issues facing child and maternal health. The event – April 2nd and 3rd at Stanford – is called ChildX where x = medicine + technology + innovative treatment + wellbeing. ChildX will bring together some of the leading experts in the field for a series of thoughtful, powerful presentations on the biggest problems facing child and maternal health, and the most exciting research aimed at resolving those problems. One of the main tracks during the two-day event is a section on stem cell and gene therapy. It will raise a number of key questions including:

  • What advances have occurred to enable these therapies to move from science fiction less than a decade ago to the promise of next generation transformative therapeutics?
  • In coming years, how will these therapies allow children with presently incurable diseases to become children living free of disease and reaching their maximum potential?

The moderator for that discussion is Dr. Maria Grazia Roncarolo, and you can hear her talking about the most recent advances in the clinical use of stem cell and gene therapies on this podcast. Anytime you get a chance to hear some of the most compelling speakers in their field talk about exciting innovations that could shape the future, it’s worth taking the time to listen.

Goodnight, Stem Cells: How Well Rested Cells Keep Us Healthy

Plenty of studies show that a lack of sleep is nothing but bad news and can contribute to a whole host of health problems like heart disease, poor memory, high blood pressure and obesity.

HSCs_Sleeping_graphic100x100

Even stem cells need rest to stay healthy

In a sense, the same holds true for the stem cells in our body. In response to injury, adult stem cells go to work by dividing and specializing into the cells needed to heal specific tissues and organs. But they also need to rest for long-lasting health. Each cell division carries a risk of introducing DNA mutations—and with it, a risk for cancer. Too much cell division can also deplete the stem cell supply, crippling the healing process. So it’s just as important for the stem cells to assume an inactive, or quiescent, state to maintain their ability to mend the body. Blood stem cells for instance are mostly quiescent and only divide about every two months to renew their reserves.

Even though the importance of this balance is well documented, exactly how it’s achieved is not well understood; that is, until now. Earlier this week, a CIRM-funded research team from The Scripps Research Institute (TSRI) reported on the identification of an enzyme that’s key in controlling the work-rest balance in blood stem cells, also called hematopoietic stem cells (HSCs). Their study, published in the journal Blood, could point the way to drugs that treat anemias, blood cancers, and other blood disorders.

Previous studies in other cell types suggested that this key enzyme, called ItpkB, might play a role in promoting a rested state in HSCs. Senior author Karsten Sauer explained their reasoning for focusing on the enzyme in a press release:

“What made ItpkB an attractive protein to study is that it can dampen activating signaling in other cells. We hypothesized that ItpkB might do the same in HSCs to keep them at rest. Moreover, ItpkB is an enzyme whose function can be controlled by small molecules. This might facilitate drug development if our hypothesis were true.”

Senior author Karsten Sauer is an associate professor at The Scripps Research Institute.

Senior author Karsten Sauer is an associate professor at The Scripps Research Institute.

To test their hypothesis, the team studied HSCs in mice that completely lacked ItpkB. Sure enough, without ItpkB the HSCs got stuck in the “on” position and continually multiplied until the supply of HSCs stores in the bone marrow were exhausted. Without these stem cells, the mice could no longer produce red blood cells, which deliver oxygen to the body or white blood cells, which fight off infection. As a result the animals died due to severe anemia and bone marrow failure. Sauer used a great analogy to describe the result:

“It’s like a car—you need to hit the gas pedal to get some activity, but if you hit it too hard, you can crash into a wall. ItpkB is that spring that prevents you from pushing the pedal all the way through.”

With this new understanding of how balancing stem cell activation and deactivation works, Sauer and his team have their sights set on human therapies:

“If we can show that ItpkB also keeps human HSCs healthy, this could open avenues to target ItpkB to improve HSC function in bone marrow failure syndromes and immunodeficiencies or to increase the success rates of HSC transplantation therapies for leukemias and lymphomas.”

Avoiding drug trial tragedies: new stem cell-based test predicts dangerous drug toxicity

In 2006 Ryan Wilson, a healthy 20 year old Londoner, volunteered for a first-in-human clinical trial to help test the safety of a new drug, TGN1412, intended to treat rheumatoid arthritis and leukemia. The cash he’d get in exchange for his time would help fund his upcoming vacation.

Instead, he nearly died.

Screen Shot 2015-03-11 at 11.37.42 AM

The TGN1412 drug trial disaster got a lot of high profile news coverage in 2006. (image credit: BBC News)

Even though the drug amount injected in his body was 500 times lower than the dose found to be safe in animals, Wilson experienced a catastrophic immune reaction, called a cytokine storm, that led to heart, kidney and liver failure, pneumonia and the loss of his toes and three fingers to dry gangrene. The other five healthy volunteers were also severely injured.

TGN1412’s devastating effect was unfortunately missed in preclinical laboratory and animal studies prior to the human trial. Unlike the pills in your medicine cabinet which are made up of synthesized chemicals, TGN1424 belongs to a growing class of medicines called biologics which come from biological sources such as proteins, DNA, sugars and cells. There is a concern that once a biologic is injected in a patient, the immune system may mount a strong attack all over the body. If that happens, too many immune cells, or white blood cells, are activated and release proteins, called cytokines, which in turn activate more immune cells and the reaction spirals into a dangerous cytokine storm like in Ryan Wilson’s case.

Clearly this tragedy begs for tests that can better predict drug toxicity in humans well before the first trial participants step into the clinic. On Monday a research team from the Imperial College London reported in the journal FASEB that they have done just that using human blood stem cells.

The team’s novel test is not so different than previous ones. Both tests are carried out in a petri dish using two human cell types: white blood cells and endothelial cells, a component of blood vessels. Both tests are also designed to mimic the human immune system’s response to biologics by measuring the release of cytokines.

15MAR11_cytokinestormimages

Endothelial cells grown from blood stem cells. (credit: Imperial College London)

But the Imperial College London team’s test differs from others in one important way: both the white blood cell and endothelial cell types come from the same individual. First they collect a donor’s blood stem cells and specialize them into endothelial cells. Then white blood cells are also collected from the same donor.

The prior tests, on the other hand, rely on cells from two different donors. Because the two cell types aren’t necessarily tissue-matched, the white blood cells may already be primed for an immune response even before a biologic is added to the test. In fact, these prior tests weren’t able to distinguish between a biologic known to cause a limited immune response versus TGN1424, known to cause a cytokine storm. The newly developed test, however, accurately predicts both the toxic cytokine storm caused by TGN1424 and the absence of a response by several approved biologics, such as the breast cancer drug Herceptin.

In a college news release, Jane Mitchell, the senior author on the report, sees the big picture importance of her lab’s work:

“As biological therapies become more mainstream, it’s more likely that drugs being tested on humans for the first time will have unexpected and potentially catastrophic effects. We’ve used adult stem cell technology to develop a laboratory test that could prevent another disaster like the TGN1412 trial.”

Their results also highlight the often-overlooked power of stem cells to not just deliver therapies but to help develop safer ones.

Pioneer’s 25-year struggle to treat blindness

Being a pioneer is never easy. You are charting unknown territory, tackling problems that have defeated others before you. You have to overcome so many obstacles that at times the challenge can seem insurmountable. But for those who succeed in reaching their goal, the rewards can be extraordinary.

Graziella Pellegrini, Center for Regenerative Medicine, University of Modena, Italy

Graziella Pellegrini, Center for Regenerative Medicine, University of Modena, Italy

Last month Italian researcher Graziella Pellegrini saw 25 years of work pay off when a treatment she developed to cure a form of blindness was given approval for sale by the European Commission.

This is quite an achievement as this means her treatment, called Holoclar, is among the first commercial stem therapies in the world (the first was Prochymal, which has been approved in Canada and New Zealand for the treatment of pediatric GVHD. This drug was developed by Osiris, which was led by our current President & CEO, Dr. Randy Mills.)

Holoclar uses stem cells to help stimulate the regrowth of a cornea. It can only be used for certain rare conditions, but that in no way diminishes its importance for patients or significance for the regenerative medicine field as a whole.

Nature recently sat down with Dr. Pellegrini to talk about her work, her struggle, and the many obstacles she had to overcome to get market approval for her work.

The interview makes for fascinating reading, and is a timely reminder why this kind of groundbreaking research never goes quite as quickly, or smoothly, as one would hope.

CIRM currently has a number of projects focused treating different causes of blindness on limbal cells (the kind Dr. Pellegrini worked on) and other forms of blindness; including a project to treat macular degeneration that has been approved for a clinical trial, and a therapy for retinitis pigmentosa that we hope will be approved for a clinical trial later this year.

One-Time, Lasting Treatment for Sickle Cell Disease May be on Horizon, According to New CIRM-Funded Study

For the nearly 1,000 babies born each year in the United States with sickle cell disease, a painful and arduous road awaits them. The only cure is to find a bone marrow donor—an exceedingly rare proposition. Instead, the standard treatment for this inherited blood disorder is regular blood transfusions, with repeated hospitalizations to deal with complications of the disease. And even then, life expectancy is less than 40 years old.

In Sickle Cell Disease, the misshapen red blood cells cause painful blood clots and a host of other complications.

In Sickle Cell Disease, the misshapen red blood cells cause painful blood clots and a host of other complications.

But now, scientists at UCLA are offering up a potentially superior alternative: a new method of gene therapy that can correct the genetic mutation that causes sickle cell disease—and thus help the body on its way to generate normal, healthy blood cells for the rest of the patient’s life. The study, funded in part by CIRM and reported in the journal Blood, offers a great alternative to developing a functional cure for sickle cell disease. The UCLA team is about to begin a clinical trial with another gene therapy method, so they—and their patients—will now have two shots on goal in their effort to cure the disease.

Though sickle cell disease causes dangerous changes to a patient’s entire blood supply, it is caused by one single genetic mutation in the beta-globin gene—altering the shape of the red blood cells from round and soft to pointed and hard, thus resembling a ‘sickle’ shape for which the disease is named. But the UCLA team, led by Donald Kohn, has now developed two methods that can correct the harmful mutation. As he explained in a UCLA news release about the newest technique:

“[These results] suggest the future direction for treating genetic diseases will be by correcting the specific mutation in a patient’s genetic code. Since sickle cell disease was the first human genetic disease where we understood the fundamental gene defect, and since everyone with sickle cell has the exact same mutation in the beta-globin gene, it is a great target for this gene correction method.”

The latest gene correction technique used by the team uses special enzymes, called zinc-finger nucleases, to literally cut out and remove the harmful mutation, replacing it with a corrected version. Here, Kohn and his team collected bone marrow stem cells from individuals with sickle cell disease. These bone marrow stem cells would normally give rise to sickle-shaped red blood cells. But in this study, the team zapped them with the zinc-finger nucleases in order to correct the mutation.

Then, the researchers implanted these corrected cells into laboratory mice. Much to their amazement, the implanted cells began to replicate—into normal, healthy red blood cells.

Kohn and his team worked with Sangamo BioSciences, Inc. to design the zinc-finger nucleases that specifically targeted and cut the sickle-cell mutation. The next steps will involve improving the efficiency and safest of this method in pre-clinical animal models, before moving into clinical trials.

“This is a promising first step in showing that gene correction has the potential to help patients with sickle cell disease,” said UCLA graduate student Megan Hoban, the study’s first author. “The study data provide the foundational evidence that the method is viable.”

This isn’t the first disease for which Kohn’s team has made significant strides in gene therapy to cure blood disorders. Just last year, the team announced a promising clinical trial to cure Severe Combined Immunodeficiency Syndrome, also known as SCID or “Bubble Baby Disease,” by correcting the genetic mutation that causes it.

While this current study still requires more research before moving into clinical trials, Kohn and his team announced last month that their other gene therapy method, also funded by CIRM, has been approved to start clinical trials. Kohn argues that it’s vital to explore all promising treatment options for this devastating condition:

“Finding varied ways to conduct stem cell gene therapies is important because not every treatment will work for every patient. Both methods could end up being viable approaches to providing one-time, lasting treatments for sickle cell disease and could also be applied to the treatment of a large number of other genetic diseases.”

Find Out More:
Read first-hand about Sickle Cell Disease in our Stories of Hope series.
Watch Donald Kohn speak to CIRM’s governing Board about his research.