Sleep Deprivation Decreases Stem Cell Activity


We have all been there: You are at your computer, working hard and then a yawn hits you. Alternatively, you are on the phone late at night and you start to nod. We all have our late nights burning the midnight oil, but we need our shut-eye.

Now it turns out that sleep deprivation might wreak havoc with your stem cells. New research in mice might (let me emphasize, might) have profound implications for patients undergoing bone marrow stem cell transplants.

This research was led by Dr. Asya Rolls, who formerly worked as a postdoctoral research fellow at Stanford University, but is now an assistant professor at the Israel Institute of Technology.

With regards to the clinical implications of this work, Dr. Rolls said, “Considering how little attention we typically pay to sleep in the hospital setting, this finding is troubling. We go to all this trouble to find a matching donor, but this research suggests that if the donor is not well-rested it can impact the outcome of the transplantation. However, it’s heartening to think that this is not an insurmountable obstacle; a short period of recovery sleep before transplant can restore the donor’s cells’ ability to function normally.”

Rolls and her colleagues used laboratory mice for this study and broke them into two different groups. One group of mice was physically handled by members of the research team for four hours in order prevent them from going to sleep. The other group of mice were not handled and slept soundly in their cages. Then Rolls and her collaborators isolated bone marrow stem cells from the sleepless and well-rested mice. These bone marrow stem cells were then used to them to help reconstitute the bone marrow of twelve different mice that had been given radiation treatments that wiped out their bone marrow stem cells. It is important to note that these donor mice had bone marrow stem cells that glowed when put under a fluorescent light.

The irradiated mice were then examined eight and 16 weeks after they had received the bone marrow stem cell transplants. By taking blood samples, Roll and others measured the production of blood cells by the transplanted bone marrow stem cells. Mind you, the irradiated mice also received some of their own bone marrow stem cells in combination with the bone marrow stem cells from the donor mice. This was to help determine the percentage of blood cells made by the stem cells from the donor mice. Surveys of the blood cells of the irradiated mice showed that donated stem cells from the mouse donors that had a good night’s sleep gave rise to about 26 percent of the examined blood cells. However, bone marrow stem cells from sleepless donor mice only produced approximately 12 percent of the surveyed blood cells.

Next, the Stanford team investigated the ability of the transplanted stem cells to find their way to the bone marrow of the recipient mice, twelve hours after transplantation. When the bone marrow of the donor mice was subjected to fluorescent light, the 3.3 percent of the bone marrow stem cells were from the well-rested donor mice. However, the same experiment in those recipient mice that had received mice had received bone marrow stem cells from the sleep-deprived mice showed that only 1.7 percent of the stem cells in the bone came from the donor mice. Thus the bone marrow stem cells from those mice that had a good night’s sleep were twice as likely to find their way to the bone marrow of the recipient.

When hematopoietic stem cells from the donor mice were tested in culture, stem cells from the sleepless mice showed a weak response to chemical cues found in bone marrow that activate migration to the bone marrow. Conversely, hematopoietic stem cells from the well-rested mice responded much more robustly to these same chemical cues and migrated appropriately.

Think of it; not sleeping for only four hours can decrease the activity of transplanted bone marrow stem cells by up to half. Remember that bone marrow stem cells contain the coveted hematopoietic stem cell population that produces all the blood cells coursing through our bloodstream. When transplanted into recipient animals (or patients), these stem cells must actively find their way to the bone marrow, take up residence there, and begin to produce all the blood cells necessary for the life and health of the recipient. Therefore even a small reduction in the health or activity of hematopoietic stem cells could drastically affect the success of the bone marrow transplant procedure.

Are the effects of sleeplessness permanent? Not at all, at least in mice. Rolls and her team showed that the decrease in bone marrow stem cell activity could be reversed by allowing the sleep-deprived mice to sleep. In fact, in the hands of Rolls and her co-workers, even letting mice get only two hours of recovery sleep effectively restored the activity of their bone marrow stem cells to properly reconstitute the bone marrow of a recipient in a bone marrow transplant procedure.

“Everyone has these stem cells, and they continuously replenish our blood and immune system,” said Rolls. “We still don’t know how sleep deprivation affects us all, not just bone marrow donors. The fact that recovery sleep is so helpful only emphasizes how important it is to pay attention to sleep.”

Bone marrow transplants are used to treat patients with blood cancers, immune system disorders or others types of conditions. Each year, many thousands of bone marrow transplant procedures are performed. Therefore refining the bone marrow stem cell transplant procedure is essential to helping patients who need such a procedure.

This study was published in Nature Communications, with Asya Rolls as the lead author, who did her work in the laboratory of Irving Weissman, the director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine.

Clincal Trial Validates Stem Cell-Based Treatments of Sickle Cell Disease in Adults


Santosh Saraf and his colleagues at the University of Illinois have used a low-dose irradiation/alemtuzumab plus stem cell transplant procedure to cure patients of sickle-cell disease. 12 adult patients have been cured of sickle-cell disease by means of a stem cell transplantation from a healthy, tissue-matched donor.

This new procedure obviates the need for chemotherapy to prepare the patient to receive transplanted cells and offers the possibility of curing tens of thousands of adults from sickle-cell disease.

Sickle cell disease is an inherited disease that primarily affects African-Americans born in the United States. The genetic lesion occurs in the beta-globin gene that causes hemoglobin molecules to assemble into filaments under low-oxygen conditions. These hemoglobin filaments deform red blood cells and cause them to plug small capillaries in tissues, causing severe pain, strokes and even death.

Fortunately, a bone marrow transplant from a healthy donor can cure sickle-cell disease, but few adults undergo such a procedure because the chemotherapeutic agents that are given to destroy the patient’s bone marrow leaves from susceptible to diseases, unable to make their own blood cells, and very weak and sick.

Fortunately, a gentler procedure that only partially ablate the patient’s bone marrow was developed at the National Institutes of Health ()NIH) in Bethesda, Maryland. Transplant physicians there have treated 30 patients, with an 87% success rate.

In the Phase I/II clinical trial at the University of Illinois, 92% of the patients treated with this gentler procedure that was developed at the NIH.

Approximately 90% of the 450 patients who received stem cells transplants for sickle-cell disease have been children. However, chemotherapy has been considered too risky for adult patients who are often weakened far more than children by it.

Adult sickle-cell patients live an average of 50 years with a combinations of blood transfusions and pain medicines to manage the pain crisis. However, their quality of life can be quite low. Now, with this chemotherapy-free procedure, adults with sickle-cell disease can be cured of their disease within one month of their transplant. They can even go back to work or school and operate in a pain-free fashion.

In the new procedure, patients receive immunosuppressive drugs just before the transplant, with a very low dose of whole body radiation. Alemtuzumab (Campath, Lemtrada) is a monoclonal antibody that binds to the CD52 glycoprotein on the surfaces of lymphocytes and elicits their destruction, but not the hematopoietic stem cells that gives rise to them.  Next, donor cells from a healthy a tissue-matched sibling or donor are transfused into the patient. Stem cells from the donor home to the bone marrow and produce healthy, new blood cells in large quantities. Patients must continue to take immunosuppressive drugs for at least a year.

In the University of Illinois trial, 13 patients between the ages of 17-40 were given transplants from the blood of a healthy, tissue-matched sibling. Donors must be tested for human leukocyte antigen (HLA) markers on the surfaces of cells. Ten different HLA markers must match between the donor and the recipient for the transplant to have the best chance of evading rejection. Physicians have transplanted two patients with good HLA matches, to their donor, but had a different blood type than the donor. In many cases, the sickle cells cannot be found in the blood after the transplant.

In all 13 patients, the transplanted cells successfully engrafted into the bone marrow of the patients, but one patient failed to follow the post-transplant therapy regimen and reverted to the original sickle-cell condition.

One year after the transplantation, the 12 successfully transplanted patients had normal hemoglobin concentrations in their blood and better cardiopulmonary function. They also reported significantly less pain and improved health and vitality,

For of the patients were able to stop post-transplantation immunotherapy, without transplant rejection or other complications.

“Adults with sickle-cell disease can be cured with chemotherapy – the main barrier that has stood in the way for so long,” said Damiano Rondelli, Professor of Medicine and Director of the Stem Cell Transplantation Program at the University of Illinois. “Our data provide more support that this therapy is safe and effective and prevents patients from living shortened lives, condemned to pain and progressive complications.”

These data were published in the journal Biology of Blood and Marrow Transplantation, 2015; DOI 10.1016/j.bbmt.2015.08.036.

Bone Marrow Pretreatment with Hypomethylating Agents Improves Progression-Free Survival in Leumemia Patients


When patients have certain types of leukemia, they can be cured if they receive a bone marrow transplant from a healthy donor. The immune cells from the donated bone marrow will then attack the cancer cells vigorously, and the leukemia will slip into remission.

Such a strategy is called an “allogeneic bone marrow transplant,” and it is an effective way to treat some types of leukemia. However, this technique is risky and it usually involves some patient-related mortality. The problem is getting the transplanted cells to survive.

A new study from the University of Texas MD Anderson Cancer Center in Houston, Texas has examined over eighty patients who have received allogeneic bone marrow grafts for chronic myelomonocytic leukemia (CMML). Stefan O. Ciurea and his colleagues have identified a new pre-treatment that seems to decrease the degree of tumor relapse.  Their study was published in the Biology of Blood and Bone Marrow Transplantation.

83 consecutive patients with some form of CMML received an allogeneic bone marrow transplants between April 1991 and December 2013 were examined in detail. They asked if pre-treatment of the bone marrow stem cells with chemicals called “hypomethylating agents” before transplant improved progression-free survival.

Seventy-eight patients received “induction treatment” before transplant, 37 received hypomethylating agents and 41 received cytotoxic chemotherapy. Patients treated with a hypomethylating agent had a significantly lower cumulative incidence of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03). However, the transplant-related mortality 1 year post-transplant did not significantly differ between these groups (27% and 30%, respectively; p=0.84). The lower relapse rate resulted in a significantly higher 3-year progression-free survival rate in patients treated with a hypomethylating agent (43%) than in those treated with other agents (27%; p=0.04).

This study supports the use of hypomethylating agents before allogeneic stem cell transplantation for patients with CMML to achieve remission and improve progression-free survival of patients. Of course future studies are needed to confirm these findings, but they suggest that pretreating bone marrow stem cells with hypomethylating agents prior to transplanting them will beef the cells up and help them life longer to fight tumors.

Adding Cyclosporin to Bone Marrow Might Increase Stem Cell Numbers, Quality, and Engraftment Efficiency


In the bone marrow, we have an army of blood cell-making stem cells called hematopoietic stem cells (HSCs) that make all the blood cells that course through our blood vessels. These cells divide throughout our lifetimes, and they replacement themselves while they generate all the red and white cells found in our blood.

hematopoietic-stem-jpg

HSCs are also the cells that are harvested during bone marrow aspirations and biopsies. Transplantation of HSCs can save the lives of patients with blood cancers or other types of blood-or bone marrow-based diseased.

Harvesting and transplanting HSCs is, therefore, a very important clinical strategy for treating many different types of blood disorders and diseases. However, this crucial strategy is limited by the relative rarity of HSCs in isolated bone marrow. Additionally, the number and function of HSCs deteriorate both during their collection from the bone marrow (BM) and during their manipulation outside the body. Fortunately, the development of culture conditions that best mimic the environment these cells experience in bone marrow (the so-called “HSC niche environment”) may help to minimize this loss.

Scanning electron microscopy of stem cells (yellow / green) in a scaffold structure (blue) serving as a basis for the artificial bone marrow.
Scanning electron microscopy of stem cells (yellow / green) in a scaffold structure (blue) serving as a basis for the artificial bone marrow.

One of the most important variables for HSC viability is oxygen concentration, since various studies have shown that the oxygen concentrations found in ambient air seems to be damaging to HSCs, which normally are found in rather oxygen-poor reaches in bone marrow. Researchers from the laboratory of Hal Broxmeyer at the Indiana University School of Medicine have discovered that HSCs suffer from ‘‘extra-physiologic oxygen shock/stress (EPHOSS)” if they are harvested under ambient oxygen conditions. On top of that, treatment of the collected HSCs with the immunosuppressant drug cyclosporin A (CSA) can inhibit this stress, enhance the yield of collected HSCs, and increase their transplantation efficiency.

When Broxmeyer and his colleagues compared mouse BM that had been harvested under normal oxygen concentrations (21% O2) and low-oxygen concentrations (3% O2), they observed that the hypoxic (low-oxygen) treatment caused a 5-fold increase in the number of Long Term (LT) self-renewing HSCs, and a decrease in harmful reactive oxygen species (ROS) and mitochondrial activity. Broxmeyer and others also confirmed the positive effect of hypoxia on HSC collection from human cord blood. When mouse BM collected under different conditions were assayed by competitive transplantation, the “hypoxic HSCs” engrafted more efficiently in recipient mice. This increased engraftment was not due to enhanced homing or reduced cell death. Instead it seems that the stress response to non-physiological oxygen concentrations (EPHOSS) has a rapid and significant damaging effect in HSCs.

Broxmeyer decided to take this study one step further. In mitochondria (the powerhouse of the cell), increased expression of the mitochondrial permeability transition pore (MPTP) seems to be one of the key mechanism by which oxidative stress affects HSCs.

mitochondrial permeability transition pore
mitochondrial permeability transition pore

Induction of the MPTP leads to mitochondrial swelling and uncoupled energy production (which leads to the generation of reactive oxygen species, otherwise known as “free radicals). This leads to cell death apoptosis and necrosis, and intermittent MPTP activation may also decrease stem cell function in general without killing the cells. Broxmeyer and his coworkers came upon a rather ingenious idea to use the drug cyclosporin A (CSA) to antagonize MPTP induction, since CSA inhibits the associated CypD (cyclophilin) protein. When HSCs were collected under high-oxygen conditions in the presence of CSA, there was a 4-fold increase in the recovery of LT-HSCs and enhanced engraftment levels compared to HSCs harvested in high-oxygen conditions without CSA. This link was further strengthened by examining the HSCs of mice with a deletion of the CypD gene. In these mice, HSCs collected under high-oxygen conditions showed increased LT-HSC recovery and decreased LT-HSC ROS levels compared to wild-type mice.

Cyclophilin
Cyclophilin

How, harvesting and processing HSCs from bone marrow in a low-oxygen environment within a transplant clinic is generally not possible. However, given the observed advantages, the application of CSA may represent an easy and attractive alternative. The authors of this paper (which was published in the journal Cell) note that CSA is already used in the clinic as an immunosuppressant. Therefore, this technique could potentially be rapidly adapted into bone marrow harvesting techniques.

An additional thought is that studies that use other types of stem cells for transplantation might also need to consider the effects of EPHOSS and oxygen concentration while preparing their cells in other model systems.

See “Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock” from Cell by Stuart P. Atkinson

Genetically Engineered Stem Cells to Treat Osteoporosis in Mice


Osteoporosis is a nasty condition characterized by weak and brittle bones often leading to devastating bone fractures and other injuries. Unfortunately, millions of people worldwide have been diagnosed with osteoporosis.

Osteoporosis

Contrary to popular belief, out bones are dynamic organs that undergo constant remodeling consisting of bone resorption and renewal. However, once bone resorption rates outpace bone renewal, bone densities decrease, which puts bones at risk of fractures. Medical researchers are would like to find new ways to not only discourage bone resorption, but generate new bone material to replace demineralized bone. Ideally, therapies would rejuvenate bone growth so that it the bone reverts back to its original density levels.

Now a promising strategy to accomplish this goal is relies on stem cell therapy. A collaborative study by Xiao-Bing Zhang and his colleagues from Loma Linda University and Jerry L. Pettis from the Memorial VA Medical Center has built on their prior work with genetically modified hematopoietic stem cells (HSCs) that identified a growth factor that caused a 45% increase in bone strength in mouse models. This work was published in the journal Proceedings of the National Academy of Sciences, USA.

Zhang and his coworkers wanted to find a gene therapy that promotes bone growth while minimizing side effects. To that end, Zhang’s group focused on a growth factor called PGDFB or “platelet-derived growth factor, subunit B.” The properties of this growth factor make it a promising candidate, since it is already FDA approved for treating bone defects in the jaw and mouth.

platelet-derived growth factor, subunit B
platelet-derived growth factor, subunit B

First, Zhang and others isolated HSCs from the bone marrow of donor mice. HSCs were chosen because they can be given intravenously, after which they will home in to one of the major sites of bone loss (the endosteal bone surface). The isolated HSCs were then genetically engineered to overexpress the growth factor PGDFB. Experimental mice were then irradiated to wipe out their own HSCs, and then these same mice were transplanted with the modified HSCs.

After four weeks, the upper leg bones of the mice (femur) were tested. Zhang and his colleagues found that PGDFB promoted new trabecular bone formation, but because the PGDFB was expressed at high levels, it negatively affected bone mineral density. Zhang and others then used weaker promoters to optimize the dosage of PGDFB expression in the HSCs. They discovered that the phosphoglycerate kinase promoter (PGK) worked well to mitigate the amount of PGDFB that is expressed in cells. When these HSCs were transplanted into irradiated mice, they observed increases in trabecular bone volume, thickness, and number as well as increases in connectivity density. Additionally, cortical bone volume increased by 20-30% while cortical porosity was reduced by 40%. Importantly, the lower dosage of PGDFB resulted in no observed decreases in bone mineral density due to osteomalacia or hyperparathyroidism.

These treated femurs and a control sample underwent three-point mechanical testing to test the integrity of the new bone. The PGK-PGDFB-treated femur displayed a 45% increase in maximum load-to-failure in the midshaft of the femur and a 46% increase in stiffness, indicating quality bone formation. Thus the new bone that is deposited it also of high quality.

The next step in this work would like to determine why this combination of a PGK promotor and PDGFB worked so well. Zhang and others have discovered that PDGFB promotes bone marrow mesenchymal stem cell formation and angiogenesis, which are two important factors in bone growth. They also found that optimizing the dosage of PDGFB is quite important for promoting osteoblast (bone-forming) cell formation.

Finally Zhang’s group investigated how osteoclastogenesis, or the creation of cells that reabsorb bone (osteoclasts) is affected by PDGFB with a PGK promotor. The treated femurs also had an increase in biomarkers for osteoclasts. This increase in both osteoblasts and osteoclasts indicates that the treated bones undergo the normal bone rebuilding and remodeling cycle.

Overall, this research provides a compelling investigational pathway for future cell therapies to treat osteoporosis. Mouse models show a fast-acting technique that result in bone formation and increasing bone strength.

Supercharging Stem Cells for Organ Transplant Patients


A biomedical research team at the University of Adelaide has designed a novel protocol for culturing stem cells that drives the cells to grow faster and become therapeutically stronger. This research was recently published in the international journal, Stem Cells, and is expected to lead to new treatments for transplant patients.

Kisha Sivanathan , a PhD student at the University of Adelaide’s School of Medicine and the Renal Transplant Unit at the Royal Adelaide Hospital, spoke about this exciting breakthrough in stem cell research: “Adult mesenchymal stem cells, which can be obtained from many tissues in the body including bone marrow, are fascinating scientists around the world because of their therapeutic nature and ability to cultivate quickly. These stem cells have been used for the treatment of many inflammatory diseases but we are always looking for ways in which to increase stem cells’ potency,” said Ms. Sivanathan, who is the lead author on this study.

Ms. Sivanathan continued: “Our research group is the first in the world to look at the interaction between mesenchymal stem cells and IL-17, a powerful protein that naturally occurs in the body during times of severe inflammation (such as during transplant rejection). We discovered that when cultured mesenchymal stem cells are treated with IL-17 they grow twice as fast as the untreated stem cells and are more efficient at regulating the body’s immune response.”

Stem cell therapy continues to show very promising signs for transplant patients and according to Ms Sivanathan, the IL-17 treated stem cells could potentially be even more effective at preventing and treating inflammation in transplant recipients. The particular goal in this case is to treat patients who have received organ transplants; and even help control organ rejection in transplant patients.

“Current drugs (immunosuppressant drugs) used to help prevent a patient rejecting a transplant suppress the whole immune system and can cause severe side effects, like cancer. However, stem cell therapy (used in conjunction with immunosuppressant drugs) helps patients ‘accept’ transplants while repairing damaged tissue in the body, resulting in less side effects,” says Ms Sivanathan. “We are yet to undertake clinical trials on the IL-17 treated stem cells but we anticipate that because this treatment produces more potent stem cells, they will be more effective than the untreated stem cells,” she said.

Gene Therapy/Stem Cell Treatment Cures Boys of Severe Genetic Disease


British doctors have successfully cured youngsters suffering from a deadly inherited genetic disorder using ground-breaking stem cell-based treatments. This is the harbinger of a new era of medicine and genetic therapies.

The young patients who participated in this trial suffer from the most severe form of a rare blood condition call “Wiskott-Aldrich Syndrome.” The trial participants have now been free of the disease for four years.

Patients with Wiskott-Aldrich syndrome are usually male, and they have a deficient immune system that fails to fight off common infections that usually do not affect most people and a reduced ability to form blood clots. The numbers, and size of platelets in the blood, which are the cells responsible for initiating blood clots, are abnormal in individuals with Wiskott-Aldrich syndrome; they have very small platelets and few of them. This condition is called microthrombocytopenia. This platelet abnormality leads to easy bruising or episodes of prolonged bleeding following minor traumas. Additionally, many types of white blood cells are abnormal or nonfunctional, and this increases the risk of several immune and inflammatory disorders. Often patients with Wiskott-Aldrich syndrome develop eczema, which is an inflammatory skin disorder characterized by abnormal patches of red, irritated skin. Affected individuals also have an increased susceptibility to infection, and developing autoimmune disorders. They also have an increased chance of developing some types of cancer, such as cancer of the immune system cells (lymphoma).

Wiskott-Aldrich syndrome is inherited from the X chromosome, and therefore, the condition is much more common in males than in females. Having said that, Wiskott-Aldrich syndrome is still a rather rare condition, with an estimated incidence of 1 – 10 cases per million males worldwide.

Mutations in the WAS gene cause Wiskott-Aldrich syndrome. The WAS gene encodes the WASP protein, which is found in all blood cells, and relays signals from the surface of blood cells to the actin cytoskeleton inside the cell. The actin cytoskeleton is a network of fibrous proteins that compose the cell’s interior structural framework. WASP signaling triggers cell movement and attachment to other cells and tissues. In white blood cells, WASP signaling induces the actin cytoskeleton to establish the interactions between cells and the foreign invaders targeted by them. Mutations in the WAS gene cause a lack of any functional WASP protein, and loss of WASP signaling. Thus white blood cells are less able to respond to foreign invaders, which cause many of the immune problems related to Wiskott-Aldrich syndrome. Similarly, decreased WASP function impairs platelet development, leading to reduced size and early cell death.

In the Britain, Wiskott-Aldrich syndrome affects fewer than one hundred children in Britain, but Daniel Wheeler, 15, of Bristol is one of them. Wheeler was among seven children who participated in the new gene therapy trial at centers in London and Paris.

Daniel was diagnosed with Wiskott-Aldrich syndrome when he was two years old and needed frequent medical care to manage his symptoms which included severe eczema, asthma and inability to fight infections. David’s older brother died from complications associated with the disease. However, since undergoing gene therapy in 2011 Daniel has shown no symptoms and doctors believe he is effectively cured.

Daniel’s mother Sarah, 50, who works in real estate in Bristol said: “Since being around two, Daniel has been in an out of hospital, but now his skin has cleared up and so has his asthma. It means he can get on with his life now.”

Adrian Thrasher, Professor in Pediatric Immunology, at Great Ormond Street Hospital in London, where David’s treatment was carried out, said that it offered new hope for people suffering from incurable disease. “We are entering a new era where genetic treatments are entering mainstream medicine and offering hope to patients for whom conventional treatments don’t work well or are simply unavailable,” he said.

“The work shows that this method is successful in patients who, in the past would have very little chance of survival without a well match bone marrow donor.

“It also excitingly demonstrates the potential for treatment of a large number of other diseases for which existing therapies are either unsatisfactory or unavailable.”

In this trial, David’s bone marrow stem cells were isolated and subjected to gene therapy in the laboratory. The faulty WAS gene was replaced with a healthy copy of the gene. These genetically repaired stem cells were replaced in David’s bone marrow where they began producing healthy blood cells that were free from the disease. Because the healthy blood cells were more durable and lived longer than the diseases ones, they eventually overtook the diseased ones.

Seven children between the ages of eight months and 15 years were selected for the trial because a bone marrow match could not be found. Without bone marrow transplantation, patients usually do not survive their teenage years. All the children had eczema and associated recurrent infections and most experienced severe bleeding and autoimmune disease that, in one case, confined the child to a wheelchair.

The children went from spending an average of 25 days in the hospital to no days in the hospital in the two years after the treatment. Furthermore the child using the wheelchair was able to walk again.

Fulvio Mavilio, Chief Scientific Officer at Genethon, the biotech company which developed the treatment said: “It is the first time that a gene therapy based on genetically modified stem cells is tested in an international clinical trial that shows a reproducible and robust therapeutic effect in different centers and different countries.”