CIRM Board Approves $19.7 Million in Awards for Translational Research Program

In addition to approving funding for breast cancer related brain metastases last week, the CIRM Board also approved an additional $19.7 million geared towards our translational research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.

Before getting into the details of each project, here is a table with a brief synopsis of the awards:

TRAN1 – 11532

Illustration of a healthy eye vs eye with AMD

$3.73 million was awarded to Dr. Mark Humayun at USC to develop a novel therapeutic product capable of slowing the progression of age-related macular degeneration (AMD).

AMD is an eye disease that causes severe vision impairment, resulting in the inability to read, drive, recognize faces, and blindness if left untreated.  It is the leading cause of vision loss in the U.S. and currently affects over 2 million Americans.  By the year 2050, it is projected that the number of affected individuals will more than double to over 5 million.  A layer of cells in the back of the eye called the retinal pigment epithelium (RPE) provide support to photoreceptors (PRs), specialized cells that play an important role in our ability to process images.  The dysfunction and/or loss of RPE cells plays a critical role in the loss of PRs and hence the vision problems observed in AMD.  One form of AMD is known as dry AMD (dAMD) and accounts for about 90% of all AMD cases.

The approach that Dr. Humayun is developing will use a biologic product produced by human embryonic stem cells (hESCs). This material will be injected into the eye of patients with early development of dAMD, supporting the survival of photoreceptors in the affected retina.

TRAN1 – 11579

Illustration depicting the role neuronal relays play in muscle sensation

$6.23 million was awarded to Dr. Mark Tuszynski at UCSD to develop a neural stem cell therapy for spinal cord injury (SCI).

According to data from the National Spinal Cord Injury Statistical Center, as of 2018, SCI affects an estimated 288,000 people in the United States alone, with about 17,700 new cases each year. There are currently no effective therapies for SCI. Many people suffer SCI in early adulthood, leading to life-long disability and suffering, extensive treatment needs and extremely high lifetime costs of health care.

The approach that Dr. Tuszynski is developing will use hESCs to create neural stem cells (NSCs).  These newly created NSCs would then be grafted at the site of injury of those with SCI.  In preclinical studies, the NSCs have been shown to support the formation of neuronal relays at the site of SCI.  The neuronal relays allow the sensory neurons in the brain to communicate with the motor neurons in the spinal cord to re-establish muscle control and movement.

TRAN1 – 11548

Graphic depicting the challenges of traumatic brain injury (TBI)

$4.83 million was awarded to Dr. Brian Cummings at UC Irvine to develop a neural stem cell therapy for traumatic brain injury (TBI).

TBI is caused by a bump, blow, or jolt to the head that disrupts the normal function of the brain, resulting in emotional, mental, movement, and memory problems. There are 1.7 million people in the United States experiencing a TBI that leads to hospitalization each year. Since there are no effective treatments, TBI is one of the most critical unmet medical needs based on the total number of those affected and on a cost basis.

The approach that Dr. Cummings is developing will also use hESCs to create NSCs.  These newly created NSCs would be integrated with injured tissue in patients and have the ability to turn into the three main cell types in the brain; neurons, astrocytes, and oligodendrocytes.  This would allow for TBI patients to potentially see improvements in issues related to memory, movement, and anxiety, increasing independence and lessening patient care needs.

TRAN1 – 11628

Illustration depicting the brain damage that occurs under hypoxic-ischemic conditions

$4.96 million was awarded to Dr. Evan Snyder at Sanford Burnham Prebys to develop a neural stem cell therapy for perinatal hypoxic-ischemic brain injury (HII).

HII occurs when there is a lack of oxygen flow to the brain.  A newborn infant’s body can compensate for brief periods of depleted oxygen, but if this lasts too long, brain tissue is destroyed, which can cause many issues such as developmental delay and motor impairment.  Current treatment for this condition is whole-body hypothermia (HT), which consists of significantly reducing body temperature to interrupt brain injury.  However, this is not very effective in severe cases of HII. 

The approach that Dr. Snyder is developing will use an established neural stem cell (NSC) line.   These NSCs would be injected and potentially used alongside HT treatment to increase protection from brain injury.

Stories that caught our eye: SanBio’s Traumatic Brain Injury trial hits its target; A new approach to endometriosis; and a SCID kid celebrates Halloween in style

TBI

Traumatic brain injury: graphic courtesy Brainline.org

Hopeful signs for treating brain injuries

There are more than 200,000 cases of traumatic brain injury (TBI) in the US every year. The injuries can be devastating, resulting in everything from difficult sleeping to memory loss, depression and severe disability. There is no cure. But this week the SanBio Group had some encouraging news from its Phase 2 STEMTRA clinical trial.

In the trial patients with TBI were given stem cells, derived from the bone marrow of healthy adult donors. When transplanted into the area of injury in the brain, these cells appear to promote recovery by stimulating the brain’s own regenerative ability.

In this trial the cells demonstrated what the company describes as “a statistically significant improvement in their motor function compared to the control group.”

CIRM did not fund this research but we are partnering with SanBio on another clinical trial targeting stroke.

 

Using a woman’s own cells to heal endometriosis

Endometriosis is an often painful condition that is caused when the cells that normally line the inside of the uterus grow outside of it, causing scarring and damaging other tissues. Over time it can result in severe pain, infertility and increase a woman’s risk for ovarian cancer.

There is no effective long-term treatment but now researchers at Northwestern Medicine have developed an approach, using the woman’s own cells, that could help treat the problem.

The researchers took cells from women, turned them into iPS pluripotent stem cells and then converted those into healthy uterine cells. In laboratory tests these cells responded to the progesterone, the hormone that plays a critical role in the uterus.

In a news release, Dr. Serdar Bulun, a senior author of the study, says this opens the way to testing these cells in women:

“This is huge. We’ve opened the door to treating endometriosis. These women with endometriosis start suffering from the disease at a very early age, so we end up seeing young high school girls getting addicted to opioids, which totally destroys their academic potential and social lives.”

The study is published in the journal Stem Cell Reports.

IMG_20181031_185752

Happy Halloween from a scary SCID kid

A lot of the research we write about on the Stem Cellar focuses on potential treatments or new approaches that show promise. So every once in a while, it’s good to remind ourselves that there are already stem cell treatments that are not just showing promise, they are saving lives.

That is the case with Ja’Ceon Golden. Regular readers of our blog know that Ja’Ceon was diagnosed with Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease” when he was just a few months old. Children born with SCID often die in the first few years of life because they don’t have a functioning immune system and so even a simple infection can prove life-threatening.

Fortunately Ja’Ceon was enrolled in a CIRM-funded clinical trial at UC San Francisco where his own blood stem cells were genetically modified to correct the problem.

IMG_20181030_123500

Today he is a healthy, happy, thriving young boy. These pictures, taken by his great aunt Dannie Hawkins, including one of him in his Halloween costume, show how quickly he is growing. And all thanks to some amazing researchers, an aunt who wouldn’t give up on him, and the support of CIRM.

Blocking spike in stem cell growth after brain injury may lessen memory decline, seizures

Survivors of traumatic brain injury (TBI) often suffer from debilitating, life changing symptoms like memory decline and epileptic seizures. Researchers had observed that following TBI, a stem cell-rich area of the brain provides a spike in new nerve cell growth, presumably to help replace damaged or destroyed brain cells. But, like a lot of things in biology, more is not always better. And a new report in Stem Cell Reports provides evidence that this spark of brain cell growth shortly after TBI may actually be responsible for post-injury seizures as well as long-term memory problems for people with this condition.The Rutgers University research team behind the study came to this counterintuitive conclusion by examining brain injury in laboratory rats. They showed that brain cells at the injury site that are known to play a role in memory had doubled in number within three days after injury. But a month later, these brain cells had decreased by more than half the amount seen in rats without injury. Neural stem cells, which develop into the mature cells found in the brain, showed this same up and down pattern, suggesting they were responsible for the loss of the brain cells. Lead scientist, professor Viji Santhakumar, described how these changes in brain cell growth lead to brain injury symptoms:

“There is an initial increase in birth of new neurons after a brain injury but within weeks, there is a dramatic decrease in the normal rate at which neurons are born, depleting brain cells that under normal circumstances should be there to replace damaged cells and repair the brain’s network,” she said in a press release. “The excess new neurons lead to epileptic seizures and could contribute to cognitive decline. It is normal for the birth of new neurons to decline as we age. But what we found in our study was that after a head injury the decline seems to be more rapid.”

The researchers next aimed to slow down this increase in nerve cell growth after injury. To accomplish this goal, they used an anti-cancer drug currently in clinical trials which has been known to block the growth and survival of new nerve cells. Sure enough, the drug blocked this initial, rapid burst in nerve cells in the rats, which prevented the long-term decline in the brain cells that are involved in memory decline. The team also reported that the rats were less vulnerable to seizures when this drug was administered.

“That’s why we believe that limiting this process might be beneficial to stopping seizures after brain injury,” Dr. Santhakumar commented.

Hopefully, these findings will one day help lessen these short- and long-term, life-altering symptoms seen after brain injury.

Stem cell stories that caught our eye: Amy Schumer’s MS fundraising; healing traumatic brain injury; schizophrenia iPS insights

Amy Schumer and Paul Shaffer raise money for MS. (Karen Ring)
Two famous individuals, one a comedian/movie star, the other a well-known musician, have combined forces to raise money for an important cause. Amy Schumer and Paul Shaffer have pledged to raise $2.5 million dollars to help support research into multiple sclerosis (MS). This disease affects the nerve cells in both the brain and spinal cord. It eats away at the protective myelin sheaths that coat and protect nerve cells and allow them to relay signals between the brain and the rest of the body. As a result, patients experience a wide range of symptoms including physical, mental and psychiatric problems.

1507_schumer1

Comedian Amy Schumer and her Dad who has MS.
(National MS Society)

The jury is still out on the exact cause of MS and there is no cure available. But the Tisch MS Research Center of New York is trying to change that. It is “dedicated to finding the cause and cure for MS” and recently announced, at its annual Future Without MS Gala, that it has pledged to raise $10 million to fund the stem cell research efforts ongoing at the Center. Currently, Tisch is “the only center with an FDA approved stem cell clinical trial for MS in the United States.” You can read more about this clinical trial, which is transplanting mesenchymal stem cell-derived brain progenitor cells into the spinal cord, on the Tisch website.

At the gala, both Amy Schumer and Paul Shaffer were present to show their support for MS research. In an interview with People magazine, Amy revealed that her father struggles with MS. She explained, “Some days he’s really good and he’s with it and we’re joking around. And some days I go to visit my dad and it’s so painful. I can’t believe it.” Her experience watching her dad battle with MS inspired her to write and star in the movie TRAINWRECK, and also to get involved in supporting MS research. “If I can help at all I’m gonna try, even if that means I’ll get hurt,” she said.

Stem cells may help traumatic brain injuries (Kevin McCormack
Traumatic brain injury (TBI) is a huge problem in the US. According to the Centers for Disease Control and Prevention around 1.7 million Americans suffer a TBI every year; 250,000 of those are serious enough to result in a hospitalization; 52,000 are fatal. Even those who survive a TBI are often left with permanent disabilities, caused by swelling in the brain that destroys brain cells.

Now researchers at the University of Texas Health Science Center at Houston say using a person’s own stem cells could help reduce the severity of a TBI.

The study, published in the journal Stem Cells, found that taking stem cells from a person’s own bone marrow and then re-infusing them into the bloodstream, within 48 hours of the injury, can help reduce the swelling and inflammation that damages the brain.

In an interview with the Houston Chronicle Charles Cox, the lead researcher – and a member of CIRM’s Grants Working Group panel of experts – says the results are not a cure but they are encouraging:

charlescox

Charles Cox
(Drew Donovan / UTHealth)

“I’m talking about the difference between someone who recovers to the point that they can take care of themselves, and someone who is totally dependent on someone else for even simple tasks, like using the bathroom and bathing. That’s a dramatic difference.”

Schizophrenia: an imbalance of brain cell types?

Schizophrenia is a chronic mental disorder with a wide range of disabling symptoms such as delusional thoughts, hearing voices, anxiety and an inability to experience pleasure. It’s estimated that half of those with schizophrenia abuse drugs and alcohol, which likely contributes to increased incidence of unemployment, homelessness and suicide. No cure exists for the disorder because scientists don’t fully understand what causes it, and available treatments only mask the symptoms.

schizophrenia_art

A patient’s artistic representation of living with schizophrenia
(Wikipedia)

This week, researchers at the RIKEN Brain Science Institute in Japan reported new clues about what goes wrong at a cellular and molecular level in the brains of people with schizophrenia. The scientists created induced pluripotent stem cells (iPSCs) from healthy donors, as well as patients with schizophrenia, and then changed or specialized them into nerve cells, or neurons. They found that fewer iPSCs developed into neurons when comparing the cells from people with schizophrenia to the healthy donor cells. Instead, more iPSCs specialized into astrocytes, another type of brain cell. This fewer neurons/more astrocytes shift was also seen in brains of deceased donors who had schizophrenia.

Looking inside the cells, the researchers found higher levels of a protein called p38 in the neurons derived from the people with schizophrenia. Inhibiting the activity of p38 led to increased number of neurons and fewer astrocytes, which resembles the healthy state. These results, published in Translational Psychiatry and picked up by Health Canal, point to inhibitors of p38 activity as a potential path for developing new treatments.