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.”

 


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Avalanches of exciting new stem cell research at the Keystone Symposia near Lake Tahoe

From January 8th to 13th, nearly 300 scientists and trainees from around the world ascended the mountains near Lake Tahoe to attend the joint Keystone Symposia on Neurogenesis and Stem Cells at the Resort at Squaw Creek. With record-high snowfall in the area (almost five feet!), attendees had to stay inside to stay warm and dry, and even when we lost power on the third day on the mountain there was no shortage of great science to keep us entertained.

Boy did it snow at the Keystone Conference in Tahoe!

Boy did it snow at the Keystone Conference in Tahoe!

One of the great sessions at the meeting was a workshop chaired by CIRM’s Senior Science Officer, Dr. Kent Fitzgerald, called, “Bridging and Understanding of Basic Science to Enable/Predict Clinical Outcome.” This workshop featured updates from the scientists in charge of three labs currently conducting clinical trials funded and supported by CIRM.

Regenerating injured connections in the spinal cord with neural stem cells

Mark Tuszynski, UCSD

Mark Tuszynski, UCSD

The first was a stunning talk by Dr. Mark from UCSD who is investigating how neural stem cells can help outcomes for those with spinal cord injury. The spinal cord contains nerves that connect your brain to the rest of your body so you can sense and move around in your environment, but in cases of severe injury, these connections are cut and the signal is lost. The most severe of these injuries is a complete transection, which is when all connections have been cut at a given spot, meaning no signal can pass through, just like how no cars could get through if a section of the Golden Gate Bridge was missing. His lab works in animal models of complete spinal cord transections since it is the most challenging to repair.

As Dr. Tuszynski put it, “the adult central nervous system does not spontaneously regenerate [after injury], which is surprising given that it does have its own set of stem cells present throughout.” Their approach to tackle this problem is to put in new stem cells with special growth factors and supportive components to let this process occur.

Just as most patients wouldn’t be able to come in for treatment right away after injury, they don’t start their tests until two weeks after the injury. After that, they inject neural stem cells from either the mouse, rat, or human spinal cord at the injury site and then wait a bit to see if any new connections form. Their group has shown very dramatic increases in both the number of new connections that regenerate from the injury site and extend much further than previous efforts have shown. These connections conduct electrochemical messages as normal neurons do, and over a year later they see no functional decline or tumors forming, which is often a concern when transplanting stem cells that normally like to divide a lot.

While very exciting, he cautions, “this research shows a major opportunity in neural repair that deserves proper study and the best clinical chance to succeed”. He says it requires thorough testing in multiple animal models before going into humans to avoid a case where “a clinical trial fails, not because the biology is wrong, but because the methods need tweaking.”

Everyone needs support – even dying cells

The second great talk was by Dr. Clive Svendsen of Cedars-Sinai Regenerative Medicine Institute on how stem cells might help provide healthy support cells to rescue dying neurons in the brains of patients with neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s. Some ALS cases are hereditary and would be candidates for a treatment using gene editing techniques. However, around 90 percent of ALS cases are “sporadic” meaning there is no known genetic cause. Dr. Svendsen explained how in these cases, a stem cell-based approach to at least fix the cellular cause of the disease, would be the best option.

While neurons often capture all the attention in the brain, since they are the cells that actually send messages that underlie our thoughts and behaviors, the Svendsen lab spends a great deal of time thinking about another type of cell that they think will be a powerhouse in the clinic: astrocytes. Astrocytes are often labeled as the support cells of the brain as they are crucial for maintaining a balance of chemicals to keep neurons healthy and functioning. So Dr. Svendsen reasoned that perhaps astrocytes might unlock a new route to treating neurodegenerative diseases where neurons are unhealthy and losing function.

ALS is a devastating disease that starts with early muscle twitches and leads to complete paralysis and death usually within four years, due to the rapid degeneration of motor neurons that are important for movement all over the body. Svendsen’s team found that by getting astrocytes to secrete a special growth factor, called “GDNF”, they could improve the survival of the neurons that normally die in their model of ALS by five to six times.

After testing this out in several animal models, the first FDA-approved trial to test whether astrocytes from fetal tissue can slow spinal motor neuron loss will begin next month! They will be injecting the precursor cells that can make these GDNF-releasing astrocytes into one leg of ALS patients. That way they can compare leg function and track whether the cells and GDNF are enough to slow the disease progression.

Dr. Svendsen shared with us how long it takes to create and test a treatment that is committed to safety and success for its patients. He says,

Clive Svendsen has been on a 15-year quest to develop an ALS therapy

Clive Svendsen 

“We filed in March 2016, submitted the improvements Oct 2016, and we’re starting our first patient in Feb 2017. [One document is over] 4500 pages… to go to the clinic is a lot of work. Without CIRM’s funding and support we wouldn’t have been able to do this. This isn’t easy. But it is doable!”

 

Improving outcomes in long-term stroke patients in unknown ways

Gary Steinberg

Gary Steinberg

The last speaker for the workshop, Dr. Gary Steinberg, a neurosurgeon at Stanford who is looking to change the lives of patients with severe limitations after having a stroke. The deficits seen after a stroke are thought to be caused by the death of neurons around the area where the stroke occurred, such that whatever functions they were involved with is now impaired. Outcomes can vary for stroke patients depending on how long it takes for them to get to the emergency department, and some people think that there might be a sweet spot for when to start rehabilitative treatments — too late and you might never see dramatic recovery.

But Dr. Steinberg has some evidence that might make those people change their mind. He thinks, “these circuits are not irreversibly damaged. We thought they were but they aren’t… we just need to continue figuring out how to resurrect them.”

He showed stunning videos from his Phase 1/2a clinical trial of several patients who had suffered from a stroke years before walking into his clinic. He tested patients before treatment and showed us videos of their difficulty to perform very basic movements like touching their nose or raising their legs. After carefully injecting into the brain some stem cells taken from donors and then modified to boost their ability to repair damage, he saw a dramatic recovery in some patients as quickly as one day later. A patient who couldn’t lift her leg was holding it up for five whole seconds. She could also touch her arm to her nose, whereas before all she could do was wiggle her thumb. One year later she is even walking, albeit slowly.

He shared another case of a 39 year-old patient who suffered a stroke didn’t want to get married because she felt she’d be embarrassed walking down the aisle, not to mention she couldn’t move her arm. After Dr. Steinberg’s trial, she was able to raise her arm above her head and walk more smoothly, and now, four years later, she is married and recently gave birth to a boy.

But while these studies are incredibly promising, especially for any stroke victims, Dr. Steinberg himself still is not sure exactly how this stem cell treatment works, and the dramatic improvements are not always consistent. He will be continuing his clinical trial to try to better understand what is going on in the injured and recovering brain so he can deliver better care to more patients in the future.

The road to safe and effective therapies using stem cells is long but promising

These were just three of many excellent presentations at the conference, and while these talks involved moving science into human patients for clinical trials, the work described truly stands on the shoulders of all the other research shared at conferences, both present and past. In fact, the reason why scientists gather at conferences is to give one another feedback and to learn from each other to better their own work.

Some of the other exciting talks that are surely laying down the framework for future clinical trials involved research on modeling mini-brains in a dish (so-called cerebral organoids). Researchers like Jürgen Knoblich at the Institute of Molecular Biotechnology in Austria talked about the new ways we can engineer these mini-brains to be more consistent and representative of the real brain. We also heard from really fundamental biology studies trying to understand how one type of cell becomes one vs. another type using the model organism C. elegans (a microscopic, transparent worm) by Dr. Oliver Hobert of Columbia University. Dr. Austin Smith, from the University of Cambridge in the UK, shared the latest about the biology of pluripotent cells that can make any cell type, and Stanford’s Dr. Marius Wernig, one of the meeting’s organizers, told us more of what he’s learned about the road to reprogramming an ordinary skin cell directly into a neuron.

Stay up to date with the latest research on stem cells by continuing to follow this blog and if you’re reading this because you’re considering a stem cell treatment, make sure you find out what’s possible and learn about what to ask by checking out closerlookatstemcells.org.


Samantha Yammine

Samantha Yammine

Samantha Yammine is a science communicator and a PhD candidate in Dr. Derek van der Kooy’s lab at the University of Toronto. You can learn more about Sam and her research on her website.

Using stem cells to fix bad behavior in the brain

 

finkbeiner-skibinski-16x9-13

Gladstone Institutes Steven Finkbeiner and Gaia Skibinski: Photo courtesy Chris Goodfellow, Gladstone Institutes

Diseases of the brain have many different names, from Alzheimer’s and Parkinson’s to ALS and Huntington’s, but they often have similar causes. Researchers at the Gladstone Institutes in San Francisco are using that knowledge to try and find an approach that might be effective against all of these diseases. In a new CIRM-funded study, they have identified one protein that could help do just that.

Many neurodegenerative diseases are caused by faulty proteins, which start to pile up and cause damage to neurons, the brain cells that are responsible for processing and transmitting information. Ultimately, the misbehaving proteins cause those cells to die.

The researchers at the Gladstone found a way to counter this destructive process by using a protein called Nrf2. They used neurons from humans (made from induced pluripotent stem cells – iPSCs – hence the stem cell connection here) and rats. They then tested these cells in neurons that were engineered to have two different kinds of mutations found in  Parkinson’s disease (PD) plus the Nrf2 protein.

Using a unique microscope they designed especially for this study, they were able to track those transplanted neurons and monitor what happened to them over the course of a week.

The neurons that expressed Nrf2 were able to render one of those PD-causing proteins harmless, and remove the other two mutant proteins from the brain cells.

In a news release to accompany the study in The Proceedings of the National Academy of Sciences, first author Gaia Skibinski, said Nrf2 acts like a house-cleaner brought in to tidy up a mess:

“Nrf2 coordinates a whole program of gene expression, but we didn’t know how important it was for regulating protein levels until now. Over-expressing Nrf2 in cellular models of Parkinson’s disease resulted in a huge effect. In fact, it protects cells against the disease better than anything else we’ve found.”

Steven Finkbeiner, the senior author on the study and a Gladstone professor, said this model doesn’t just hold out hope for treating Parkinson’s disease but for treating a number of other neurodegenerative problems:

“I am very enthusiastic about this strategy for treating neurodegenerative diseases. We’ve tested Nrf2 in models of Huntington’s disease, Parkinson’s disease, and ALS, and it is the most protective thing we’ve ever found. Based on the magnitude and the breadth of the effect, we really want to understand Nrf2 and its role in protein regulation better.”

The next step is to use this deeper understanding to identify other proteins that interact with Nrf2, and potentially find ways to harness that knowledge for new therapies for neurodegenerative disorders.

Ingenious CIRM-funded stem cell approach to treating ALS gets go-ahead to start clinical trial

svend

Clive Svendsen

Amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease, was first identified way back in 1869 but today, more than 150 years later, there are still no effective treatments for it. Now a project, funded by CIRM, has been given approval by the Food and Drug Administration (FDA) to start a clinical trial that could help change that.

Clive Svendsen and his team at Cedars-Sinai are about to start a clinical trial they hope will help slow down the progression of the disease. And they are doing it in a particularly ingenious way. More on that in a minute.

First, let’s start with ALS itself. It’s a particularly nasty, rapidly progressing disease that destroys motor neurons, those are the nerve cells in the brain and spinal cord that control movement. People with ALS lose the ability to speak, eat, move and finally, breathe. The average life expectancy after diagnosis is just 3 – 4 years. It’s considered an orphan disease because it affects only around 30,000 people in the US; but even with those relatively low numbers that means that every 90 minutes someone in the US is diagnosed with ALS, and every 90 minutes someone in the US dies of ALS.

Ingenious approach

In this clinical trial the patients will serve as their own control group. Previous studies have shown that the rate of deterioration of muscle movement in the legs of a person with ALS is the same for both legs. So Svendsen and his team will inject specially engineered stem cells into a portion of the spine that controls movement on just one side of the body. Neither the patient nor the physician will know which side has received the cells. This enables the researchers to determine if the treated leg is deteriorating at a slower rate than the untreated leg.

The stem cells being injected have been engineered to produce a protein called glial cell line derived neurotrophic factor (GDNF) that helps protect motor neurons. Svendsen and the team hope that by providing extra GDNF they’ll be able to protect the motor neurons and keep them alive.

Reaching a milestone

In a news release announcing the start of the trial, Svendsen admitted ALS is a tough disease to tackle:

“Any time you’re trying to treat an incurable disease, it is a long shot, but we believe the rationale behind our new approach is strong.”

Diane Winokur, the CIRM Board patient advocate for ALS, says this is truly a milestone:

“In the last few years, thanks to new technologies, increased interest, and CIRM support, we finally seem to be seeing some encouraging signs in the research into ALS. Dr. Svendsen has been at the forefront of this effort for the 20 years I have followed his work.  I commend him, Cedars-Sinai, and CIRM.  On behalf of those who have suffered through this cruel disease and their families and caregivers, I am filled with hope.”

You can read more about Clive Svendsen’s long journey to this moment here.

 

How the Ice Bucket Challenge changed the fight against ALS

Ice Bucket2

200 people in Boston take the Ice Bucket Challenge: Photo courtesy Forbes

A couple of years ago millions of people did something they probably never thought they would: they dumped a bucket of ice cold water on their head to raise awareness about a disease most of them had probably never heard of, and almost certainly knew very little about.

The disease was ALS, also known as Lou Gehrig’s disease, and the Ice Bucket Challenge was something that went from a fun idea by a supporter of the ALS Association, to a blockbuster $220 million fundraiser. Like any good idea it sparked a backlash with critics accusing it of being a lazy way for people to feel good without actually doing anything, of diverting money from other charities, and even of just wasting water at a time of drought (at least here in California.)

But two years later we can now look back and see if those critics were correct, and if the money raised did make a difference. And the answer, I’m happy to say, is no and yes. In that order.

An article in the New Yorker magazine, by James Surowiecki, takes a look at what has happened since the Ice Bucket Challenge exploded on the scene and it has some good news:

  • Contributions to the ALS Association remain higher than before the Challenge
  • The average age of donors dropped from 50+ to 35
  • The Challenge may have helped spur an increase in overall donations to charity

All this is, of course, excellent news. But there’s an even more important point, which is that the money raised by the Challenge has helped advance ALS research further and faster than ever before.

Barbara Newhouse, the CEO of the ALS Association told Surowiecki:

“The research environment is dramatically different from what it was. We’re seeing research that’s really moving the needle not just on the causes of the disease but also on treatments and therapies.”

As an example Newhouse cites a study, published in Science  last summer, by researchers at Johns Hopkins that helped explain protein clumps found in the brains of people with ALS. Philip Wong, one of the lead authors of the study, says money raised by the Challenge helped make their work possible;

“Without it, we wouldn’t have been able to come out with the studies as quickly as we did. The funding from the ice bucket is just a component of the whole—in part, it facilitated our effort.”

And just this week the ALS Association said funding from the Challenge helped identify a gene connected to the disease.

Having been one of those who took a dunk for science – and we did ours early on, when the Challenge had only raised $4m – it’s nice to know something as silly and simple can have such a profound impact on developing treatments for a deadly disorder.

 

 

A Dream made me change my mind. Almost.

Dream Alliance

Dream Alliance: photo courtesy Daily Telegraph, UK

On Friday I was faced with the real possibility that a horse had made an ass out of me.

Over the years we have written many articles about the risks of unproven stem cell therapies, treatments that have not yet been shown in clinical trials to be safe and effective. Often we have highlighted the cases of high profile athletes who have undergone stem cell treatments for injuries when there is little evidence that the treatments they are getting work.

Well, on Friday I saw an athlete who bounced back from a potentially career-ending injury to enjoy an amazing career thanks to a stem cell treatment. I wondered if I was going to have to revise my thoughts on this topic. Then my wife pointed out to me that the athlete was a horse.

We had been watching the movie Dark Horse, a truly delightful true story about a group of working class people in a Welsh mining village who bred and raised a horse that went on to great success as a race horse – often beating out thoroughbreds that were worth millions of dollars.

 

At one point the horse, Dream Alliance, suffered an almost fatal injury. Everyone assumed his career was over. But thanks to a stem cell treatment he was able to return to the track and became the first horse to win a major race after undergoing stem cell surgery.

It shouldn’t be too surprising that stem cells can help heal serious injuries in horses, the researchers at UC Davis have been using them to help treat horses for years – with great success. The danger comes in then assuming that just because stem cells work for horses, they’ll work for people. And that if they can cure one kind of injury, why not another.

That thought was driven home to me on Saturday when I was giving a talk to a support group for ALS or Lou Gehrig’s disease. ALS is a nasty, rapidly progressive disease that attacks the motor nerve cells in the brain and spinal cord, destroying a person’s ability to move, eat, speak or breath.

One person asked about a clinic they had been talking to which claimed it might be able to help them. The clinic takes fat from the person with ALS, isolates the stem cells in the fat and injects it back into the person. The clinic claims it’s been very effective in treating injuries such as torn muscles, and that it also works for other problems like Parkinson’s so it might help someone with ALS.

And that’s the problem. We hear about one success story that seems to prove stem cells can do amazing things, and then we are tempted to hope that if it works for one kind of injury, it might work for another, or even for a neurodegenerative disease.

And hope doesn’t come cheap. The cost of the procedure was almost $10,000.

If you have a disease like ALS for which there is no cure, and where the life expectancy is between two to five years, you can understand why someone would be tempted to try anything, no matter how implausible. What is hard is when you have to tell them that without any proof that it works, and little scientific rational as to why it would work, that it’s hard to recommend they try using their own fat cells to treat their ALS.

At CIRM we are investing more than $56.5 million in 21 different projects targeting ALS.   We are hopeful one of them, Clive Svendsen’s research at Cedars-Sinai Medical Center,  will soon get approval from the FDA to start a clinical trial.

Much as we would like to believe in miracles, medical breakthroughs usually only come after years of hard, methodical work. It would be great if injecting your own fat-derived stem cells into your body could cure you of all manner of ailments. But there’s no evidence to suggest it will.

The movie Dark Horse shows that for one horse, for one group of people in a small Welsh mining village, stem cells helped create a happy ending. We are hoping stem cells will one day offer the same sense of hope and possibility for people battling deadly diseases like ALS. But that day is not yet here.

 

 

Rare disease underdogs come out on top at CIRM Board meeting

 

It seems like an oxymoron but one in ten Americans has a rare disease. With more than 7,000 known rare diseases it’s easy to see how each one could affect thousands of individuals and still be considered a rare or orphan condition.

Only 5% of rare diseases have FDA approved therapies

rare disease

(Source: Sermo)

People with rare diseases, and their families, consider themselves the underdogs of the medical world because they often have difficulty getting a proper diagnosis (most physicians have never come across many of these diseases and so don’t know how to identify them), and even when they do get a diagnosis they have limited treatment options, and those options they do have are often very expensive.  It’s no wonder these patients and their families feel isolated and alone.

Rare diseases affect more people than HIV and Cancer combined

Hopefully some will feel less isolated after yesterday’s CIRM Board meeting when several rare diseases were among the big winners, getting funding to tackle conditions such as ALS or Lou Gehrig’s disease, Severe Combined Immunodeficiency or SCID, Canavan disease, Tay-Sachs and Sandhoff disease. These all won awards under our Translation Research Program except for the SCID program which is a pre-clinical stage project.

As CIRM Board Chair Jonathan Thomas said in our news release, these awards have one purpose:

“The goal of our Translation program is to support the most promising stem cell-based projects and to help them accelerate that research out of the lab and into the real world, such as a clinical trial where they can be tested in people. The projects that our Board approved today are a great example of work that takes innovative approaches to developing new therapies for a wide variety of diseases.”

These awards are all for early-stage research projects, ones we hope will be successful and eventually move into clinical trials. One project approved yesterday is already in a clinical trial. Capricor Therapeutics was awarded $3.4 million to complete a combined Phase 1/2 clinical trial treating heart failure associated with Duchenne muscular dystrophy with its cardiosphere stem cell technology.  This same Capricor technology is being used in an ongoing CIRM-funded trial which aims to heal the scarring that occurs after a heart attack.

Duchenne muscular dystrophy (DMD) is a genetic disorder that is marked by progressive muscle degeneration and weakness. The symptoms usually start in early childhood, between ages 3 and 5, and the vast majority of cases are in boys. As the disease progresses it leads to heart failure, which typically leads to death before age 40.

The Capricor clinical trial hopes to treat that aspect of DMD, one that currently has no effective treatment.

As our President and CEO Randy Mills said in our news release:

Randy Mills, Stem Cell Agency President & CEO

Randy Mills, Stem Cell Agency President & CEO

“There can be nothing worse than for a parent to watch their child slowly lose a fight against a deadly disease. Many of the programs we are funding today are focused on helping find treatments for diseases that affect children, often in infancy. Because many of these diseases are rare there are limited treatment options for them, which makes it all the more important for CIRM to focus on targeting these unmet medical needs.”

Speaking on Rare Disease Day (you can read our blog about that here) Massachusetts Senator Karen Spilka said that “Rare diseases impact over 30 Million patients and caregivers in the United States alone.”

Hopefully the steps that the CIRM Board took yesterday will ultimately help ease the struggles of some of those families.

Rare Disease Day, a chance to raise awareness and hope.

logo-rare-disease-day

Battling a deadly disease like cancer or Alzheimer’s is difficult; but battling a rare and deadly disease is doubly so. At least with common diseases there is a lot of research seeking to develop new treatments. With rare diseases there is often very little research, and so there are fewer options for treatment. Even just getting a diagnosis can be hard because most doctors may never have heard about, let alone seen, a case of a disease that only affects a few thousand individuals.

That’s why the last day of February, every year, has been designated Rare Disease Day.  It’s a time to raise awareness amongst the public, researchers, health  professionals and policy makers about the impact these diseases have on the lives of those affected by them. This means not just the individual with the problem, but their family and friends too.

There are nearly 7,000 diseases in the U.S. that are considered rare, meaning they affect fewer than 200,000 people at any given time.

No numbers no money

The reason why so many of these diseases have so few treatment options is obvious. With diseases that affect large numbers of people a new treatment or cure stands to make the company behind it a lot of money. With diseases that affect very small numbers of people the chances of seeing any return on investment are equally small.

Fortunately at CIRM we don’t have to worry about making a profit, all we are concerned with is accelerating stem cell treatments to patients with unmet medical needs. And in the case of people with rare diseases, those needs are almost invariably unmet.

That’s why over the years we have invested heavily in diseases that are often overlooked because they affect relatively small numbers of people. In fact right now we are funding clinical trials in several of these including sickle cell anemia, retinitis pigmentosa and chronic granulomatous disease. We are also funding work in conditions like Huntington’s disease, ALS or Lou Gehrig’s disease, and SCID or “bubble baby” disease.

Focus on the people

As in everything we do our involvement is not just about funding research – important as that is – it’s also about engaging with the people most affected by these diseases, the patient advocate community. Patient advocates help us in several ways:

  • Collaborating with us and other key stakeholders to try and change the way the Food and Drug Administration (FDA) works. Our goal is to create an easier and faster, but no less safe, method of approving the most promising stem cell therapies for clinical trial. With so few available treatments for rare diseases having a smoother route to a clinical trial will benefit these communities.
  • Spreading the word to researchers and companies about CIRM 2.0, our new, faster and more streamlined funding opportunities to help us move the most promising therapies along as fast as possible. The good news is that this means anyone, anywhere can apply for funding. We don’t care how many people are affected by a disease, we only care about the quality of the proposed research project that could help them.
  • Recruiting Patient Advocates to our Clinical Advisory Panels (CAPs), teams that we assign to each project in a clinical trial to help guide and inform the researchers at every stage of their work. This not only gives each project the best possible chance of succeeding but it also helps the team stay focused on the mission, of saving, and changing, people’s lives.
  • Helping us recruit patients for clinical trials. The inability to recruit and retain enough patients to meet a project’s enrollment requirements is one of the biggest reasons many clinical trials fail. This is particularly problematic for rare diseases. By using Patient Advocates to increase our ability to enroll and retain patients we will increase the likelihood a clinical trial is able to succeed.

Organizing to fight back

There are some great organizations supporting and advocating on behalf of families affected by rare diseases, such as the EveryLife Foundation  and the National Organization for Rare Diseases (NORD).  They are working hard to raise awareness about these diseases, to get funding to do research, and to clear away some of the regulatory hurdles researchers face in being able to move the most promising therapies out of the lab and into clinical trials where they can be tested on people.

For the individuals and families affected by conditions like beta thalassemia and muscular dystrophy – potentially fatal genetic disorders – every day is Rare Disease Day. They live with the reality of these problems every single day. That’s why we are committed to working hard every single day, to find a treatment that can help them and their loved ones.

New Stem Cell Treatment for ALS May Slow Disease Progression

Exciting news was published this week that will give patients suffering from ALS, also known as Lou Gehrig’s disease, something to cheer about. The journal JAMA Neurology reported that a new stem cell treatment was successful in slowing disease progression in a small group of ALS patients in a Phase 2 clinical trial.

This is big news for a fatal, incurable disease that is well known for its progressive, degenerating effects on nerve cells in the brain and spinal cord. We’ve written about ALS a lot in the Stem Cellar, so if you want more background on the disease, read our “Progress to a Cure for ALS” blog.

A patient’s own stem cells can help

The stem cell therapy involves extracting mesenchymal stem cells from the bone marrow of ALS patients. These stem cells are then manipulated in culture into cells that secrete a growth factor called NeuroTrophic Factor (NTF), which helps keep nerve cells in the brain and spinal cord healthy and alive. The NTF-secreting stem cells (called NurOwn cells) are then transplanted back into the same ALS patient (making this an autologous stem cell therapy) by injection into either the spinal fluid or the muscles.

logoThe NurOwn method was developed by BrainStorm Cell Therapeutics, a biotech company based in the US and Israel. Clinical trials to test the safety and efficacy of NurOwn stem cells began in 2011 at the Hadassah Medical Organization (HMO). So far, 26 patients have participated in the trials both in the US and in Israel.

According to the JAMA publication, patients were monitored 3 months before and 6 months after they received stem cell transplants and 6 months after. Twelve of the 26 patients participated in an early stage of the trial (phase 1/2) to test the safety and tolerability of the stem cell therapy. The other 14 patients participated in a later stage (phase 2a), dose-escalating study where their modified stem cells were injected into both their spinal fluid and muscles. Following the treatment, the scientists looked at the safety profile of the transplanted stem cells and for signs of clinical improvement in patients such as their ease of breathing or ability to control their muscle movement.

Stem cell treatment is effective in most ALS patients

Results from the clinical trial showed that a majority of the patients benefitted from the NurOwn stem cell therapy. HMO Principle scientist and senior author on the study, Dr. Dimitrios Karussis, explained:

Dr. Dimitrios Karussis (Image credit: Israel21c)

Dimitrios Karussis (Israel21c)

“The results are very encouraging.  Close to 90% of patients who were injected intrathecally through the spinal cord fluid were regarded as responders to the treatment either in terms of their respiratory function or their motor disability.  Almost all of the patients injected in this way showed less progression and some even improved in their respiratory functions or their motor functions.”

A PRNewswire press release covering this study called the stem cell therapy the “first-of-its-kind treatment for treating neurodegenerative diseases.”

Not a cure just yet

This stem cell therapy will need to be tested in more patients before the it can be determined truly effective in slowing progression of ALS. And Dr. Karussis was quick to note that the NurOwn stem cell therapy isn’t a cure for ALS, but rather an early-stage therapy that will provide significant benefit to patients by slowing disease progression.

“I am optimistic that within the foreseeable future, we may provide a treatment to ALS patients that can slow down or stop the progression. I believe we are in the early stages of something new and revolutionary with this harvested stem cell infusion therapy.  While this is absolutely by no means a cure, it is the first step in a long process in that direction.  I see this treatment as being potentially one of the major future tools to treat degenerative diseases of the brain and spinal cord, in general.”

Other stem cell treatments for ALS in the works

A single stem cell therapy that could treat multiple neurodegenerative diseases would be extremely valuable to patients and doctors. However, it’s not clear that the “one ring to rule them all” scenario (couldn’t help making a Lord of the Rings reference) will play out well for all diseases that affect the brain and spinal cord. Luckily, Dr. Karussis and Brainstem Cell Therapeutics are not the only ones pursuing stem cell therapies for ALS.

Clive Svendsen has been on a 15-year quest to develop an ALS therapy

Clive Svendsen

CIRM is currently funding 21 studies (a total of $56.6 million) that use stem cells to either study ALS or to develop therapies to treat the disease. We wrote about one recent study by Clive Svendsen at Cedars Sinai which is using a combination of gene therapy and brain stem cells to deliver growth factors to protect nerve cells in the brain and spinal cord of ALS patients. Currently, Svendsen and his team are in the latter stages of research and hope to apply for FDA approval to test their therapy in patients in the near future. Svendsen told CIRM, “we will begin recruiting patients the first week we have approval.”


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Watch Spinal Cord Cells Take a Hike!

magic school busWhat exactly goes on inside the human body? If you asked this question to the children’s book character Ms. Frizzle, she would throw you into her Magic School Bus and take you on a wild ride “Inside the Human Body” to get you up close and personal with the different organs and structures within our bodies.

Ms. Frizzle had a wild imagination, but she was on to something with her crazy adventures. Recently, scientists took a page out of one of Ms. Frizzle children’s books and took their own wild ride to check out what’s going on with the human spinal cord.

In a paper published yesterday in Neuron, scientists from the Salk Institute in San Diego reported that they were able to watch spinal cord cells walk around the spine of mice in real-time. They used a special microscope that could track and record the movement of motor neurons, an important nerve cell that controls the movement of muscles in your body. What they found when they watched these cells was equivalent to a pot of gold at the end of the rainbow.

Check out their stunning movie here:

The scientists not only recorded the activity of these motor neurons, but they identified the other spinal cord cells that these neurons interact and make connections with. One of their most significant findings was a population of spinal cord cells that connected to a subtype of motor neurons to foster important muscle movements like walking.

Understanding how the different cells of the spinal cord work together is very important because it will allow scientists and doctors to figure out better ways to treat patients with spinal cord injuries or neurodegenerative diseases, like ALS, that affect motor neurons.

Senior author Samuel Pfaff commented in a press release on the importance of this study and how easy his team’s technology is to use:

Pfaff_S09

Samuel Pfaff

Using optical methods to be able to watch neuron activity has been a dream over the past decade. Now, it’s one of those rare times when the technology is actually coming together to show you things you hadn’t been able to see before. You don’t need to do any kind of post-image processing to interpret this. These are just raw signals you can see through the eyepiece of a microscope. It’s really a jaw-dropping kind of visualization for a neuroscientist.

While this study doesn’t provide a direct avenue for therapeutic development, it does pave the way for a better understanding of the normal, healthy processes that go on in the human spine. Having more knowledge of “what is right” will help scientists to develop better strategies to fix “what is wrong” in spinal cord injuries and diseases like ALS.


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