Two rare diseases, two pieces of good news

Dr. Stephanie Cherqui

Last week saw a flurry of really encouraging reports from projects that CIRM has supported. We blogged about two of them last Wednesday, but here’s another two programs showing promising results.

UC San Diego researcher Dr. Stephanie Cherqui is running a CIRM-funded clinical trial for cystinosis. This is a condition where patients lack the ability to clear an amino acid called cystine from their cells. As the cystine builds up it can lead to multi-organ failure affecting the kidneys, eyes, thyroid, muscle, and pancreas.

Dr. Cherqui uses the patient’s own blood stem cells, that have been genetically corrected in the lab to remove the defective gene that causes the problem. It’s hoped these new cells will help reduce the cystine buildup.

The data presented at the annual meeting of the American Society of Cell and Gene Therapy (ASCGT) focused on the first patient treated with this approach. Six months after being treated the patient is showing positive trends in kidney function. His glomerular filtration rate (a measure of how well the kidneys are working) has risen from 38 (considered a sign of moderate to severe loss of kidney function) to 52 (mild loss of kidney function). In addition, he has not had to take the medication he previously needed to control the disorder, nor has he experienced any serious side effects from the therapy.

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Dr. Linda Marban of Capricor

Capricor Therapeutics also had some positive news about its therapy for people with Duchenne’s Muscular Dystrophy (DMD). This is a progressive genetic disorder that slowly destroys the muscles. It affects mostly boys. By their teens many are unable to walk, and most die of heart or lung failure in their 20’s. 

Capricor is using a therapy called CAP-1002, using cells derived from heart stem cells, in the HOPE-2 clinical trial.

In a news release Capricor said 12-month data from the trial showed improvements in heart function, lung function and upper body strength. In contrast, a placebo control group that didn’t get the CAP-1002 treatment saw their condition deteriorate.

Craig McDonald, M.D., the lead investigator on the study, says these results are really encouraging.  “I am incredibly pleased with the outcome of the HOPE-2 trial which demonstrated clinically relevant benefits of CAP-1002 which resulted in measurable improvements in upper limb, cardiac and respiratory function. This is the first clinical trial which shows benefit to patients in advanced stages of DMD for which treatment options are limited.”

You can read the story of Caleb Sizemore, one of the patients treated in the CIRM-funded portion of this trial.

Promising results from CIRM-funded projects

Severe Leukocyte Adhesion Deficiency-1 (LAD-1) is a rare condition that causes the immune system to malfunction and reduces its ability to fight off viruses and bacteria. Over time the repeated infections can take a heavy toll on the body and dramatically shorten a person’s life. But now a therapy, developed by Rocket Pharmaceuticals, is showing promise in helping people with this disorder.

The therapy, called RP-L201, targets white blood cells called neutrophils which ordinarily attack and destroy invading particles. In people with LAD-1 their neutrophils are dangerously low. That’s why the new data about this treatment is so encouraging.

In a news release, Jonathan Schwartz, M.D., Chief Medical Officer of Rocket, says early results in the CIRM-funded clinical trial, show great promise:

“Patients with severe LAD-I have neutrophil CD18 expression of less than 2% of normal, with extremely high mortality in early childhood. In this first patient, an increase to 47% CD18 expression sustained over six months demonstrates that RP-L201 has the potential to correct the neutrophil deficiency that is the hallmark of LAD-I. We are also pleased with the continued visible improvement of multiple disease-related skin lesions. The second patient has recently been treated, and we look forward to completing the Phase 1 portion of the registrational trial for this program.”

The results were released at the 23rd Annual Meeting of the American Society of Gene and Cell Therapy.

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These microscopic images show gene expression in muscle stem and progenitor cells as they mature from early development to adulthood (left to right). As part of this process, the cells switch from actively expressing one key gene (green) to another (violet); this is accompanied by the growth of muscle fibers (red).
Photo courtesy: Cell Stem Cell/UCLA Broad Stem Cell Research Center

When you are going on a road-trip you need a map to help you find your way. It’s the same with stem cell research. If you are going to develop a new way to treat devastating muscle diseases, you need to have a map to show you how to build new muscle stem cells. And that’s what researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA – with help from CIRM funding – have done.

The team took muscle progenitor cells – which show what’s happening in development before a baby is born – and compared them to muscle stem cells – which control muscle development after a baby is born. That enabled them to identify which genes are active at what stage of development.

In a news release, April Pyle, senior author of the paper, says this could open the door to new therapies for a variety of conditions:

“Muscle loss due to aging or disease is often the result of dysfunctional muscle stem cells. This map identifies the precise gene networks present in muscle progenitor and stem cells across development, which is essential to developing methods to generate these cells in a dish to treat muscle disorders.”

The study is published in the journal Cell Stem Cell.

Tiny organs grown from snake stem cells produce real venom

Researchers grew tiny venom glands from nine different snake species, including the cape coral cobra pictured above.
Photo Credit: Michael D. Kern/Science Source

Snake venom can be deadly without proper treatment. Interestingly enough, it may also hold the key for treatments against pain, high blood pressure, and cancer according to one analysis. Despite this, scientists still do not understand much about the biology behind the wide range of different snake venoms, which can make it challenging to develop effective treatments in the event of snake bites.

Fortunately, a new study by Dr. Hans Clevers and his team at the Hubrecht Institute in the Netherlands could significantly aid the understanding of snake venom. Dr. Clevers and his team were able to grow miniature snake venom glands using snake stem cells. What’s more remarkable is that these “mini-organs” produced real venom!

Miniature, lab-grown snake venom glands
 Photo Credit: Ravian van Ineveld/Princess Maxima Center

In an article posted in Science Magazine, Dr. Clevers talks about how his study was navigating uncharted waters.

“Nobody knew anything about stem cells in snakes. We didn’t know if it was possible at all.”

To produce these “mini-organs”, the researchers removed the stem cells from the venom glands of nine different types of snake and placed them in a mixture of growth factors that contained different hormones and proteins. It turns out that the snake stem cells responded to the same factors used on human and mouse stem cells.

Eventually, the stem cells grew into little clumps of tissue and when the researchers removed the growth factors, they started to change into the same kind of cells that produce venom in the glands of snakes. Additionally, they were able to find that these “mini-organs” expressed similar genes as those observed in real venom glands.

The scientists were even able to test the nature of the “mini-organ” venom as well. A chemical and genetic analysis of the venom revealed that it matched the one made by real snakes. After testing this venom on mouse muscle cells and rat neurons, they also found that it damaged these cells similar to real venom.

The type of toxins and concentration levels can vary drastically in snake venom, even within the same species. This can make developing treatments challenging since they can only be used to combat one type of venom.

Dr. Clevers and his team now plan to study the complexities of venom and venom glands by compiling a “biobank” of frozen organoids from venomous reptiles around the world that could help researchers find broader treatments. With the aid of their newly developed “mini-organs”, all of this can be done without the handling of live, dangerous snakes, some of which are rare and difficult to keep in captivity.

The full results of this study were published in Cell.

New findings about muscle stem cells reveals the potential for growing replacement organs

Chrissa Kioussi’s group at Oregon State University has made exciting advances in further unraveling the scientific mysteries of stem cells. In work detailed in Scientific Reports, this group found that muscle-specific stem cells actually have the ability to make multiple different cell types.

muscle_bicep_FaceBook_shutterstock_162592241

Pumping up our knowledge about muscle stem cells

Initially, this group was interested in understanding how gene expression changes during embryonic development of skeletal muscle. To understand this process, they labeled muscle stem cells with a kind of fluorescent dye, called GFP, which allowed them to isolate these cells at different stages of development.  Once isolated, they determined what genes were being expressed by RNA sequencing. Surprisingly, they found that in addition to genes involved in muscle formation, they also identified activation of genes involved in the blood, nervous, immune and skeletal systems.

This work is particularly exciting, because it suggests the existence of stem cell “pockets,” or stem cells that are capable of not only making a specific cell type, but an entire organ system.

In a press release, Dr. Kioussi said:

chrissa_kioussi

Chrissa Kioussi, PhD

“That cell populations can give rise to so many different cell types, we can use it at the development stage and allow it to become something else over time… We can identify these cells and be able to generate not one but four different organs from them — this is a prelude to making body parts in a lab.” 

This study is particularly exciting because it gives more credence to the idea that entire limbs can be reconstructed from a small group of stem cells. Such advances could have enormous meaning for individuals who have lost body parts due to amputation or disease.

Giving thanks to Caleb and all of our stem cell pioneers [Video]

For our last blog before the Thanksgiving holiday, we give thanks to the patients and their caregivers who are forging a path toward a new era of regenerative medicine therapies through their participation in CIRM-funded clinical trials.

Some of our trials are in the early stages which means they are mainly focused on safety. Participants go into these trials knowing that the cell therapy dose they receive will probably be too low to get any benefit for themselves. And in later trials, some patients will receive a placebo, or blank therapy, for comparison purposes. Even if a patient gets an effective dose, it may not work for them. So the decision to enroll in an experimental clinical trial is often a selfless act. Yet final approval of a therapy by the U.S. Food and Drug Administration (and other regulatory agencies around the world) depends on these brave souls and for that we are truly grateful.

So, with this Thanksgiving Day spirit in mind, we leave you with our latest video featuring Caleb Sizemore, a charming young man who epitomizes the courage of our clinical trial pioneers. At just 7 years old, Caleb was diagnosed with Duchenne Muscular Dystrophy (DMD), a degenerative muscle disease which makes it difficult for him to walk and climb stairs, has led to dangerous scarring of his heart muscle and carries a shortened life expectancy with most DMD patients not living past their 20s or 30s.

In a sit-down interview with us and in clips from his June 2017 presentation to the CIRM governing Board, Caleb talked about the impact of DMD on his life and his experience enrolling in Capricor Therapeutics’ CIRM-funded clinical trial. The trial is testing a stem cell therapy designed to repair the heart scarring that occurs with DMD. By the end of the three-minute video, I can assure you that you’ll be as captivated as we were by Caleb’s delightful, sincere and full-of-faith personality.

The life of a sleeping muscle stem cell is very busy

For biological processes, knowing when to slow down is as important as knowing when to step on the accelerator. Take for example muscle stem cells. In a healthy state, these cells mostly lay quiet and rarely divide but upon injury, they bolt into action by dividing and specializing into new muscle cells to help repair damaged muscle tissue. Once that mission is accomplished, the small pool of muscle stem cells is replenished through self-renewal before going back into a dormant, or quiescent, state.

muscle stem cell

Muscle stem cell (pink with green outline) sits along a muscle fiber. Image: Michael Rudnicki/OIRM

“Dormant” may not be the best way to describe it because a lot of activity is going on within the cells to maintain its sleepy state. And a better understanding of the processes at play in a dormant state could reveal insights about treating aging or diseased muscles which often suffer from a depletion of muscle stem cells. One way to analyze cellular activity is by examining RNA transcripts which are created when a gene is turned “on”. These transcripts are the messenger molecules that provide a gene’s instructions for making a particular protein.

By observing something, you change it
In order to carry out the RNA transcript analyses in animal studies, researchers must isolate and purify the stem cells from muscle tissue. The worry here is that all of the necessary poking of prodding of the cells during the isolation method will alter the RNA transcripts leading to a misinterpretation of what is actually happening in the native muscle tissue. To overcome this challenge, Dr. Thomas Rando and his team at Stanford University applied a recently developed technique that allowed them to tag and track the RNA transcripts within living mice.

The CIRM-funded study reported today in Cell Reports found that there are indeed significant differences in results when comparing the standard in vitro lab method to the newer in vivo method. As science writer Krista Conger summarized in a Stanford Medical School press release, those differences led to some unexpected results that hadn’t been observed previously:

“The researchers were particularly surprised to learn that many of the RNAs made by the muscle stem cells in vivo are either degraded before they are made into proteins, or they are made into proteins that are then rapidly destroyed — a seemingly shocking waste of energy for cells that spend most of their lives just cooling their heels along the muscle fiber.”

It takes a lot of energy to stay ready
Dr. Rando thinks that these curious observations do not point to an inefficient use of a cell’s resources but instead, “it’s possible that this is one way the cells stay ready to undergo a rapid transformation, either by blocking degradation of RNA or proteins or by swiftly initiating translation of already existing RNA transcripts.”

The new method provides Rando’s team a whole new perceptive on understanding what’s happening behind the scenes during a muscle stem cell’s “dormant” state. And Rando thinks the technique has applications well beyond this study:

Rando

Thomas Rando

“It’s so important to know what we are and are not modeling about the state of these cells in vivo. This study will have a big impact on how researchers in the field think about understanding the characteristics of stem cells as they exist in their native state in the tissue.”

 

 

Stem cell agency funds Phase 3 clinical trial for Lou Gehrig’s disease

ALS

At CIRM we don’t have a disease hierarchy list that we use to guide where our funding goes. We don’t rank a disease by how many people suffer from it, if it affects children or adults, or how painful it is. But if we did have that kind of hierarchy you can be sure that Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, would be high on that list.

ALS is a truly nasty disease. It attacks the neurons, the cells in our brain and spinal cord that tell our muscles what to do. As those cells are destroyed we lose our ability to walk, to swallow, to talk, and ultimately to breathe.

As Dr. Maria Millan, CIRM’s interim President and CEO, said in a news release, it’s a fast-moving disease:

“ALS is a devastating disease with an average life expectancy of less than five years, and individuals afflicted with this condition suffer an extreme loss in quality of life. CIRM’s mission is to accelerate stem cell treatments to patients with unmet medical needs and, in keeping with this mission, our objective is to find a treatment for patients ravaged by this neurological condition for which there is currently no cure.”

Having given several talks to ALS support groups around the state, I have had the privilege of meeting many people with ALS and their families. I have seen how quickly the disease works and the devastation it brings. I’m always left in awe by the courage and dignity with which people bear it.

BrainStorm

I thought of those people, those families, today, when our governing Board voted to invest $15.9 million in a Phase 3 clinical trial for ALS run by BrainStorm Cell Therapeutics. BrainStorm is using mesenchymal stem cells (MSCs) that are taken from the patient’s own bone marrow. This reduces the risk of the patient’s immune system fighting the therapy.

After being removed, the MSCs are then modified in the laboratory to  boost their production of neurotrophic factors, proteins which are known to help support and protect the cells destroyed by ALS. The therapy, called NurOwn, is then re-infused back into the patient.

In an earlier Phase 2 clinical trial, NurOwn showed that it was safe and well tolerated by patients. It also showed evidence that it can help stop, or even reverse  the progression of the disease over a six month period, compared to a placebo.

CIRM is already funding one clinical trial program focused on treating ALS – that’s the work of Dr. Clive Svendsen and his team at Cedars Sinai, you can read about that here. Being able to add a second project, one that is in a Phase 3 clinical trial – the last stage before, hopefully, getting approval from the Food and Drug Administration (FDA) for wider use – means we are one step closer to being able to offer people with ALS a treatment that can help them.

Diane Winokur, the CIRM Board Patient Advocate member for ALS, says this is something that has been a long time coming:

CIRM Board member and ALS Patient Advocate Diane Winokur

“I lost two sons to ALS.  When my youngest son was diagnosed, he was confident that I would find something to save him.  There was very little research being done for ALS and most of that was very limited in scope.  There was one drug that had been developed.  It was being released for compassionate use and was scheduled to be reviewed by the FDA in the near future.  I was able to get the drug for Douglas.  It didn’t really help him and it was ultimately not approved by the FDA.

When my older son was diagnosed five years later, he too was convinced I would find a therapy.  Again, I talked to everyone in the field, searched every related study, but could find nothing promising.

I am tenacious by nature, and after Hugh’s death, though tempted to give up, I renewed my search.  There were more people, labs, companies looking at neurodegenerative diseases.

These two trials that CIRM is now funding represent breakthrough moments for me and for everyone touched by ALS.  I feel that they are a promising beginning.  I wish it had happened sooner.  In a way, though, they have validated Douglas and Hugh’s faith in me.”

These therapies are not a cure for ALS. At least not yet. But what they will do is hopefully help buy people time, and give them a sense of hope. For a disease that leaves people desperately short of both time and hope, that would be a precious gift. And for people like Diane Winokur, who have fought so hard to find something to help their loved ones, it’s a vindication that those efforts have not been in vain.

Have scientists discovered a natural way to boost muscle regeneration?

Painkillers like ibuprofen and aspirin are often a part of an athlete’s post-exercise regimen after intense workouts. Sore muscles, aches and stiffness can be more manageable by taking these drugs – collectively called non-steroidal anti-inflammatory drugs, or NSAIDS – to reduce inflammation and pain. But research suggests that the anti-inflammatory effects of these painkillers might cause more harm than good by preventing muscle repair and regeneration after injury or exercise.

A new study out of Stanford Medicine supports these findings and proposes that a component of the inflammatory process is necessary to promote muscle regeneration. Their study was funded in part by a CIRM grant and was published this week in the Proceedings of the National Academy of Sciences.

Muscle stem cells are scattered throughout skeletal muscle tissue and remain inactive until they are stimulated to divide. When muscles are damaged or injured, an inflammatory response involving a cascade of immune cells, molecules and growth factors activates these stem cells, prompting them to regenerate muscle tissue.

Andrew Ho, Helen Blau and Adelaida Palla led a study that found drugs like aspirin and ibuprofen can inhibit the ability of muscle tissue to repair itself in mice. (Image credit: Scott Reiff)

The Stanford team discovered that a molecule called Prostaglandin E2 or PGE2 is released during the inflammatory response and stimulates muscle repair by directly targeting the EP4 receptor on the surface of muscle stem cells. The interaction between PGE2 and EP4 causes muscle stem cells to divide and robustly regenerate muscle tissue.

Senior author on the study, Dr. Helen Blau, explained her team’s interest in PGE2-mediated muscle repair in a news release,

“Traditionally, inflammation has been considered a natural, but sometimes harmful, response to injury. But we wondered whether there might be a component in the pro-inflammatory signaling cascade that also stimulated muscle repair. We found that a single exposure to prostaglandin E2 has a profound effect on the proliferation of muscle stem cells in living animals. We postulated that we could enhance muscle regeneration by simply augmenting this natural physiological process in existing stem cells already located along the muscle fiber.”

Further studies in mice revealed that injury increased PGE2 levels in muscle tissue and increased expression of the EP4 receptor on muscle stem cells. This gave the authors the idea that treating mice with a pulse of PGE2 could stimulate their muscle stem cells to regenerate muscle tissue.

Their hunch turned out to be right. Co-first author Dr. Adelaida Palla explained,

“When we gave mice a single shot of PGE2 directly to the muscle, it robustly affected muscle regeneration and even increased strength. Conversely, if we inhibited the ability of the muscle stem cells to respond to naturally produced PGE2 by blocking the expression of EP4 or by giving them a single dose of a nonsteroidal anti-inflammatory drug to suppress PGE2 production, the acquisition of strength was impeded.”

Their research not only adds more evidence against the using NSAID painkillers like ibuprofen and aspirin to treat sore muscles, but also suggests that PGE2 could be a natural therapeutic strategy to boost muscle regeneration.

This cross-section of regenerated muscle shows muscle stem cells (red) in their niche along the muscle fibers (green). (Photo courtesy of Blau lab)

PGE2 is already approved by the US Food and Drug Administration (FDA) to induce labor in pregnant women, and Dr. Blau hopes that further research in her lab will pave the way for repurposing PGE2 to treat muscle injury and other conditions.

“Our goal has always been to find regulators of human muscle stem cells that can be useful in regenerative medicine. It might be possible to repurpose this already FDA-approved drug for use in muscle. This could be a novel way to target existing stem cells in their native environment to help people with muscle injury or trauma, or even to combat natural aging.”

Could revving up stem cells help senior citizens heal as fast as high school seniors?

All physicians, especially surgeons, sport medicine doctors, and military medical corps share a similar wish: to able to speed up the healing process for their patients’ incisions and injuries. Data published this week in Cell Reports may one day fulfill that wish. The study – reported by a Stanford University research team – pinpoints a single protein that revs up stem cells in the body, enabling them to repair tissue at a quicker rate.

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Muscle fibers (dark areas surrounding by green circles) are larger in mice injected with HGFA protein (right panel) compared to untreated mice (left panel), an indication of faster healing after muscle injury.
(Image: Cell Reports 19 (3) p. 479-486, fig 3C)

Most of the time, adult stem cells in the body keep to themselves and rarely divide. This calmness helps preserve this important, small pool of cells and avoids unnecessary mutations that may happen whenever DNA is copied during cell division.

To respond to injury, stem cells must be primed by dividing one time, which is a very slow process and can take several days. Once in this “alert” state, the stem cells are poised to start dividing much faster and help repair damaged tissue. The Stanford team, led by Dr. Thomas Rando, aimed to track down the signals that are responsible for this priming process with the hope of developing drugs that could help jump-start the healing process.

Super healing serum: it’s not just in video games
The team collected blood serum from mice two days after the animals had been subjected to a muscle injury (the mice were placed under anesthesia during the procedure and given pain medication afterwards). When that “injured” blood was injected into a different set of mice, their muscle stem cells became primed much faster than mice injected with “uninjured” blood.

“Clearly, blood from the injured animal contains a factor that alerts the stem cells,” said Rando in a press release. “We wanted to know, what is it in the blood that is doing this?”

 

A deeper examination of the priming process zeroed in on a muscle stem cell signal that is turned on by a protein in the blood called hepatocyte growth factor (HGF). So, it seemed likely that HGF was the protein that they had been looking for. But, to their surprise, there were no differences in the amount of HGF found in blood from injured and uninjured mice.

HGFA: the holy grail of healing?
It turns out, though, that HGF must first be chopped in two by an enzyme called HGFA to become active. When the team went back and examined the injured and uninjured blood, they found that it was HGFA which showed a difference: it was more active in the injured blood.

To show that HGFA was directly involved in stimulating tissue repair, the team injected mice with the enzyme two days before the muscle injury procedure. Twenty days post injury, the mice injected with HGFA had regenerated larger muscle fibers compared to untreated mice. Even more telling, nine days after the HGFA treatment, the mice had better recovery in terms of their wheel running activity compared to untreated mice.

To mimic tissue repair after a surgery incision, the team also looked at the impact of HGFA on skin wound healing. Like the muscle injury results, injecting animals with HGFA two days before creating a skin injury led to better wound healing compared to untreated mice. Even the hair that had been shaved at the surgical site grew back faster. First author Dr. Joseph Rodgers, now at USC, summed up the clinical implications of these results :

“Our research shows that by priming the body before an injury you can speed the process of tissue repair and recovery, similar to how a vaccine prepares the body to fight infection. We believe this could be a therapeutic approach to improve recovery in situations where injuries can be anticipated, such as surgery, combat or sports.”

Could we help senior citizens heal as fast as high school seniors?
Another application for this therapeutic approach may be for the elderly. Lots of things slow down when you get older including your body’s ability to heal itself. This observation sparks an intriguing question for Rando:

“Stem cell activity diminishes with advancing age, and older people heal more slowly and less effectively than younger people. Might it be possible to restore youthful healing by activating this [HGFA] pathway? We’d love to find out.”

I bet a lot of people would love for you to find out, too.

A horse, stem cells and an inspiring comeback story that may revolutionize tendon repair

Everyone loves a good comeback story. Probably because it leaves us feeling inspired and full of hope. But the comeback story about a horse named Dream Alliance may do more than that: his experience promises to help people with Achilles tendon injuries get fully healed and back on their feet more quickly.

Dream Alliance

Dream Alliance was bred and raised in a very poor Welsh town in the United Kingdom. One of the villagers had the dream of owning a thoroughbred racehorse. She convinced a group of her fellow townsfolk to pitch in $15 dollars a week to cover the costs of training the horse. Despite his lowly origins, Dream Alliance won his fourth race ever and his future looked bright. But during a race in 2008, one of his back hoofs cut a tendon in his front leg. The seemingly career-ending injury was so severe that the horse was nearly euthanized.

It works in horses, how about humans?
Instead, he received a novel stem cell procedure which healed the tendon and, incredibly, the thoroughbred went on to win the Welsh Grand National race 15 months later – one of the biggest races in the UK that is almost 4 miles long and involves jumping 22 fences. Researchers at the Royal Veterinary College in Liverpool developed the method and data gathered from the treatment of 1500 horses with this stem cell therapy show a 50% decrease in re-injury of the tendon.

It’s been so successful in horses that researchers at the University College of London and the Royal National Orthopaedic Hospital are currently running a clinical trial to test the procedure in humans.  Over the weekend, the Daily Mail ran a news story about the clinical trial. In it, team lead Andrew Goldberg explained how they got the human trial off the ground:

“Tendon injuries in horses are identical to those in humans, and using this evidence [from the 1500 treated horses] we were able to persuade the regulators to allow us to launch a small safety study in humans.”

Tendon repair: there’s got to be another way

Achilles tendon connects the calf muscle to the heel bone

The Achilles tendon is the largest tendon in the body and connects the calf muscle to the heel bone. It takes on a lot of strain during running and jumping so it’s a well-known injury to professional and recreational athletes but injuries also occur in those with a sedentary lifestyle. Altogether Achilles tendon injury occurs in about 5-10 people per 100,000. And about 25%-45% of those injuries require surgery which involves many months of crutches and it doesn’t always work. That’s why this stem cell approach is sorely needed.

The procedure is pretty straight forward as far as stem cell therapies go. Bone marrow from the patient’s hip is collected and mesenchymal stem cells – making up a small fraction of the marrow – are isolated. The stem cells are transferred to petri dishes and allowed to divide until there are several million cells. Then they are injected directly into the injured tendon.

A reason to be cautiously optimistic
Early results from the clinical trial are encouraging with a couple of the patients experiencing improvements. The Daily Mail article featured the clinical trial’s first patient who went from a very active lifestyle to one of excruciating ankle pain due to a gradually deteriorating Achilles tendon. Though hesitant when she first learned about the trial, the 46-year-old ultimately figured that the benefits outweighed the risk. That turned out to be a good decision:

“I worried, because no one had ever had it before, except a horse. But I was more worried I’d end up in a wheelchair. The difference now is amazing. I can do five miles on the treadmill without pain, and take my dog Honey on long walks again.”

The researchers aren’t exactly sure how the therapy works but mesenchymal stem cells are known to release factors that promote regeneration and reduce inflammation. The first patient’s positive results are just anecdotal at this point. The clinical trial is still recruiting volunteers so definitive results are still on the horizon. And even if that small trial is successful, larger clinical trials will be required to confirm effectiveness and safety. It will take time but without the careful gathering of this data, doctors and patients will remain in the dark about their chances for success with this stem cell treatment.

Hopefully the treatment proves to be successful and ushers in a golden era of comeback stories. Not just for star athletes eager to get back on the field but also for the average person whose career, good health and quality of life depends on their mobility.