New Video: Defeating Sickle Cell Disease with Stem Cells + Gene Therapy

Suffering with an incurable illness is no laughing matter. But last year when we debuted the pilot episode of Stem Cells in Your Face, a lighthearted video series that describes specific diseases and explains the latest progress in stem cell-based therapies, we hoped that a mix of science and humor would help make the information stick in the minds of our viewers. We were thrilled, based on your comments, that you enjoyed watching Treating ALS with a Disease in a Dish as much as we enjoyed producing it and that you wanted to see more:

“Very informative yet easy to understand pilot episode! Hope to see more in this series soon!”

“Might I suggest highlighting a different disease CIRM focuses on in each video?”

Ask and you shall receive. This week we’ve posted the second installment: Defeating Sickle Cell Disease with Stem Cells + Jean Gene Therapy which is being rolled out as a companion piece to our new blog feature series, Genes + Cells.

The video highlights a CIRM-funded clinical trial at UCLA that is testing a stem cell and gene therapy treatment for sickle cell disease. This awful genetic disorder causes red blood cells to assume a sickle shape, clogging blood vessels and producing episodes of excruciating pain, called crises, and leading to progressive organ damage. By twenty years of age about 15 percent of people with sickle cell disease have had major strokes and by 40 almost half of the patients have significant mental dysfunction. The disease strikes one in 500 African Americans and 1 in 36,000 Hispanic people.

A standard treatment for sickle cell disease is a blood transfusion but the benefits are short-lived and require repeated procedures. Bone marrow transplants can be curative but they require a well-matched blood donor which is hard to find and can still be very risky. The UCLA team, on the other hand, aims to correct the sickle cell genetic mutation within the blood stem cells of the patient, which in theory could provide a life-long supply of normal shaped red blood cells. Don Kohn, the lead scientist on the team, explains their strategy in the video:

“The approach that we’re looking at would be to take the patient’s own bone marrow, isolate the [blood] stem cells, in the laboratory put in the gene we’ve been working on that prevents the red blood cells from sickling. So transplanting their own bone marrow back to them in theory should be safe, we don’t have to worry about rejection.“

If all goes well, sickle cell disease may soon be a thing of the past. As patient advocate Adrienne Shapiro has so eloquently stated in a previous Stories of Hope blog post:

“It’s my true belief that I’m going to be the last woman in my family to have a child with sickle cell disease. My afflicted daughter is going to be the last child to suffer, and my other daughter [who does not have the disease but carries the sickle cell mutation] is going to be the last one to fear [passing on the disease to her children]. Stem cells are going to fix this for us and many other families.”

This clinical trial represents one of the first trials to be part of CIRM’s Alpha Stem Cell Network. To learn more, visit our Alpha Clinic webpage. And for more details about CIRM-funding of sickle cell disease research visit these pages:

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.

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.

Scientists Send Rodents to Space; Test New Therapy to Prevent Bone Loss

In just a few months, 40 very special rodents will embark upon the journey of a lifetime.

shutterstock_200932226

Today UCLA scientists are announcing the start of a project that will test a new therapy that has the potential to slow, halt or even reverse bone loss due to disease or injury.

With grant funding from the Center for the Advancement of Science in Space (CASIS), a team of stem cell scientists led by UCLA professor of orthopedic surgery Chia Soo will send 40 rodents to the International Space Station (ISS). Living under microgravity conditions for two months, these rodents will begin to undergo bone loss—thus closely mimicking the conditions of bone loss, known as osteoporosis, seen in humans back on Earth.

At that point, the rodents will be injected with a molecule called NELL-1. Discovered by Soo’s UCLA colleague Kang Ting, this molecule has been shown in early tests to spur bone growth. In this new set of experiments on the ISS, the researchers hope to test the ability of NELL-1 to spur bone growth in the rodents.

The team is optimistic that NELL-1 could really be key to transforming how doctors treat bone loss. Said Ting in a news release:

“NELL-1 holds tremendous hope, not only for preventing bone loss but one day even restoring healthy bone. For patients who are bed-bound and suffering from bone loss, it could be life-changing.”

“Besides testing the limits of NELL-1’s robust bone-producing efforts, this mission will provide new insights about bone biology and could uncover important clues for curing diseases such as osteoporosis,” added Ben Wu, a UCLA bioengineer responsible for initially modifying NELL-1 to make it useful for treating bone loss.

The UCLA team will oversee ground operations while the experiments will be performed by NASA scientists on the ISS and coordinated by CASIS.

These experiments are important not only for developing new therapies to treat gradual bone loss, such as osteoporosis, which normally affects the elderly, but also those who have bone loss due to trauma or injury—including bone loss due to extended microgravity conditions, a persistent problem for astronauts living on the ISS. Said Soo:

“This research has enormous translational application for astronauts in space flight and for patients on Earth who have osteoporosis or other bone-loss problems from disease, illness or trauma.”

CIRM-funded scientists track the steps that take an adult cell back in time

The ability to transform an adult cell back into a stem cell has been heralded as one of the greatest achievements of the 21st century. Scientists have lauded this discovery, made by Nobel Prize-winning scientist Shinya Yamanaka, as a game changer for the future of medicine.

Despite this extraordinary advance, the method remains inefficient. And even the top experts still don’t quite understand how it works.

But now, a team of stem cell scientists from the University of California, Los Angeles (UCLA) has mapped the precise series of steps that an adult skin cell must go through to become a stem cell. The results, published online in the journal Cell, represent a much-needed step towards bringing cellular reprogramming forward.

A colony of iPSC's obtained by reprogramming a specialized cell for two weeks. The starting specialized cells can only make more of themselves, while the reprogrammed cells obtained from them can give rise to all cells of the body.

A colony of iPSC’s obtained by reprogramming a specialized cell for two weeks. The starting specialized cells can only make more of themselves, while the reprogrammed cells obtained from them can give rise to all cells of the body.

In this study, co-first authors Vincent Pasque and Jason Tchieu initiated the reprogramming process, whereby adult cells are reprogrammed back into embryonic-like stem cells. Yamanaka called these cells induced pluripotent stem cells, or iPSCs.

In order to map the steps being taken to reprogram these cells, the team devised a detailed time-course analysis whereby they would observe and analyze the cells each day as they transformed over a period of two weeks.

Importantly, the team found that no matter what type of adult cells were involved, the specific steps it took during reprogramming were the same. This revelation, that all adult cell types follow the same road map, is one of the most exciting discoveries. Said Pasque in a news release:

“The exact stage of reprogramming of any cell can now be determined. This study signals a big change in our thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner.”

The research team, led by CIRM grantee Katherin Plath, also uncovered some interesting information about the sequence of steps taken by these reprogrammed cells.

When an adult cell is reprogrammed back into an iPSC, it is not simply that all the steps that normally take an embryonic stem cell into an adult cell are reversed. Some may be reversed in the correct order, but others are not. And some steps are put off until the very end—indicating strong resistance against reprogramming.

“This reflects how cells do not like to change from one specialized cell type into another and resist a change in cellular identity,” said Pasque.

With future work, the team hopes to continue to investigate the reprogramming process. They are also hopeful that this newfound insight will bring robust iPSC-based therapies to the clinic.

A look at 2014: some of the lowlights of stem cell research this past year

It’s been quite a year in stem cell research. Here at the stem cell agency eight projects that we are funding have been approved for clinical trials and several more hope to get approval in early 2015. And Dr. Don Kohn and his team at UCLA announced that they have effectively cured Severe Combined Immunodeficiency or SCID  a fatal disease that leaves infants with no immune system.

But the news hasn’t been all good. A number of high profile retractions of studies published in prestigious journals have drawn attention to some of the less lovely aspects of science. There are many reasons why a researcher or scientific journal decides to retract a study – falsified data, inability of others to reproduce the findings etc. – but the end result is always the same, a stain on the reputation of science in general.

Of course the only thing worse than a retraction is bad science that is not retracted. That’s why websites such as Retraction Watch are so important. They keep an eye on the field and help draw attention to questionable papers (in all areas of science, not just stem cell research).

Ivan Oransky of Retraction Watch

Ivan Oransky of Retraction Watch

The two founders of the site, Evan Marcus and Ivan Oransky, do a remarkable job of highlighting work that doesn’t stand up to closer scrutiny. This year they worked with the magazine Science to highlight The Top 10 Retractions of 2014.  Sadly, two of the top 10 – including the number one story of the year – concern stem cell research.

The list is a reminder, as we look forward to 2015 for more progress in the field, that we need to always check the credibility of studies or sources we are using. Sometimes something that seems too good to be true, is too good to be true.

Tomorrow, we’ll take a look at the flip side of this discussion, the “Biggest Scientific Breakthroughs of 2014”. It’s always good to end the year on a positive note.

Taking stock: ten years of the stem cell agency, progress and promise for the future

Under some circumstances ten years can seem like a lifetime. But when lives are at stake, ten years can fly by in a flash.

Ten years ago the people of California created the stem cell agency when they overwhelmingly approved Proposition 71, giving us $3 billion to fund and support stem cell research in the state.

In 2004 stem cell science held enormous potential but the field was still quite young. Back then the biology of the cells was not well understood, and our ability to convert stem cells into other cell types for potential therapies was limited. Today, less than 8 years after we actually started funding research, we have ten projects that are expected to be approved for clinical trials by the end of the year, including work in heart disease and cancer, HIV/AIDS and diabetes. So clearly great progress has been made.

Dean Carmen Puliafito and the panel at the Tenth Anniversary event at USC

Dean Carmen Puliafito and the panel at the Tenth Anniversary event at USC

Yesterday we held an event at the University of Southern California (USC) to mark those ten years, to chart where we have come from, and to look to where we are going. It was a gathering of all those who have, as they say, skin in the game: researchers, patients and patient advocates.

The event was held at the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research. As Dr. Carmen Puliafito, Dean of USC’s Keck School of Medicine noted, without CIRM the building would not even exist.

“With this funding, our researchers, and researchers in 11 other facilities throughout the state, gained a dedicated space to hunt for cures for some of the most pernicious diseases in the world, including heart disease, stroke, cancer, diabetes, Alzheimer’s and Parkinson’s disease.”

Dr. Dhruv Sareen from Cedars-Sinai praised CIRM for creating a whole new industry in the state:

“What Silicon Valley has done for technology, CIRM is doing for stem cell research in California.”

One of the beneficiaries of that new industry has been ViaCyte, a San Diego-based company that is now in clinical trials with a small implantable device containing stem cell-derived cells to treat type 1 diabetes. ViaCyte’s Dr. Eugene Brandon said without CIRM none of that would have been possible.

“In 2008 it was extremely hard for a small biotech company to get funding for the kind of work we were doing. Without that support, without that funding from CIRM, I don’t know where this work would be today.”

As with everything we do, at the heart of it are the patients. Fred Lesikar says when he had a massive heart attack and woke up in the hospital his nurse told him about a measure they use to determine the scale of the attack. When he asked how big his attack had been, she replied, “I’ve never seen numbers that large before. Ever.”

Fred told of leaving the hospital a diminished person, unable to do most basic things because his heart had been so badly damaged. But after getting a stem cell-based therapy using his own heart cells he is now as active as ever, something he says doesn’t just affect him.

“It’s not just patients who benefit from these treatments, families do too. It changes the life of the patient, and the lives of all those around them. I feel like I’m back to normal and I’m so grateful for CIRM and Cedars-Sinai for helping me get here.”

The team behind that approach, based at Cedars-Sinai, is now in a much larger clinical trial and we are funding it.

The last word in the event was left to Bob Klein, who led the drive to get Proposition 71 passed and who was the agency’s first Chair. He said looking at what has happened in the last ten years: “it is beyond what I could have imagined.”

Bob noted that the field has not been without its challenges and problems to overcome, and that more challenges and problems almost certainly lie in the future:

“But the genius of the people of this state is reflected in their commitment to this cause, and we should all be eternally grateful for their vision in supporting research that will save and transform people’s lives.”

UCLA team cures infants of often-fatal “bubble baby” disease by inserting gene in their stem cells; sickle cell disease is next target

Poopy diapers, ear-splitting cries, and sleepless nights: sure, the first few weeks of parenthood are grueling but those other moments of cuddling and kissing your little baby are pure bliss.

The bubble boy.  Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

The bubble boy. Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

That wasn’t the case for Alysia and Christian Padilla-Vacarro of Corona, California. Close contact with their infant daughter Evangelina, born in 2012, was off limits. She was diagnosed with a genetic disease that left her with no immune system and no ability to fight off infections so even a minor cold could kill her.

Evangelina was born with Severe Combined Immunodeficiency (SCID) also called “bubble baby” disease, a term coined in the 1970s when the only way to manage the disease was isolating the child in a super clean environment to avoid exposure to germs. Bone marrow transplants from a matched sibling offer a cure but many kids don’t have a match, which makes a transplant very risky. Sadly, many SCID infants die within the first year of life.

Until now, that is.

Today, a UCLA research team led by Donald Kohn, M.D., announced a stunning breakthrough cure that saved Evangelina’s life and all 18 children who have so far participated in the clinical trial. Kohn—the director of UCLA’s Human Gene Medicine Program—described the treatment strategy in a video interview with CIRM (watch the video below):

“We collect some of the baby’s own bone marrow, isolate the [blood] stem cells, add the gene that they’re missing that their immune system needs and then transplant the cells back to them. “

Inserting the missing gene, called ADA, into the blood stem cells restores the cells’ ability to produce a healthy immune system. And since the cells originally came from the infant, there’s no worry about the possible life-threatening complications from receiving non-matched donor cells.

This breakthrough didn’t occur overnight. Kohn and colleagues have been plugging away for over twenty years carrying out trials, observing their limitations and going back to lab to improve the technology. Their dedication has paid off. As Kohn states in a press release:

“All of the children with SCID that I have treated in these stem cell clinical trials would have died in a year or less without this gene therapy, instead they are all thriving with fully functioning immune systems.”

Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life. [Credit: UCLA Broad Center of Regenerative Medicine and Stem Cell Research.]

Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life. [Credit: UCLA Broad Center of Regenerative Medicine and Stem Cell Research.]

For the Padilla-Vacarro family, the dark days after Evangelina’s grave diagnosis have given way to a bright future. Alysia, Evangelina’s mom, poignantly recalled her daughter’s initial recovery:

”It was only around six weeks after the procedure when Dr. Kohn told us Evangelina can finally be taken outside. To finally kiss your child on the lips, to hold her, it’s impossible to describe what a gift that is. I gave birth to my daughter, but Dr. Kohn gave my baby life.”

The team’s next step is to get approval by the Food and Drug Administration (FDA) to provide this treatment to all SCID infants missing the ADA gene.

At the same time, Kohn and colleagues are adapting this treatment approach to cure sickle cell disease, a genetic disease that leads to sickle shaped red blood cells. These misshapen cells are prone to clumping causing debilitating pain, risk of stroke, organ damage and a shortened life span. CIRM is providing over $13 million in funding to support the UCLA team’s clinical trial set to start early next year.

For more information about CIRM-funded sickle cell disease research, visit our fact sheet.

Stem Cell Stories that Caught our Eye: What’s the Best Way to Treat Deadly Cancer, Destroying Red Blood Cells’ Barricade, Profile of CIRM Scientist Denis Evseenko

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 vs. Drugs for Treating Deadly Cancer. When dealing with a potentially deadly form of cancer, choosing the right treatment is critical. But what if that treatment also poses risks, especially for older patients? Could advances in drug development render risky treatments, such as transplants, obsolete?

That was the focus of a pair of studies published this week in the New England Journal of Medicine, where a joint Israeli-Italian research team investigated the comparative benefits of two different treatments for a form of cancer called multiple myeloma.

Multiple myeloma attacks the body’s white blood cells. While rare, it is one of the most deadly forms of cancer—more than half of those diagnosed with the disease do not survive five years after being diagnosed. The standard form of treatment is usually a stem cell transplant, but with newer and better drugs coming on the market, could they render transplants unnecessary?

In the twin studies, the research team divided multiple myeloma patients into two groups. One received a combination of stem cell transplant and chemotherapy, while the other received a combination of drugs including melphalan, prednisone and lenalidmomide. After tracking these patients over a period of four years, the research team saw a clear advantage for those patients that had received the transplant-chemotherapy treatment combination.

To read more about these twin studies check out recent coverage in NewsMaxHealth.

Breaking Blood Cells’ Barricade. The process whereby stem cells mature into red blood cells is, unfortunately, not as fast as scientists would like. In fact, there is a naturally occurring barrier that keeps the production relatively slow. In a healthy person this is not necessarily a problem, but for someone in desperate need of red blood cells—it can prove to be very dangerous.

Luckily, scientists at the University of Wisconsin-Madison have found a way to break through this barrier by switching off two key proteins. Once firmly in the ‘off’ position, the team could boost the production of red blood cells.

These findings, published in the journal Blood, are critical in the context of disease anemia, where the patient’s red blood cell count is low. They also may lead to easier methods of stocking blood banks.

Read more about this exciting discovery at HealthCanal.

CIRM Scientist on the Front Lines of Cancer. Finally, HealthCanal has an enlightening profile of Dr. Denis Evseenko, a stem cell scientist and CIRM grantee from the University of California, Los Angeles (UCLA).

Born in Russia, the profile highlights Evseenko’s passion for studying embryonic stem cells—and their potential for curing currently incurable diseases. As he explains in the article:

“I had a noble vision to develop progressive therapies for the patient. It was a very practical vision too, because I realized how limited therapeutic opportunities could be for the basic scientist, and I had seen many great potential discoveries die out before they ever reached the clinic. Could I help to create the bridge between stem cells, research and actual therapeutics?”

Upon arriving at UCLA, Evseenko knew he wanted to focus this passion into the study of degenerative diseases and diseases related to aging, such as cancer. His bold vision of bridging the gap between basic and translational research has earned him support not only from CIRM, but also the National Institutes of Health and the US Department of Defense, among others. Says Evseenko:

“It’s my hope that we can translate the research we do and discoveries we make here to the clinic to directly impact patient care.”

Building a Blueprint for the Human Brain

How does a brain blossom from a small cluster of cells into nature’s most powerful supercomputer? The answer has long puzzled scientists, but with new advances in stem cell biology, researchers are quickly mapping the complex suite of connections that together make up the brain.

UCLA scientists have developed a new system that can map the development of brain cells.

UCLA scientists have developed a new system that can map the development of brain cells.

One of the latest breakthroughs comes from Dr. Daniel Geschwind and his team at the University of California, Los Angeles (UCLA), who have found a way to track precisely how early-stage brain cells are formed. These findings, published recently in the journal Neuron, shed important light on what had long been considered one of biology’s black boxes—how a brain becomes a brain.

Along with co-lead authors and UCLA postdoctoral fellows Drs. Luis de la Torre-Ubieta and Jason Stein, Geschwind developed a new system that measures key data points along the lifetime of a cell, as it matures from an embryonic stem cell into a functioning brain cell, or neuron. These new data points, such as when certain genes are switched on and off, then allow the team to map how the developing human fetus constructs a functioning brain.

Geschwind is particularly excited about how this new information can help inform how complex neurological conditions—such as autism—can develop. As he stated in a news release:

“These new techniques offer extraordinary promise in the study of autism, because we now have an unbiased and genome-wide view of how genes are used in the development of the disease, like a fingerprint. Our goal is to develop new treatments for autism, and this discovery can provide the basis for improved high-efficiency screening methods and open up an enormous new realm of therapeutic possibilities that didn’t exist before.”

This research, which was funded in part by a training grant from CIRM, stands to improve the way that scientists model disease in a dish—one of the most useful applications of stem cell biology. To that end, the research team has developed a program called CoNTEXT that can identify the maturity levels of cells in a dish. They’ve made this program freely available to researchers, in the hopes that others can benefit. Said de la Torre-Ubieta:

“Our hope is that the scientific community will be able to use this particular program to create the best protocols and refine their methods.”

Want to learn more about how stem cell scientists study disease in a dish? Check out our pilot episode of “Stem Cells in your Face.”