­

Scientists speed up muscle repair – could fight dystrophy

Wednesday, October 05, 2016 Baltimore, MD---Athletes, the elderly and those with degenerative muscle disease would all benefit from accelerated muscle repair. When skeletal muscles, those connected to the bone, are injured, muscle stem cells wake up from a dormant state and repair the damage. When muscles age, however, stem cell number and function declines, as do both tissue function and regenerative ability.  Carnegie’s Christoph Lepper and team*, including researchers from the University of Missouri, investigated muscle stem cell pool size. In particular, they asked if stem cell number could be increased, and if there would be any associated functional benefits. Using genetically modified mice, the scientists found that while a muscle’s size remained unchanged, it surprisingly, is capable of supporting a much greater number of these stem cells than previously thought. These “super-numeral” stem cells could repair injured muscle and were faster at it than when only normal numbers are present. The team also found that the increase in stem cells stunts the decline of weakened, degenerative muscles, potentially a boon for fighting muscular dystrophy. The study is published in the October 11, 2016, issue of eLife. Muscle stem cells, called satellite cells, are undifferentiated muscle cells that promote growth, repair and regeneration. As Lepper explained: “These satellite cells make up some 5-7% of all muscle cells and are essential to muscle regeneration. When a mouse is born, the satellite cells divide and differentiate for about 3 to 4 weeks driving tissue growth. They then go quiet until an injury is detected. The number of satellite cells set aside at this time appears to be relatively constant with regard to the host muscle tissue size. We wanted to see whether this ratio could be manipulated [...]

Scientists find way to create human stem cells with only 23 chromosomes, could revolutionize genetic research

BY DENIS SLATTERY, NEW YORK DAILY NEWS, Wednesday, March 16, 2016, 8:53 PM A scientific discovery unveiled Wednesday could revolutionize genetic research with new screening tools and therapies. Researchers from Columbia University Medical Center, the New York Stem Cell Foundation Research Institute and Hebrew University have found a way to create human stem cells with only 23 chromosomes, rather than the usual 46. Normally, cells with only 23 chromosomes, known as haploid cells, cannot divide on their own. Most cells in the body contain information in the form of DNA, packaged into two sets of chromosomes — one from each parent, called diploid cells. The haploid cells found in the study can be turned into any tissue in the human body, despite only containing one set of chromosomes. The discovery holds promise for therapies to treat a range of conditions, including cancer and infertility, and may even explain why humans reproduce sexually via two parents rather than one. It will allow researchers to study genetic mutations without the “interference” of the second set and help scientists discover how genes mutate and cause devastating diseases like cystic fibrosis, muscular dystrophy and Down syndrome. The study was published in the journal Nature.

Researchers resolve longstanding issue of components needed to regenerate muscle

By Susan Gammon, Ph.D. February 9, 2016 Researchers at SBP have conclusively identified the protein complex that controls the genes needed to repair skeletal muscle. The discovery clears up deep-rooted conflicting data and will now help streamline efforts towards boosting stem cell-mediated muscle regeneration. Such strategies could treat muscle degenerative diseases such as muscular dystrophies, and those associated with aging and cancer. The research, published in eLife, describes the essential role of a TBP-containing TFIID-protein complex in activating genes that regenerate muscle tissue, and shows that an alternative protein called TBP2 is not involved in this task in adult muscles. “Our discovery clarifies the identity of the ‘molecular switches’ that control the activation of muscle genes in muscle stem cells (MuSCs),” said Barbora Malecova, Ph.D., postdoctoral fellow in the laboratory of Pier Lorenzo Puri, M.D., Ph.D., professor in the Development, Aging and Regeneration Program at SBP, and first author of the article. “Understanding what drives muscle gene expression gives us insights into molecular targets for regenerative medicine-based interventions (drugs) to treat muscle degenerative disorders.” MuSCs are adult stem cells present in skeletal muscle tissue that become activated in response to muscle injury to regenerate damaged muscle. In healthy skeletal muscle, MuSCs promote self-healing to repair muscle from normal wear and tear. But in disease conditions like muscular dystrophies, genetic mutations lead to the loss of key structural proteins of muscle cells, which results in cell dysfunction. Cells with these mutations can’t sustain the chronic regeneration pressure imposed by the disease, eventually resulting in progressive muscle weakness and death. Transcription factors regulate the differentiation or “programming” of MuSCs into mature muscle cells. Targeting transcription factors to activate muscle gene expression is an emerging, promising approach to generate new [...]

Gene Therapy Treats All Muscles in the Body in Muscular Dystrophy Dogs; Human Clinical Trials Are Next Step

Oct. 22, 2015 Story Contact: Christian Basi COLUMBIA, Mo. ­— Muscular dystrophy, which affects approximately 250,000 people in the U.S., occurs when damaged muscle tissue is replaced with fibrous, fatty or bony tissue and loses function. For years, scientists have searched for a way to successfully treat the most common form of the disease, Duchenne Muscular Dystrophy (DMD), which primarily affects boys. Now, a team of University of Missouriresearchers have successfully treated dogs with DMD and say that human clinical trials are being planned in the next few years. “This is the most common muscle disease in boys, and there is currently no effective therapy,” said Dongsheng Duan, the study leader and the Margaret Proctor Mulligan Professor in Medical Research at the MU School of Medicine. “This discovery took our research team more than 10 years, but we believe we are on the cusp of having a treatment for the disease.” Patients with Duchenne muscular dystrophy have a gene mutation that disrupts the production of a protein known as “dystrophin.” Absence of dystrophin starts a chain reaction that eventually leads to muscle cell degeneration and death. Affected boys lose their ability to walk and breathe as they get older. This places significant limitations on individuals afflicted with the disease. Dystrophin also is one of the largest genes in the human body. “Due to its size, it is impossible to deliver the entire gene with a gene therapy vector, which is the vehicle that carries the therapeutic gene to the correct site in the body,” Duan said. “Through previous research, we were able to develop a miniature version of this gene called a microgene. This minimized dystrophin protected all muscles in the body of diseased mice.” However, it took [...]

Researchers Isolate Human Muscle Stem Cells

By Nicholas Weiler on September 22, 2015 UC San Francisco researchers have successfully isolated human muscle stem cells and shown that the cells could robustly replicate and repair damaged muscles when grafted onto an injured site. The laboratory finding paves the way for potential treatments for patients with severe muscle injury, paralysis or genetic diseases such as muscular dystrophy. “We’ve shown definitively that these are bona-fide stem cells that can self-renew, proliferate and respond to injury,” said Jason Pomerantz, MD, an assistant professor of plastic and reconstructive surgery at UCSF. The findings appeared Sept. 8 in the open access Cell Press journal, Stem Cell Reports. When muscles are badly damaged, they can lose the native populations of stem cells that are needed to heal. This has posed a major roadblock for treating patients crippled by muscle injury and paralysis, particularly in the critical small muscles of the face, hand and eye, Pomerantz said. Surgeons have shown remarkable success at restoring nerves in damaged muscles, but if the process takes too long the stem cell pool and capacity for regeneration is lost, these injured muscles fail to connect to the nerve tissue, causing their power to wither away. “This is partly why we haven’t had major progress in treating these patients in 30 years,” Pomerantz said. “We know we can get the axons there, but we need the stem cells for there to be recovery.” Grafted “Satellite Cells” Repair and Replace Damaged Muscles So-called “satellite cells” dot the borders of muscle fibers and – at least in mice – were known to act as stem cells to contribute to muscle growth and repair. Until now, however, it wasn’t clear whether human satellite cells worked the same way [...]

Engineering a permanent solution to genetic diseases

Aug. 10, 2015 - In his mind, Basil Hubbard can already picture a new world of therapeutic treatments for millions of patients just over the horizon. It’s a future in which diseases like muscular dystrophy, cystic fibrosis and many others are treated permanently through the science of genome engineering. Thanks to his latest work, Hubbard is bringing that future closer to reality. Basil Hubbard Photo Hubbard’s research, published in the journal Nature Methods ("Continuous directed evolution of DNA-binding proteins to improve TALEN specificity"), demonstrates a new technology advancing the field of genome engineering. The method significantly improves the ability of scientists to target specific faulty genes, and then “edit” them, replacing the damaged genetic code with healthy DNA. “There is a trend in the scientific community to develop therapeutics in a more rational fashion, rather than just relying on traditional chemical screens,” says Hubbard, an assistant professor of pharmacology in the University of Alberta’s Faculty of Medicine & Dentistry. “We’re moving towards a very logical type of treatment for genetic diseases, where we can actually say, ‘Your disease is caused by a mutation in gene X, and we’re going to correct this mutation to treat it’. “In theory, genome engineering will eventually allow us to permanently cure genetic diseases by editing the specific faulty gene(s).” Revolutionizing health care Genome engineering involves the targeted, specific modification of an organism’s genetic information. Much like how a computer programmer edits computer code, scientists could one day replace a person’s broken or unhealthy genes with healthy ones through the use of sequence-specific DNA binding proteins attached to DNA-editing tools. The field has made large strides over the last two decades and may one day revolutionize medical care. One of [...]

Potential treatment for muscular dystrophy

Harvard Gazette, by Hadley Bridger, Brigham & Women's Hospital ~ August 3, 2015 Skeletal muscle is one of the most abundant tissue types in the human body, but it has proven difficult to produce in large quantities in the lab. Unlike other cell types, such as heart cells, neurons, and cells found in the gut, previous attempts to efficiently and accurately derive muscle cells from precursor cells or culture have not been fruitful. In a new study published this week in Nature Biotechnology, investigators from Harvard-affiliated Brigham and Women’s Hospital (BWH) report that by identifying and mimicking important developmental cues, they have been able to drive cells to grow into muscle fibers, producing millimeter-long fibers capable of contracting in a dish and multiplying in large numbers. This new method of producing muscle cells could offer a better model for studying muscle diseases, such as muscular dystrophy, and for testing potential treatment options. Previous studies have used genetic modification to create small numbers of muscle cells in the lab, but the researchers, led by investigators from BWH and the Harvard Stem Cell Institute, wanted a technique that would allow them to grow large numbers of muscle cells efficiently for use in clinical applications. “We took the hard route: We wanted to recapitulate all of the early stages of muscle cell development that happen in the body and re-create that in a dish in the lab,” said corresponding author Olivier Pourquie of Harvard Medical School’s Department of Genetics and BWH’s Department of Pathology. “We analyzed each stage of early development, and generated cell lines that glowed green when they reached each stage. Going step by step, we managed to mimic each stage of development and coax cells [...]

A New Grasp on Robotic Glove

Mon, 06/08/2015 - 10:15am- Harvard University The soft robotic glove could help patients suffering from muscular dystrophy, amyotrophic lateral sclerosis, incomplete spinal cord injury, or other hand impairments regain some independence and control of their environment. (Photo: Courtesy of Wyss Institute at Harvard University)Having achieved promising results in proof-of-concept prototyping and experimental testing, a soft robotic glove under development by Conor Walsh and a team of engineers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and Wyss Institute for Biologically Inspired Engineering could someday help people suffering from loss of hand motor control regain some of their independence. Most patients with partial or total loss of their hand motor abilities due to muscular dystrophy, amyotrophic lateral sclerosis (ALS), or incomplete spinal cord injury report a greatly reduced quality of life because of their inability to perform many activities of daily living. Tasks often taken for granted by the able-bodied — buttoning a shirt, picking up a telephone, using cooking and eating utensils — become frustrating, nearly impossible feats due to reduced gripping strength and motor control. The stage is now set for that to change, however, thanks to Walsh’s expertise in soft, wearable robotic systems and a development approach that involves the glove’s potential end users in every step of testing and development. The holistic approach ensures that technology development goes beyond simple functionality to incorporate social and psychological elements of design that promote seamless adoption by its end users. “From the start of this project, we’ve focused on understanding the real-world challenges facing these patients by visiting them in their homes to perform research,” said Walsh, an assistant professor of mechanical and biomedical engineering and founder of the Harvard Biodesign [...]

Cardiac stem cell therapy may heal heart damage caused by Duchenne muscular dystrophy

ScienceDaily, Source: Cedars-Sinai Medical Center ~ November 18, 2014 Injections of cardiac stem cells might help reverse heart damage caused by Duchenne muscular dystrophy, potentially resulting in a longer life expectancy for patients with the chronic muscle-wasting disease, researchers report. Researchers at the Cedars-Sinai Heart Institute have found that injections of cardiac stem cells might help reverse heart damage caused by Duchenne muscular dystrophy, potentially resulting in a longer life expectancy for patients with the chronic muscle-wasting disease. The study results were presented today at a Breaking Basic Science presentation during the American Heart Association Scientific Sessions in Chicago. After laboratory mice with Duchenne muscular dystrophy were infused with cardiac stem cells, the mice showed steady, marked improvement in heart function and increased exercise capacity. Duchenne muscular dystrophy, which affects 1 in 3,600 boys, is a neuromuscular disease caused by a shortage of a protein called dystrophin, leading to progressive muscle weakness. Most Duchenne patients lose their ability to walk by age 12. Average life expectancy is about 25. The cause of death often is heart failure because the dystrophin deficiency leads to cardiomyopathy, a weakness of the heart muscle that makes the heart less able to pump blood and maintain a regular rhythm. "Most research into treatments for Duchenne muscular dystrophy patients has focused on the skeletal muscle aspects of the disease, but more often than not, the cause of death has been the heart failure that affects Duchenne patients," said Eduardo Marbán, MD, PhD, director of the Cedars-Sinai Heart Institute and study leader. "Currently, there is no treatment to address the loss of functional heart muscle in these patients." During the past five years, the Cedars-Sinai Heart Institute has become a world leader [...]

After FDA Approval, Duchenne’s Muscular Dystrophy Patient Receives First Umbilical Cord Stem Cell Treatment in the United States

Virtual-Strategy Magazine, Source: PR Webb ~ September 10, 2014 Ryan Benton, a 28 year-old Duchenne’s muscular dystrophy patient from Wichita, Kansas, received his first umbilical cord tissue-derived mesenchymal stem cell treatment yesterday at Asthma and Allergy Specialists of Wichita, KS following US FDA approval of his doctor’s application for a single patient, investigational new drug (IND) for compassionate use. Ryan Benton, a 28 year-old Duchenne’s muscular dystrophy patient from Wichita, Kansas, received his first umbilical cord tissue-derived mesenchymal stem cell treatment yesterday following US FDA approval of his doctor’s application for a single patient, investigational new drug (IND) for compassionate use. Duchenne muscular dystrophy (DMD) is a rapidly progressive form of muscular dystrophy that occurs primarily in boys. It is caused by an alteration (mutation) in a gene, called the DMD gene, which causes the muscles to stop producing the protein dystrophin. Individuals who have DMD experience progressive loss of muscle function and weakness, which begins in the lower limbs and leads to progressively worsening disability. Death usually occurs by age 25, typically from lung disorders. There is no known cure for DMD. This trial, officially entitled “Allogeneic transplantation of human umbilical cord mesenchymal stem cells (UC-MSC) for a single male patient with Duchenne Muscular Dystrophy (DMD)” marks the first time the FDA has approved an investigational allogeneic stem cell treatment for Duchenne’s in the United States. Ryan received his first intramuscular stem cell injections from allergy and immunology specialist, Van Strickland, M.D at Asthma and Allergy Specialists in Wichita, Kansas. He will receive 3 more treatments this week on consecutive days. Dr. Strickland will administer similar courses to Ryan every 6 months for a total of 3 years. This is not the first time [...]