Texas Man Becomes First Adult in the U.S. to Receive Updated Stem Cell Transplant to Treat Leukemia
Chuck Dandridge, a Mansfield, Texas resident, became the first adult in the U.S. to receive a newly modified stem cell transplant that uses genetically engineered blood cells from a family member. The milestone was announced by researchers at UT Southwestern Medical Center’s Harold C. Simmons Comprehensive Cancer Center in Dallas, where the procedure was performed.
Dandridge’s medical journey began in 2013, with a routine doctor’s visit to check his cholesterol levels; lab tests revealed low blood counts and further testing confirmed Dandridge’s diagnosis of myelodysplastic syndrome, also called pre-leukemia or MDS. By 2014, the leukemia had progressed to acute myeloid leukemia (AML), which, according to the National Cancer Institute, affects more than 20,000 Americans annually.
Dandridge was referred to UT Southwestern’s Simmons Cancer Center, where his leukemia was tested for genetic mutations.
“We wanted to know whether he had specific mutations in his cancer cells,” says
Jon Dandridge, Madhuri Vusirikala, M.D., and Chuck Dandridge at the Simmons Cancer Center. Photo: UT Southwestern Medical Center.
Madhuri Vusirikala, M.D., Professor of Internal Medicine and the primary investigator of many UT Southwestern clinical trials related to bone marrow transplantation.
“We found a mutation called IDH 2, which causes the body to produce an abnormal protein that promotes excessive cell growth. If you can target that mutation and stop the abnormal protein from being produced, then cells start behaving normally.”
Dandridge enrolled in a UT Southwestern clinical trial for a therapy called AG-221. He took four pills each morning for the next eight months. During that time, Dandridge saw marked improvement although he did not go into complete remission, according to Vusirikala.
That success made him eligible for a potentially curative stem cell transplant. But finding a donor proved challenging.
“The best chance of finding a full match is usually a full sibling; however, Chuck has no full siblings,” Vusirikala says. Additionally, Dandridge is African American, and minorities are under-represented in the National Marrow Donor Registry—about 70 percent of registry donors are Caucasian. The search for an unrelated donor was unsuccessful.
Vusirikala says that he knew Dandridge’s daughter and his son would be at least a half match. Since using a same-sex donor is preferred, as it reduces the risk of complications, his son Jon, 31, emerged as the best choice. But the risk of graft-versus-host-disease (GvHD) following a transplant using a half-match is very high, so they needed a better way to deal with the GvHD risk.
Once again, Mr. Dandridge volunteered for a cutting-edge clinical trial, known as BP-001, which processed the stem cells used in the transplant to reduce the risk of rejection and engineered blood cells that can be targeted if GvHD develops after the transplant.
The processes being tested in BP-001 are in clinical development by Houston-based Bellicum Pharmaceuticals. The study is evaluating patients with blood cell cancers who have a peripheral blood stem cell transplant from a partially matched relative. Immune cells (T cells) from the related donor are separated from the rest of the stem cells and genetically engineered in the Bellicum laboratory, and then given to the patient along with the stem cell transplant.These engineered T cells are modified to include a suicide gene with the help of a retrovirus. If the patient develops GvHD after transplant, the side-effect can be treated by giving a drug called rimiducid to activate the suicide gene and cause the activated GvHD-causing cells to be eliminated. The stem cells given for the transplant were also processed prior to giving them back to Dandridge to reduce the risk of graft rejection as well as GvHD.
The genetically engineered blood cells were transplanted from Dandrige’s son, Jon, 31, to the father in three, two-hour infusions at William P. Clements Jr. University Hospital in July, 2015, and today the elder Mr. Dandridge’s leukemia is in remission. His immune system is recovering, and the former Norman, Oklahoma YMCA CEO is now mentoring first-time CEOs for the YMCA.
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Amazing Stem Cell Research Breakthroughs You Never Heard of
Scientists have been studying stem cells for decades, and many of their findings, all pretty remarkable, aren’t widely circulated. Periodically, we will share one of these stem cell research breakthroughs here on this blog.
Summary: The skin renews, heals wounds, and regenerates the hair that covers it thanks to a small group of stem cells. These cells continually produce new ones, which appear on the skin surface after a few days. A 2008, released online July 28, 2016, has identified two proteins that are fundamental to conserve skin stem cells, and shows that without these proteins these cells are lost. Researchers find that these proteins, Dnmt3a and Dnmt3b, are altered similarly to tumor cells found in leukemia, lung cancer and colon cancer, which may help researchers discover if the proteins contribute to tumor development.
Amazing stem cell breakthroughs
Section of the epidermis showing all its layers, with cell borders in green and cell nuclei in blue (photo: Melissa Mangione)
The first amazing stem cell research breakthrough you may never heard of is a 2008 study, published online July28, 2016 in the journal “Cell Stem Cell,” titled “Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis,” led by Catalan Institution for Research and Advanced Studies (CREA) researcher Salvador Aznar Benitah, initiated at the Institute for Research in Biomedicine (IRB Barcelona).
Researchers identify two proteins— Dnmt3a and Dnmt3b—fundamental to conserving skin stem cells.
The study examines the continuous regeneration of the skin and hair that covers it, thanks to a small group of stem cells. Study researchers identified two proteins— Dnmt3a and Dnmt3b—that are fundamental to conserving skin stem cells. “Without these proteins, skin stem cells are not activated and the stem cells collapse and disappear from the tissue,” according Benitah, head of the Stem Cells and Cancer lab at IRB Barcelona.
Lorenzo Rinaldi, a la Caixa PhD student and first author of the study, identified all the regions of the genome that harbors these proteins. Rinaldi has observed that these two proteins exert their activity on gene enhancers and super-enhancers. Researchers were surprised to see that the two proteins, which had previously been associated with gene repression through DNA methylation, are activated in the most transcriptionally active regions of stem cells.
Researchers observe Dnmt3a and Dnmt3b at the genomic level for the first time
“We had never observed this activity because we were unable to study the global distribution
of Dnmt3a and Dnmt3b at the genomic level,” Rinaldi says. “Thanks to advances in sequencing techniques, more researchers are observing the very mechanism that we have described.”Of the 12,000 gene enhancers in the genome, about 300 are super-enhancers related to stem cells. The two proteins exert their function in these regions in order to trigger the approx. 1,000 genes required for the self-renewing capacity of skin stem cells. By methylating the super-enhancer, these proteins trigger the first step of the machinery that leads to the amplified expression of these essential genes for the stem cell.
Link to cancer
Among the various features related to tumor cells are three components:
• these cells show altered DNA methylation.
• gene enhancers, in addition to the bodies of the genes themselves, are highly mutated. These observations have been made possible thanks to mass sequencing of tumor cell genomes.
• these two proteins, Dnmt3a and Dnmt3b, are altered in many types of tumors, such as those encountered in leukemia, lung cancer and colon cancer.
Each of these three components is associated with the development of various kinds of cancer. Given that these proteins activate gene expression enhancers through DNA methylation, researchers believe that further studies of them in cancer cells would be helpful in determining whether they participate in tumor development.
The study was funded by the Spanish Ministry of Economy and Competitiveness and ERDFs. Benitah’s lab is also supported by The European Council for Research (ERC), the Worldwide Cancer Research Foundation, the Fundació Marató de TV3, the Fundación Vencer el Cáncer, the Fundación Botín and the Government of Catalonia.
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Stem Cell “Tattoo” Technology Allows Researchers to Track Cell Implants Non-invasively
Researchers at the University of Toronto have developed a tracer ink—a “stem cell tattoo”—that provides the ability to monitor stem cells in unprecedented detail after they’re injected.
The research findings, titled “Bifunctional Magnetic Silica Nanoparticles for Highly Efficient Human Stem Cell Labeling,” was published in June in the Journal of Magnetic Resonance Imaging. Already emerging as an ideal probe for noninvasive cell tracking, the technology has the potential to revolutionize stem cell research by arming scientists with the ability to visually follow the pathways and effectiveness of stem cell therapies in the body, in real time.
“Tattoo” tracer can help further development of stem cell therapies
University of Toronto biomedical engineering professor Hai-Ling Margaret Cheng, a biomedical engineer who specializes in medical imaging, says the new technology allows researchers to actually see and track stem cells after they’re injected. Cheng hopes the technique will help expedite the development and use of stem cell therapies.
Working with colleague Xiao-an Zhang, an assistant professor of chemistry at the University of Toronto, Scarborough, Cheng developed a singular chemical compound known as a contrast agent that acts as a tracer. Composed of manganese, an element that naturally occurs in the body, this tracer compound, called MnAMP, bathes stem cells in a green solution, rendering them traceable inside the body under MRI.
Stem cell tracer ink allows long term cell tracking
The contrast agent “ink” first enters a stem cell by penetrating its membrane. Once inside, it stimulates a chemical reaction that prevents it from seeping out of the cell the same way it entered. Previous versions of contrast agents easily escaped cells. By establishing a way to contain the ink within the cell’s walls, the research team achieved the ability to track the cells long term once they are inside the body.
University of Toronto professor Margaret Cheng holds samples of a chemical compound that will create a new way to visualize stem cells inside the body. (Photo: Bernard Weil, Toronto Star)
According to Cheng, some basic contrast agents are already available for use in humans, but none are capable of tracking cells over a long period of time. Contrast agents work by illuminating the deepest and darkest corners of a person’s internal architecture so they appear clearly under X-rays, computed tomography (CT) scans and MRIs. An example of a currently used contrasting agent would be the barium sulfate solution given to patients to help diagnose certain disorders of the esophagus, stomach, or intestines.
The thick substance coats the esophagus and other areas of the body with an illuminating compound, making them visible in an x-ray or CT scan. But the barium solution is eliminated from the body within 2 – 3 days or less. Before the stem cell tattoo tracer ink was developed, surgery was the only option for scientists to get a literal glance of a cells’ destiny after it was injected into the body. Now, researchers can track the results in real time, without resorting to any invasive procedures.
“Before, we could not visually track the cells once they were introduced into the body,” Cheng says. “Now we have the ability to view cells in a non-invasive manner using MRI, and monitor them for potentially a very long time.”
Cell tracer technology still in developmental stage
Currently the tracer ink technology is still in the early development phase and requires more animal testing. Cheng is hopeful it can proceed to human clinical trials in about 10 years. While Cheng has already proven that tattooing an animal’s embryonic stem cell doesn’t affect its ability to transform into a functional heart cell, rat, or even a pig (which better represents a human’s size), larger models are up for evaluation next.
In those test cases, researchers will cut off and reduce blood flow in the animals to mimic the effects of damage caused by a human heart attack. Cardiac stem cells pre-tagged with Cheng’s ink tracer technology will then be injected into the damaged tissue. Using MRI to monitor the luminous inked stem cells in action, researchers can non-invasively follow where in the body they’re traveling and more easily determine if the new cells are responsible for restoring normal heart rhythm.
Before it can be tested in humans, the chemical tracer will also have to pass rigorous toxicology tests to ensure its safety.
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New Guidelines for Stem Cell Research and Therapies Aim to Protect Patients from Charlatan Quackery
Stem cell research has never been more advanced, and as a result many different types of treatments are currently offered on the market. Unfortunate
ly, some providers are practicing quackery in stem cell therapies, and an abundance of well-intentioned scientific and medical personnel are prematurely publicizing their work. These providers and publishers have cast an unfair shadow of mistrust on this very important branch of medical research and potential treatments.
On the other hand, the contributions of professional medical and stem cell societies and other organizations require self-regulation through accreditation and certification, development of standards, and creation of a platform for collaboration among stakeholders.
Professional Guidelines for responsible Stem Cell Research
International Society for Stem Cell Research (ISSCR) is the largest professional organization of stem cell scientists. In 2007, ISSCR impaneled a broad international taskforce to develop a set of professional guidelines for responsible translational stem cell research. Their principles include high standards of preclinical evidence, peer review, scrupulous review of clinical protocol by an Institutional Review Board (IRB), rigorous informed consent, and publication of results whether positive or negative.
The general scientific consensus is that most stem cell therapies are not ready for marketing or commercialization. But the industries that are providing these treatments are increasingly sophisticated and organized, and are challenging established regulatory frameworks.
The International Society for Cellular Therapy (ISCT) has an interest in the promotion of stem cell research and development, but it also is interested in a broader range of cell-based interventions such as immune cell interventions, reproductive medicine, and gene therapy. The ISCT taskforce has working groups on definitions, scientific evidence and biological rationale, laboratory cell processing, clinical practice, regulation, commercial implications, communications, and policy.
Develop terminology, define levels of scientific evidence in new guidelines for stem cell research
The key goals are to develop an appropriate terminology, define the levels of scientific evidence needed to justify routine use or commercialization of a stem cell therapy, address questions of “experimental” and “innovative” use, and understand the global regulatory landscape in order to identify gaps and contradictions.
The ISSCR published revised guidelines for research and clinical translation involving stem cells on May 12, 2016. These new guidelines update and combine guidelines on stem cell research and clinical translation previously issued in 2006 and 2008 Jonathan Kimmelman, Associate Professor of Biomedical Ethics at McGill University, chaired the ISSCR Guidelines Update Task Force. The task force was made up of 25 experts in basic research, clinical research, and bioethics, and received feedback from 85 external individuals and organizations.
2016 guidelines: covering new ground in stem cell research
The 2016 guidelines cover new ground in areas such as gene editing and induced pluripotent stem cells. They introduce a new focus on the communication of results. The task force recognizes that results and potential applications can be exaggerated, leading to distorted understandings of research outcomes in the scientific community, popular press, and among potential patients. The “14-day rule” limiting experimentation on human embryos or embryo-like structures is upheld in these guidelines, although one task-force member has suggested that this may soon be open to revision.
In May, 2016 ISSCR released the following list of all of the new topics addressed in the revised guidelines as part of the announcement of its report:
- Define an Embryo Research Oversight (EMRO) process to encompass both human embryonic stem cell research and human embryo research that may not explicitly pertain to stem cells or generating new stem cell lines;
- Exclude the generation of induced pluripotent stem cells (iPS cells) from specific stem cell research oversight, and instead call on the existing human subjects review processes to oversee donor cell recruitment (iPS cells behave like embryonic stem cells but are derived by reprogramming more differentiated tissue cells);
- Support laboratory-based research that entails gene editing of the nuclear genomes of human sperm, egg, or embryos, when performed under rigorous review, but hold that any attempt to apply this clinically would be premature and should be prohibited at this time;
- Define principles for evaluating both basic and clinically applied research on mitochondrial replacement therapy, in concordance with recent deliberations in the U.K., U.S., and elsewhere;
- Determine that where there is no undue financial inducement to participate, it may be acceptable to compensate women who donate eggs for research;
- Recognize that the development of increasingly complex in vitro models of early stages of human development should undergo specialized review;
- Highlight opportunities to strengthen preclinical studies in stem cell research, including reproducibility and stringent standards for experimental design;
- Call for robust standards for preclinical and clinical research evidence as clinical trials progress and rigorous evaluation for safety and efficacy before marketing approval;
- Address the valuable contributions made by patients or patient groups to support clinical research and a framework to ensure this is achieved without compromising the integrity of the research;
- Highlight the responsibility of all groups communicating stem cell science and medicine—scientists, clinicians, industry, science communicators, and media—to present accurate, balanced reports of progress and setbacks.
The good news is that stem cell research is evolving into a highly respected and in-demand branch of healing that many consider to be the future of medicine. Since pluripotent stem cells have the ability to differentiate into any type of cell, they are used in the development of medical treatments for a wide range of conditions including physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). Further treatments using stem cells are being developed due to stem cells’ ability to repair extensive tissue damage.
Great levels of success and potential have been achieved from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. Embryonic stem cells are pluripotent, which means they can become any cell type of the body, with the exception of placental cells. More and more is being discovered about the plasticity of adult stem cells, increasing the potential number of cell types an adult stem cell can become.
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Researchers Move Closer to Lung Stem Cell Therapies to Treat Chronic Lung Diseases
Chronic lung diseases are the third leading causes of death in the U.S. Chronic lung diseases include a collection of illnesses that cause airflow blockage and breathing-related issues, including primarily chronic obstructive pulmonary disease (COPD), bronchitis, emphysema and asthma. Lung disease involves changes in cells within the lungs, and while research on lung stem cell therapies may not only shed light on their causes, it may provide the groundwork for future treatments.
Stem cells in the lung
Human lungs are hard working organs. In an average lifetime, human lungs take 20-40 million breaths and experience a daily airflow of between 1,850 and 2,640 gallons. Human lungs are made up of two distinct regions:
- The conducting airway tubes, including the trachea, bronchi, and bronchioles.
- The gas exchange regions, or alveolar spaces.
Medical researchers have discovered that these regions each contain unique types of stem cells and progenitor cells. In normal lungs, an abundance of progenitor cells is present in each region, which divide to replace old or damaged lung cells to keep the lungs healthy. The progenitor cells include tracheal basal cells, bronchiolar secretory cells (known as club cells), and alveolar type 2 cells. Progenitor cell division is believed to be sufficient to renew the lung’s structure throughout normal adult life.
Stem cells are far less abundant than progenitors, but are found in both embryonic and adult lungs. Some stem cells assist in initial lung development, while others help repair and regenerate the lung throughout one’s lifetime. Problematic stem cells may actually contribute to lung diseases. In mouse lungs, certain rare stem cells have been located in the conducting airway tubes after to severe injury—for example, flu infection. These rare cells can divide and produce new cells that contribute to both the airway and gas exchange regions. These cells have also been grown in vitro and used as a proof-of-concept treatment in injured mouse lungs.
Wnt2+ CPPs (green cells) populate multiple cell lineages in the developing lung including airway and vascular smooth muscle. The smooth muscle of the branching airways and large blood vessels are stained in red.
Adult mesenchymal stem cells (hMSCs)
Adult human mesenchymal stem cells (hMSCs) are the focus of a number of clinical applications. The advantage of hMSCs is that they are immuno-modulatory— capable of modifying or regulating one or more immune functions—and versatile due to the anti-inflammatory and regenerative bioactive molecules they secrete.
hMSCs have the potential to orchestrate reparative processes in diseased or injured tissues. Much of the diversity and uniqueness of hMSCs is defined by their response to the environment of injured tissue. hMSCs are sensitive to their site-specific microenvironment, and scientists anticipate that these cells will deliver the bioactive agents in a site-specific manner quite different from the way pharmaceutical drugs work in the treatment of lung diseases.
hMSCs are non-hematopoietic, multi-potent progenitor cells with the capacity to generate bone marrow stromal cells as well as adipocytes, chondrocytes, and osteocytes in suitable tissue and other organ sites.
Studying lung stem cells sheds light on the causes of lung disease
A better understanding of lung stem cell and progenitor cell biology can improve our knowledge of how the healthy lung works. This in turn will shed light on the causes of lung diseases such as chronic obstructive pulmonary disease (COPD). Such research could lead to the development of new treatments for lung disease. In fact, lung stem cells may be used in future therapies to repair or regenerate the lungs of patients with severe lung damage or disease.
Current research
Lung stem cells have most frequently been identified and characterized in mice. Studies on mice have allowed researchers to identify the differences between embryonic and adult lung stem cells, discover the role of stem cells in lung repair, and investigate how changes to lung stem cells may lead to lung disease. A current focus of research includes testing if the same stem and progenitor cell populations can be identified in human lungs.
Identifying progenitor and stem cells before and after lung injury
Researchers are also working to determine the role of stem cells in various human lung diseases, including lung cancer and COPD. They have begun examining potential clinical applications of stem cell therapies with several ‘first-in-human’ studies to investigate whether lung stem cells might enhance organ replacement or regeneration in patients.
The future of stem cells in treating lung disease
As researchers continue to improve their understanding of the exact identity and function of human lung stem cells, the potential for clinical applications will be divulged. Researchers will identify methods to control lung stem cells, which can then be tested as treatments for lung diseases. Further research will also investigate the uses of lung stem cells for personalized medicine.
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Stem Cell Research and Stem Cell Therapy: When can stem cells be used to treat patients?
The difference between stem cell research and therapy is in the scientific evidence that supports therapeutic intervention to be beneficial for the patient.
Stem cells have the remarkable potential to develop into many different types of cells in the body during early life and growth. In addition, in many tissues, stem cells serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the individual is alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.
Stem cell research on adult stem cells
Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, such as the pancreas and the heart, stem cells only divide under special conditions.
Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic “somatic” or “adult” stem cells in stem cell research.
In 2006, researchers made a breakthrough by identifying conditions that would allow some specialized adult cells to be “reprogrammed” genetically to assume a stem cell-like state. This new type of stem cell is called induced pluripotent stem cells (iPSCs).
Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lungs, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.
Stem cell research for treating disease
Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.
Laboratory studies of stem cells enable scientists to learn about the cells’ essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.
Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.
In 1964, the World Medical Association developed the Declaration of Helsinki as a statement of
ethical principles for medical research involving human subjects. It includes research on identifiable human material and data, last amended in October 2013.
According to the Helsinki Declaration, in the treatment of an individual patient where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorized representative, may use an unproven intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering.
Intervention should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all cases, new information must be recorded and, where appropriate, made publicly available.
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Could stem cells offer the cure for muscular dystrophy?
The term muscular dystrophy (MD) refers to a group of disorders in which a genetic abnormality causes muscles responsible for controlling movement to become weak, and muscle mass to be lost. These inherited disorders usually affect voluntary (skeletal) muscles, although weakness can also extend to the muscles that control respiration and swallowing.
Given that the genetic mutations triggering MD interfere with the normal production of certain critical proteins, the body is not able to reverse muscle weakening or loss of mass, so even when the disease progresses slowly, it eventually affects one’s ability to walk in a more or less conducive manner.
Who is affected by muscular dystrophy?
In most cases MD appears in infancy, but it’s not uncommon for symptoms to start manifesting in teens or adults.
Muscle fibers formed in the lab by human mesoangioblasts (image: eurostemcell).
Although the manifestations are similar, their severity varies depending on the age at which the disease occurs. In some, the symptoms are mild and sufferers are able to continue living almost normally, while in others the ailment is extremely disabling and can lead to muscle wasting, loss of the ability to walk, and even death.
There are different kinds of muscular dystrophy, the most common and severe form being Duchenne muscular dystrophy (DMD) Caused by a genetic flaw or defect, Duchenne MD is more common in males than females [1} and affects about 1 in every 3,500 boys worldwide.
The onset of Duchenne muscular dystrophy occurs between the ages of 2 and 6, and evolves slowly. Muscles becoming weaker year after year, and the spine and limbs becoming progressively deformed. In most cases, children affected by this form of the disease become wheelchair dependent by the age of 12.
People suffering from Duchenne MD often die in their 20s, and those who survive usually experience some degree of cognitive impairment. The shortening of tendons and muscles limits the mobility of sufferers even more, and breathing and heart problems can occur.
Treatments for Duchenne muscular dystrophy
Muscular dystrophy is a genetic disorder where the muscle tissue wastes away and loses function. In the affected muscle (left), the tissue has become disorganized and the concentration of dystrophin (green), an important protein in normal muscle functioning, is greatly reduced. (Image: Wikipedia)
There is currently no known cure for DMD, but there are treatments that help to reduce some of the symptoms and strengthen the patient’s muscles to some degree. Physiotherapy is commonly used for slowing down the loss of muscle mass and for maintaining flexibility or reducing muscle stiffness. Steroids are also used to slow down muscle wasting, but the severe side effects of steroids often cause more harm than good, such as bone weakening or cardiovascular problems.
In a healthy organism, damaged muscles repair themselves thanks to a series of cells that include muscle stem cells, called satellite cells. In Duchene muscular dystrophy, the muscles lack dystrophin, the protein needed for maintaining the integrity of muscle fibers. Without this protein, the burden placed on the body’s naturally occurring muscle stem cells is too intense, rendering the cells unable to repair damaged muscle tissue or to generate new muscle mass to replace wasted mass [6].
For this reason, scar tissue and fat cells take the place of damaged muscle tissue, contributing to muscle weakening and, over time, cause muscles to lose their functional ability. Would it be possible for the damaged muscle fibers to regain their regenerative ability with help from transplanted stem cells?
Research suggests stem cells could be a potential solution for muscle wasting
(Click on image to enlarge) Considerable efforts are underway to develop drugs and biologics (cell and gene therapy) to address the primary problem in Duchenne—the absence of dystrophin. Restoring dystrophin or replacing dystrophin with replacement protein are considered foundational therapies.
Different strategies involving stem cells for muscular dystrophy may be on the horizon, research suggests. Scientists have been using stem cells isolated from muscle tissue, bone marrow and blood vessels in lab animals to regenerate muscle fibers that are deficient in dystrophin[3] and results are encouraging.
In 2006, researchers managed to restore mobility in two afflicted dogs using stem cells isolated from muscle blood vessels [4], and in 2007 scientists managed to treat Duchenne MD in research mice using a combination of genetic correction and stem cells [3]. The latter study showed that it is possible to correct the genetic error in the cells that no longer produce dystrophin protein, and inject corrected cells stimulating the regeneration of muscles.
Researchers at the Harvard Stem Cell Institute obtained similar results, demonstrating that transplanted muscle stem cells can improve function in mice with MD, while replenishing the stem cell population in muscle fibers [5].
Although it’s still too early to say whether stem cells can cure DMD in humans, it’s clear that there are some promising stem-cell-based approaches for Duchenne MD. One solution is to replace the defective stem cells with healthy stem cells, as these may be able to generate working muscle fibers to replace damaged muscle fibers .
A second solution would be to reduce the inflammation that speeds up the loss and weakening of muscles using certain types of stem cells [2]. Combined treatments, such as mixing stem cell therapies with gene therapies are also being tested and may prove successful in the near future.
References:
- http://www.mayoclinic.org/diseases-conditions/muscular-dystrophy/basics/definition/con-20021240
- http://www.eurostemcell.org/factsheet/muscular-dystrophy-how-could-stem-cells-help
- https://www.mda.org/disease/duchenne-muscular-dystrophy/research
- http://quest.mda.org/article/scientists-bullish-stem-cells-muscle-repair
- http://hsci.harvard.edu/stem-cells-used-treat-muscular-dystrophy-mice
- https://med.stanford.edu/news/all-news/2014/12/stem-cells-faulty-in-duchenne-muscular-dystrophy.html
http://www.mayoclinic.org/diseases-conditions/muscular-dystrophy/basics/definition/con-20021240
- http://www.eurostemcell.org/factsheet/muscular-dystrophy-how-could-stem-cells-help
- https://www.mda.org/disease/duchenne-muscular-dystrophy/research
- http://quest.mda.org/article/scientists-bullish-stem-cells-muscle-repair
- http://hsci.harvard.edu/stem-cells-used-treat-muscular-dystrophy-mice
- https://med.stanford.edu/news/all-news/2014/12/stem-cells-faulty-in-duchenne-muscular-dystrophy.html
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