Multiple sclerosis

Cashing in on COVID-19

/ Kevin McCormack / Leave a comment
Coronavirus particles, illustration. Courtesy KTSDesign/Science Photo Library

As the coronavirus pandemic continues to spread, one of the few bright spots is how many researchers are stepping up and trying to find new ways to tackle it, to treat it and hopefully even cure it. Unfortunately, there are also those who are simply trying to cash in on it.

In the last few years the number of predatory clinics offering so-called “stem cell therapies” for everything from Alzheimer’s and multiple sclerosis to autism and arthritis has exploded in the US. The products they offer have not undergone a clinical trial to show that they work; they haven’t been approved by the US Food and Drug Administration (FDA); they don’t have any evidence they are even safe. But that doesn’t stop them marketing these claims and it isn’t stopping some of them from now trying to cash in on the fears created by the coronavirus.

One company is hawking what it calls a rapid COVID-19 test, one that can determine if you have the virus in under ten minutes (many current tests take days to produce a result). All it takes is a few drops of blood and, from the comfort of your own home, you get to find out if you are positive for COVID-19. And best of all, it claims it is 99 percent accurate.

What could be the problem with that? A lot as it turns out.

If you go to the bottom of the page on the website marketing the test it basically says “this does not work and we’re not making any claims or are in any way responsible for any results it produces.” So much for 99 percent accurate.

It’s not the only example of this kind of shameless attempt to cash in on COVID-19. So it’s appropriate that this week the Alliance for Regenerative Medicine (ARM), issued a statement strongly condemning these attempts and the clinics behind them.

ARM warns about the growing number of “stem cell clinics” (that) are taking advantage of the “hype” around stem cells – and, in certain cases, the current concern about COVID-19 – and avoiding regulation by falsely marketing illegal and potentially harmful products to patients seeking cures.” 

These so called “therapies” or tests do more than just take money – in some cases tens of thousands of dollars – from individuals: “Public health is at risk when unscrupulous providers offer stem cell products that are unapproved, unproven and fail to adhere to established rules for good manufacturing practices. Many of these providers put patients at risk by falsely marketing the benefits of treatments, and often promoting the stem cells for conditions that are outside of their area of medical expertise.”

It’s sad that even in times when so many people are working hard to find treatments for the virus, and many are risking their lives caring for those who have the virus, that there are unscrupulous people trying to make money out of it. All we can do is be mindful, be careful and be suspicious of anything that sounds too good to be true.

There are no miracle cures. No miracle treatments. No rapid blood tests you can order in the mail. Be aware. And most importantly of all, be safe.

The CIRM Board recently held a meeting to approve $5 million in emergency funding for rapid research into potential treatments for COVID-19.

Old cells need not apply: how a stem cell’s age can impact potential treatments

/ Yimy Villa / 2 Comments

Getting older is a normal, at times existential, part of life. The outward changes are abundant and noticeable: thinning of the hair, greying of the hair, and added lines to the face. There are also changes that happen that are not so abundantly clear in terms of outward appearance: slowing of healing time for bone fractures and a gradual loss of bodily function. The process of aging poses one very fundamental question — Could understanding how stem cells age lead to a greater understanding of how diseases develop? More importantly, could it guide the approach towards developing potential treatments? Two different studies highlight the importance of evaluating and understanding the process of aging in stem cells.

The first study, led by Dr. Michael Fehlings, looked at the impact of donor age in relation to stem cell therapies for spinal cord injuries (SCI). Dr. Fehlings, with a team of investigators from the University of Toronto and Krembil Research Institute, University Health Network, used an adult rat model to look at how cells derived from young vs. old stem cells affected tissue regeneration and recovery after a spinal cord injury.

Some rats with a SCI received cells derived from stem cells in the umbilical cord blood, which are considered “young” stem cells. The other rats with a SCI received cells derived from stem cells in the bone marrow, which are considered “old” stem cells. The results showed, ten weeks after treatment, that rats given the “young” stem cells exhibited a better recovery in comparison to those given the “old” stem cells.

In a press release, Dr. Fehlings stated that,

“Together, this minimally invasive and effective approach to cell therapy has significant implications on the treatment of traumatic cervical SCI and other central nervous system injuries. These results can help to optimize cell treatment strategies for eventual use in humans.”

The full results to this study were published in Stem Cells Translational Medicine.

The second, separate study, conducted by Dr. Stephen Crocker at UConn Health, looks at brain stem cells in people with multiple sclerosis (MS), a neurodegenerative disease caused by the inflammation and destruction of the insulation around the nerves, also known as myelin. Problems with insulation around the nerves can prevent or complicate the electrical signals sent from the brain to the body, which can lead to problems with walking or other bodily movements.

Drawing of a healthy nerve cell with insulation (left) and one damaged by multiple sclerosis (right). Image courtesy of Shutterstock

Dr. Crocker and his team found that brain stem cells in patients with MS look much older when compared to the brain stem cells of a healthy person around the same age. Not only did these brain stem cells look older, but they also acted much older in comparison to their healthy counterparts. It was also discovered that the brain stem cells of MS patients were producing a protein that prevented the development of insulation around the nerves. What is more remarkable is that Dr. Crocker and his team demonstrated that when this protein is blocked, the insulation around the nerves develops normally again.

In a press release, Dr. Valentina Fossati, a neurologist at the New York Stem Cell Foundation who evaluated these brain stem cells, stated that,

“We are excited that the study of human stem cells in a dish led to the discovery of a new disease mechanism that could be targeted in much-needed therapeutics for progressive MS patients.”

The complete study was published in the Proceedings of the National Academy of Sciences (PNAS).

A new stem cell derived tool for studying brain diseases

/ Pallavi Penumetcha / Leave a comment
Sergiu Pasca’s three-dimensional culture makes it possible to watch how three different brain-cell types – oligodendrocytes (green), neurons (magenta) and astrocytes (blue) – interact in a dish as they do in a developing human  brain.
Courtesy of the Pasca lab

Neurological diseases are among the most daunting diagnoses for a patient to receive, because they impact how the individual interacts with their surroundings. Central to our ability to provide better treatment options for these patients, is scientists’ capability to understand the biological factors that influence disease development and progression. Researchers at the Stanford University School of Medicine have made an important step in providing neuroscientists a better tool to understand the brain.

While animal models are excellent systems to study the intricacies of different diseases, the ability to translate any findings to humans is relatively limited. The next best option is to study human stem cell derived tissues in the laboratory. The problem with the currently available laboratory-derived systems for studying the brain, however, is the limited longevity and diversity of neuronal cell types. Dr. Sergiu Pasca’s team was able to overcome these hurdles, as detailed in their study, published in the journal Nature Neuroscience.

A new approach

Specifically, Dr. Pasca’s group developed a method to differentiate or transform skin derived human induced pluripotent stem cells (iPSCs – which are capable of becoming any cell type) into brain-like structures that mimic how oligodendrocytes mature during brain development. Oligodendrocytes are most well known for their role in myelinating neurons, in effect creating a protective sheath around the cell to protect its ability to communicate with other brain cells. Studying oligodendrocytes in culture systems is challenging because they arise later in brain development, and it is difficult to generate and maintain them with other cell types found in the brain.

These scientists circumvented this problem by using a unique combination of growth factors and nutrients to culture the oligodendrocytes, and found that they behaved very similarly to oligodendrocytes isolated from humans. Most excitingly, they observed that the stem cell-derived oligodendrocytes were able to myelinate other neurons in the culture system. Therefore they were both physically and functionally similar to human oligodendrocytes.

Importantly, the scientists were also able to generate astrocytes alongside the oligodendrocytes. Astrocytes perform many important functions such as providing essential nutrients and directing the electrical signals that help cells in the brain communicate with each other. In a press release, Dr. Pasca explains the importance of generating multiple cell types in this in vitro system:

“We now have multiple cell types interacting in one single culture. This permits us to look close-up at how the main cellular players in the human brain are talking to each other.”

This in vitro or laboratory-developed system has the potential to help scientists better understand oligodendrocytes in the context of diseases such as multiple sclerosis and cerebral palsy, both of which stem from improper myelination of brain nerve cells.

This work was partially supported by a CIRM grant.

The most popular Stem Cellar posts of 2018

/ Kevin McCormack / 2 Comments

The blog

You never know when you write something if people are going to read it. Sometimes you wonder if anyone is going to read it. So, it’s always fun, and educational, to look back at the end of the year and see which pieces got the most eyeballs.

It isn’t always the ones you think will draw the biggest audiences. Sometimes it is diseases that are considered “rare” (those affecting fewer than 200,000 people) that get the most attention.

Maybe it’s because those diseases have such a powerful online community which shares news, any news, about their condition of interest with everyone they know. Whatever the reason, we are always delighted to share encouraging news about research we are funding or encouraging research that someone else is funding.

That was certainly the case with the top two stories this year. Both were related to ALS or Lou Gehrig’s disease.  It’s a particularly nasty condition. People diagnosed with ALS have a life expectancy of just 2 to 5 years. So it’s probably not a big surprise that stories suggesting stem cells could expand that life span got a big reception.

Whatever the reason, we’re just happy to share hopeful news with everyone who comes to our blog.

And so, without further ado, here is the list of the most popular Stem Cellar Blog Posts for 2018.

All of us in the Communications team at CIRM consider it an honor and privilege to be able to work here and to meet many of the people behind these stories; the researchers and the patients and patient advocates. They are an extraordinary group of individuals who help remind us why we do this work and why it is important. We love our work and we hope you enjoy it too. We plan to be every bit as active and engaged in 2019.

Adding the missing piece: “mini-brain” method now includes important cell type

/ Todd Dubnicoff / Leave a comment

Although studying brain cells as a single layer in petri dishes has led to countless ground-breaking discoveries in neurobiology, it’s pretty intuitive that a two-dimensional “lawn” of cells doesn’t fully represent what’s happening in our complex, three-dimensional brain.

In the past few years, researchers have really upped their game with the development of brain organoids, self-organizing balls of cells that more accurately mimic the function of particular parts of the brain’s anatomy. Generating brain organoids from induced pluripotent stem cells (iPSCs) derived from patient skin samples is revolutionizing the study of brain diseases (see our previous blog stories here, here and here.)

Copy of oligocortical_spheroids_in_wells

Tiny brain organoid spheres in petri dishes. Image: Case Western

This week, Case Western researchers reported in Nature Methods about an important improvement to the organoid technique that includes all the major cell types found in the cerebral cortex, the outer layer of the brain responsible for critical functions like our memory, language, and consciousness. The new method incorporates oliogodendrocytes, a cell type previously missing from the “mini-cortexes”. Oliogodendrocytes make myelin, a mix of proteins and fats that form a protective wrapping around nerve connections. Not unlike the plastic coating around an electrical wire, myelin is crucial for a neuron’s ability to send and receive signals from other neurons. Without the myelin, those signals short-circuit. It’s this breakdown in function that causes paralysis in multiple sclerosis patients and spinal cord injury victims.

With these new and improved organoids in hand, the researchers can now look for novel therapeutic strategies that could boost myelin production. In fact, the researchers generated brain organoids using iPSCs derived from patients with Pelizaeus-Merzbacher disease, a rare but fatal inherited myelin disorder. Each patient had a different mutation and an analysis of each organoid pointed to potential targets for drug treatments.

Dr. Mayur Madhavan, a co-first author on the study, explained the big picture implications of their new method in a press release:

Mayur Madhavan, PhD

“These organoids provide a way to predict the safety and efficacy of new myelin therapeutics on human brain-like tissue in the laboratory prior to clinical testing in humans.”

 

 

The story behind the book about the Stem Cell Agency

/ Kevin McCormack / Leave a comment

DonReed_BookSigning2018-35

Don Reed at his book launch: Photo by Todd Dubnicoff

WHY I WROTE “CALIFORNIA CURES”  By Don C. Reed

It was Wednesday, June 13th, 2018, the launch day for my new book, “CALIFORNIA CURES: How the California Stem Cell Research Program is Fighting Your Incurable Disease!”

As I stood in front of the audience of scientists, CIRM staff members, patient advocates, I thought to myself, “these are the kind of people who built the California stem cell program.” Wheelchair warriors Karen Miner and Susan Rotchy, sitting in the front row, typified the determination and resolve typical of those who fought to get the program off the ground. Now I was about to ask them to do it one more time.

My first book about CIRM was “STEM CELL BATTLES: Proposition 71 and Beyond. It told the story of  how we got started: the initial struggles—and a hopeful look into the future.

Imagine being in a boat on the open sea and there was a patch of green on the horizon. You could be reasonably certain those were the tops of coconut trees, and that there was an island attached—but all you could see was a patch of green.

Today we can see the island. We are not on shore yet, but it is real.

“CALIFORNIA CURES” shows what is real and achieved: the progress the scientists have made– and why we absolutely must continue.

For instance, in the third row were three little girls, their parents and grandparents.

One of them was Evangelina “Evie” Vaccaro, age 5. She was alive today because of CIRM, who had funded the research and the doctor who saved her.

Don Reed and Evie and Alysia

Don Reed, Alysia Vaccaro and daughter Evie: Photo by Yimy Villa

Evie was born with Severe Combined Immunodeficiency (SCID) commonly called the “bubble baby” disease. It meant she could never go outside because her immune system could not protect her.  Her mom and dad had to wear hospital masks to get near her, even just to give her a hug.

But Dr. Donald Kohn of UCLA operated on the tiny girl, taking out some of her bone marrow, repairing the genetic defect that caused SCID, then putting the bone marrow back.

Today, “Evie” glowed with health, and was cheerfully oblivious to the fuss she raised.

I was actually a little intimidated by her, this tiny girl who so embodied the hopes and dreams of millions. What a delight to hear her mother Alysia speak, explaining  how she helped Evie understand her situation:  she had “unicorn blood” which could help other little children feel better too.

This was CIRM in action, fighting to save lives and ease suffering.

If people really knew what is happening at CIRM, they would absolutely have to support it. That’s why I write, to get the message out in bite-size chunks.

You might know the federal statistics—133 million children, women and men with one or more chronic diseases—at a cost of $2.9 trillion dollars last year.

But not enough people know California’s battle to defeat those diseases.

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Adrienne Shapiro at the book launch: Photo by Todd Dubnicoff

Champion patient advocate Adrienne Shapiro was with us, sharing a little of the stress a parent feels if her child has sickle cell anemia, and the science which gives us hope:  the CIRM-funded doctor who cured Evie is working on sickle cell now.

Because of CIRM, newly paralyzed people now have a realistic chance to recover function: a stem cell therapy begun long ago (pride compels me to mention it was started by the Roman Reed Spinal Cord Injury Research Act, named after my son), is using stem cells to re-insulate damaged nerves in the spine.  Six people were recently given the stem cell treatment pioneered by Hans Keirstead, (currently running for Congress!)  and all six experienced some level of recovery, in a few cases regaining some use of their arms hands.

Are you old enough to remember the late Annette Funicello and Richard Pryor?  These great entertainers were stricken by multiple sclerosis, a slow paralysis.  A cure did not come in time for them. But the international cooperation between California’s Craig Wallace and Australia’s Claude Bernard may help others: by  re-insulating MS-damaged nerves like what was done with spinal cord injury.

My brother David shattered his leg in a motorcycle accident. He endured multiple operations, had steel rods and plates inserted into his leg. Tomorrow’s accident recovery may be easier.  At Cedars-Sinai, Drs. Dan Gazit and Hyun Bae are working to use stem cells to regrow the needed bone.

My wife suffers arthritis in her knees. Her pain is so great she tries to make only one trip a day down and up the stairs of our home.  The cushion of cartilage in her knees is worn out, so it is bone on bone—but what if that living cushion could be restored? Dr. Denis Evseenko of UCLA is attempting just that.

As I spoke, on the wall behind me was a picture of a beautiful woman, Rosie Barrero, who had been left blind by retinitis pigmentosa. Rosie lost her sight when her twin children were born—and regained it when they were teenagers—seeing them for the first time, thanks to Dr. Henry Klassen, another scientist funded by CIRM.

What about cancer? That miserable condition has killed several of my family, and I was recently diagnosed with prostate cancer myself. I had everything available– surgery, radiation, hormone shots which felt like harpoons—hopefully I am fine, but who knows for sure?

Irv Weissman, the friendly bear genius of Stanford, may have the answer to cancer.  He recognized there were cancer stem cells involved. Nobody believed him for a while, but it is now increasingly accepted that these cancer stem cells have a coating of protein which makes them invisible to the body’s defenses. The Weissman procedure may peel off that “cloak of invisibility” so the immune system can find and kill them all—and thereby cure their owner.

What will happen when CIRM’s funding runs out next year?

If we do nothing, the greatest source of stem cell research funding will be gone. We need to renew CIRM. Patients all around the world are depending on us.

The California stem cell program was begun and led by Robert N. “Bob” Klein. He not only led the campaign, was its chief writer and number one donor, but he was also the first Chair of the Board, serving without pay for the first six years. It was an incredible burden; he worked beyond exhaustion routinely.

Would he be willing to try it again, this time to renew the funding of a successful program? When I asked him, he said:

“If California polls support the continuing efforts of CIRM—then I am fully committed to a 2020 initiative to renew the California Institute for Regenerative Medicine (CIRM).”

Shakespeare said it best in his famous “to be or not to be” speech, asking if it is “nobler …to endure the slings and arrows of outrageous fortune, or to take arms against a sea of troubles—and by opposing, end them”.

Should we passively endure chronic disease and disability—or fight for cures?

California’s answer was the stem cell program CIRM—and continuing CIRM is the reason I wrote this book.

Don C. Reed is the author of “CALIFORNIA CURES: How the California Stem Cell Program is Fighting Your Incurable Disease!”, from World Scientific Publishing, Inc., publisher of the late Professor Stephen Hawking.

For more information, visit the author’s website: www.stemcellbattles.com

 

Could Stem Cells Help Beat Multiple Sclerosis?

/ Hamideh Emrani / 2 Comments

March is Multiple Sclerosis month. In honor of MS patients and research, we are featuring a guest blog from scientist and communicator Hamideh Emrani. Thoughts expressed here are not necessarily those of CIRM.

If you are reading this post, other than out of curiosity, chances are that you know someone who has been affected by Multiple Sclerosis (MS). This unpredictable and at times confusing disease has affected too many people in my circle of friends and family. I personally have spent hours reading about it and reading about possible treatments.

For instance, M, a really close friend of mine woke up one day and everything was blurry. She could see but it seemed as if there was a thick fog covering everything. After seeing her optometrist and being evaluated via multiple tests and an MRI scan, she was diagnosed with MS. The reason behind her blurred vision was inflammation of her optic nerves.

Why do MS symptoms happen?

The nerve cells in the brain and spinal cord are connected through cellular extensions. Each cell has one long cellular extension at one end, called an axon, that looks similar to an electrical wire. Axons relay information using neural signals from one cell to another. Just as an electrical wire has a protective plastic cover to avoid leakage of electricity, these axons, are covered with a protective layer of a special fat called myelin.

The myelin on the outside of nerve cells is destroyed in patients with MS. (Source Wikimedia & Bruce Blaus)

In MS, a patient’s immune cells start to attack this protective layer in the central nervous system: the optic nerves, brain, and the spinal cord. They also attack the cells that produce myelin (called oligodendrocytes) and the injured nerve axon fibers. This results in de-myelination or the loss of myelin; and eventual deterioration and damage of the nerve axons. In turn, multiple scar tissues form on the damaged areas on nerves that can be seen through MRI, hence the name “multiple sclerosis” with sclerosis meaning scar tissue.

Generally, the demyelination and scar tissue will cause communication problems among nerves and the symptoms vary in each patient making it a complicated disease to treat. Some common resulting symptoms include excessive fatigue, pain, blurred vision, walking difficulties, muscle  stiffness and changes in brain-based skills such as memory and problem solving.

Depending on the stage of the disease and the extent of the damage, the disease has been categorized to four different courses.

MS Type Description
Clinically Isolated Syndrome (CIS) The person has had one episode of neurological symptoms that may or may not be accompanied by damages seen in an MRI scan.

 
Relapsing remitting MS (RRMS) The most common type of MS, which is characterized by clearly defined periods of neurologic inflammation called “MS attacks” that can be followed by periods of partial or complete recovery. The person might be completely symptom free during these remission times.
Secondary progressive MS (SPMS) Many patients with RRMS over time transition to SPMS where there is no recovery from the symptoms and disability accumulates.

 
Primary progressive MS (PPMS) There are no remissions from the onset of the disease and disability caused by disease activity worsens over time.

What is the cause of MS?

MS is affecting a growing number of human populations. While the jury is still out to define the main cause, many scientists believe that various factors play a role such as genetic predisposition, viral and bacterial infections, and environmental cues. MS is mostly prominent in countries in the Northern hemisphere and colder climates. It affects more women than men, and is mostly diagnosed between the age of 35-50.

Treatments for MS

Unfortunately, there is no cure for MS at the moment. The drugs that are available, called MS modifying treatments, try to prevent the progression of the disease but they don’t reverse it. Instead, the drugs mostly modulate the immune system to avoid further attacks or treat symptoms such as fatigue, pain, and bladder issues that are caused by the damage.

How do stem cells come into picture?

Stem cells are unique cells with the ability to both self-renew and specialize into different cell types. This amazing regeneration ability has turned them into great sources for designing treatment strategies to replace the damaged cells in MS. Two stem cell treatment approaches for MS are currently in development. In one, the researchers try to reboot or modulate the patient’s immune system to prevent it from attacking the nerve cells. In the other, scientists focus on using stem cells to make oligodendrocytes to try and regenerate and repair lost and injured nervous tissue.

Overview of Recent Clinical Trials

The most common stem cells used in clinical trials are the blood, or haematopoietic stem cells (HSCs) which are isolated from the bone marrow. Haematopoietic stem cell transplants (HSCT) have been used for decades to treat blood cancers such as leukemias, but the first time they were studied for treating MS was in the 1990s.

In this method, the patient’s HSCs are collected from the bone marrow and stored. Then, the patient’s immune system, including the bone marrow, is completely depleted through chemotherapy. Finally, the stem cells are transplanted back into the body and after a few months eventually build up a new immune system.

Just last month, Dr. Paolo Muraro et al. published a report that reviews such clinical trials and the long-term outcomes for the patients. They evaluated data for 281 patients from 25 centers in 13 countries that were followed an average of 6.5 years after the transplant. At the end they conclude that almost half of the patients receiving HSCT did not have any progression of the disease. And, younger patients with the most common form of MS, RRMS, who had less disability going into the trial, and had gone through less disease modifying treatments had a better outcome. (73% were progression free at the  5 year mark).

Additionally, over the past two years three separate phase two clinical trials in Northern America have reported results:

  • In the HALT-MS trial, a small number (24) of patients with, RRMS, whose disease was not controlled by any medications, underwent HSCT. After 5 years, 91.3% of the patients did not show any sign of disease progression.
  • In June 2016, a Canadian team of researchers reported the results of a long term follow up of an aHSCT trial (the “a” stands for autologous, meaning it used the patient’s own cells) on 24 patients whose MS had progressed even after receiving conventional treatments. After up to 13 years after the transplantation, no relapses were evident, and 35% of the patients experienced reversals in their level of disability.
  • Back in 2015, Burt et al. reported their HSCT treatment regimen for 123 RRMS patients and their follow up of up to 4 years. In their study, instead of completely depleting the patient’s immune system, they just suppressed it and performed the transplants. Their data suggest that there was no disease progression in 87% of individuals who had MS for less than 10 years.

Will Stem Cells be used for treatment of MS in the near future?

Even though the initial results of the HSCT clinical trials sound promising, the risks that are involved are not easy to ignore.  In all the mentioned trials, there were side effects related to the transplant. There were also a total of nine deaths reported in all the studies combined (since 1990s). However, most of these deaths occurred before the year of 2000 and they were attributed to transplantation techniques and patient selection methods. Over the years, researchers have been working hard to fine tune the techniques and made the procedure safer. But even now it is important for the patients to weigh the benefits and the risks before undergoing the procedure.

That’s why neurologists and stem cell scientists do not currently recommend  blood stem cell transplants as the top-of-the-line treatment option for most MS patients. Other types of stem cells are being investigated for their potential in deriving oligodendrocytes and nerve cells to re-myelinate and repair the damaged ones. However, they are still in development and have not reached a clinical trial in people.

At the moment, many stem cell treatment approaches are all at the experimental level and more research is needed to completely prove them to be safe and effective. There are many trusted sources to get information from and the international society for stem cell research (ISSCR) has produced a great nine step guideline for patients and family members considering stem cell treatments. Also the national MS society website is a great resource for learning more about Multiple Sclerosis, including participating in clinical trial studies.

Hamideh Emrani

Hamideh Emrani is a science and technology communicator in Toronto, Canada. She is a graduate of UC Berkeley and has a Masters degree from the University of Toronto. You can follow Hamideh on Twitter.

Stories that caught our eye: stem cell transplants help put MS in remission; unlocking the cause of autism; and a day to discover what stem cells are all about

/ Kevin McCormack / Leave a comment

multiple-sclerosis

Motor neurons

Stem cell transplants help put MS in remission: A combination of high dose immunosuppressive therapy and transplant of a person’s own blood stem cells seems to be a powerful tool in helping people with relapsing-remitting multiple sclerosis (RRMS) go into sustained remission.

Multiple sclerosis (MS) is an autoimmune disorder where the body’s own immune system attacks the brain and spinal cord, causing a wide variety of symptoms including overwhelming fatigue, blurred vision and mobility problems. RRMS is the most common form of MS, affecting up to 85 percent of people, and is characterized by attacks followed by periods of remission.

The HALT-MS trial, which was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), took the patient’s own blood stem cells, gave the individual chemotherapy to deplete their immune system, then returned the blood stem cells to the patient. The stem cells created a new blood supply and seemed to help repair the immune system.

Five years after the treatment, most of the patients were still in remission, despite not taking any medications for MS. Some people even recovered some mobility or other capabilities that they had lost due to the disease.

In a news release, Dr. Anthony Fauci, Director of NIAID, said anything that holds the disease at bay and helps people avoid taking medications is important:

“These extended findings suggest that one-time treatment with HDIT/HCT may be substantially more effective than long-term treatment with the best available medications for people with a certain type of MS. These encouraging results support the development of a large, randomized trial to directly compare HDIT/HCT to standard of care for this often-debilitating disease.”

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Scripps Research Institute

Using stem cells to model brain development disorders. (Karen Ring) CIRM-funded scientists from the Scripps Research Institute are interested in understanding how the brain develops and what goes wrong to cause intellectual disabilities like Fragile X syndrome, a genetic disease that is a common cause of autism spectrum disorder.

Because studying developmental disorders in humans is very difficult, the Scripps team turned to stem cell models for answers. This week, in the journal Brain, they published a breakthrough in our understanding of the early stages of brain development. They took induced pluripotent stem cells (iPSCs), made from cells from Fragile X syndrome patients, and turned these cells into brain cells called neurons in a cell culture dish.

They noticed an obvious difference between Fragile X patient iPSCs and healthy iPSCs: the patient stem cells took longer to develop into neurons, a result that suggests a similar delay in fetal brain development. The neurons from Fragile X patients also had difficulty forming synaptic connections, which are bridges that allow for information to pass from one neuron to another.

Scripps Research professor Jeanne Loring said that their findings could help to identify new drug therapies to treat Fragile X syndrome. She explained in a press release;

“We’re the first to see that these changes happen very early in brain development. This may be the only way we’ll be able to identify possible drug treatments to minimize the effects of the disorder.”

Looking ahead, Loring and her team will apply their stem cell model to other developmental diseases. She said, “Now we have the tools to ask the questions to advance people’s health.”

A Day to Discover What Stem Cells Are All about.  (Karen Ring) Everyone is familiar with the word stem cells, but do they really know what these cells are and what they are capable of? Scientists are finding creative ways to educate the public and students about the power of stem cells and stem cell research. A great example is the University of Southern California (USC), which is hosting a Stem Cell Day of Discovery to educate middle and high school students and their families about stem cell research.

The event is this Saturday at the USC Health Sciences Campus and will feature science talks, lab tours, hands-on experiments, stem cell lab video games, and a resource fair. It’s a wonderful opportunity for families to engage in science and also to expose young students to science in a fun and engaging way.

Interest in Stem Cell Day has been so high that the event has already sold out. But don’t worry, there will be another stem cell day next year. And for those of you who don’t live in Southern California, mark your calendars for the 2017 Stem Cell Awareness Day on Wednesday, October 11th. There will be stem cell education events all over California and in other parts of the country during that week in honor of this important day.

 

 

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

/ Todd Dubnicoff / Leave a comment

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.

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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.

Stem Cell Stories that Caught our Eye: Multiple Sclerosis, Parkinson’s and Reducing the Risk of Causing Tumors

/ Don Gibbons / Leave a comment

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.

Cell therapy for Parkinson’s advancing to the clinic. A decade-long moratorium on the transplant of fetal nerve tissue into Parkinson’s patient will end in two months when the first patients in a large global trial will receive the cells. BioScience Technology did a detailed overview on the causes for the moratorium and the optimism about the time being right to try again. The publication also talks about what most people in the field believe will be the long-term solution: moving from scarce fetal tissue to nerve cells grown from readily available embryonic stem cells. The author’s jumping off point was a pair of presentations at the International Society for Stem Cell Research in June, which we wrote about at the time. But the BioScience piece provides more background on the mixed results of earlier studies and references to recent journal publications showing long term—as much as 20 year—benefit for some of those patients.

It goes on to describe multiple reasons why, once the benefit is confirmed with fetal cells, moving to stem cells might be the better way to go. Not only are they more readily available, they can be purified in the lab as they are matured into the desired type of early-stage nerve cell. Researchers believe that some of the side effects seen in the early fetal trials stemmed from the transplants containing a second type of cell that caused jerking movements known as dyskinesias. One stem cell trial is expected to start in 2017, which we discussed in June.

Immunity persists through a special set of stem cells. Our immune system involves so many players and so much cell-to-cell interaction that there are significant gaps in our understanding of how it all works. One of those is how we can have long-term immunity to certain pathogens. The T-cells responsible for destroying invading bugs remember encountering specific ones, but they only live for a few years, generally estimated at five to 15. The blood-forming stem cells that are capable of generating all our immune cells would not have memory of specific invaders so could not be responsible for the long term immunity.

Now, an international team from Germany and from the Hutchison Center in Washington has isolated a subset of so-called “memory T-cells” that have stem cell properties. They can renew themselves and they can generate diverse offspring cells. Researchers have assumed cells like this must exist, but could not confirm it until they had some of the latest gee-wiz technologies that allow us to study single cells over time. ScienceDaily carried a story derived from a press release from the university in Munich and it discusses the long-term potential benefits from this finding, most notably for immune therapies in cancer. The team published their work in the journal Immunity.

Method may reduce the risk of stem cells causing tumors. When teams think about transplanting cells derived from pluripotent stem cells, either embryonic or iPS cells, they have to be concerned about causing tumors. While they will have tried to mature all the cells into a specific desired adult tissue, there may be a few pluripotent stem cells still in the mix that can cause tumors. A team at the Mayo Clinic seems to have developed a way to prevent any remaining stem cells in transplants derived from iPS cells from forming tumors. They treated the cells with a drug that blocks an enzyme needed for the stem cells to proliferate. Bio-Medicine ran a press release from the journal that published the finding, Stem Cells and Development. Unfortunately, that release lacks sufficient detail to know exactly what they did and its full impact. But it is nice to know that someone is developing some options of ways to begin to address this potential roadblock.

Multiple sclerosis just got easier to study. While we often talk about the power of iPS type stem cells to model disease, we probably devote too few electrons to the fact that the process is not easy and often takes a very long time. Taking a skin sample from a patient, reprogramming it to be an iPS cell, and then maturing those into the adult tissue that can mimic the disease in a dish takes months. It varies a bit depending on the type of adult tissue you want, but the nerve tissue that can mimic multiple sclerosis (MS) takes more than six months to create. So a team at the New York Stem Cell Foundation has been working on ways to speed up that process for MS. They now report that they have cut the time in half. This should make it much easier for more teams to jump into the effort of looking for cures for the disease. ScienceCodex ran the foundations press release.