Category Archives: Genetic medicine

PUBLIC RELEASE DATE:

24-Sep-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center @sumedicine

Over 500 million people worldwide carry a genetic mutation that disables a common metabolic protein called ALDH2. The mutation, which predominantly occurs in people of East Asian descent, leads to an increased risk of heart disease and poorer outcomes after a heart attack. It also causes facial flushing when carriers drink alcohol.

Now researchers at the Stanford University School of Medicine have learned for the first time specifically how the mutation affects heart health. They did so by comparing heart muscle cells made from induced pluripotent stem cells, or iPS cells, from people with the mutation versus those without the mutation. IPS cells are created in the laboratory from specialized adult cells like skin. They are "pluripotent," meaning they can be coaxed to become any cell in the body.

"This study is one of the first to show that we can use iPS cells to study ethnic-specific differences among populations," said Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute and professor of cardiovascular medicine and of radiology.

"These findings may help us discover new therapeutic paths for heart disease for carriers of this mutation," said Wu. "In the future, I believe we will have banks of iPS cells generated from many different ethnic groups. Drug companies or clinicians can then compare how members of different ethnic groups respond to drugs or diseases, or study how one group might differ from another, or tailor specific drugs to fit particular groups."

The findings are described in a paper that will be published Sept. 24 in Science Translational Medicine. Wu and Daria Mochly-Rosen, PhD, professor of chemical and systems biology, are co-senior authors of the paper, and postdoctoral scholar Antje Ebert, PhD, is the lead author.

ALDH2 and cell death

The study showed that the ALDH2 mutation affects heart health by controlling the survival decisions cells make during times of stress. It is the first time ALDH2, which is involved in many common metabolic processes in cells of all types, has been shown to play a role in cell survival. In particular, ALDH2 activity, or the lack of it, influences whether a cell enters a state of programmed cell death called apoptosis in response to stressful growing conditions.

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Stanford scientists use stem cells to learn how common mutation in Asians affects heart health

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Newswise LOS ANGELES (July 24, 2014) Like other major research centers studying genetic causes of uncommon and poorly understood nervous system disorders, Cedars-Sinai maintains a growing collection of DNA and tissue samples donated by patients.

What sets Cedars-Sinais Repository of Neurologic and Neuromuscular Disorders apart is its special emphasis on tissue collection part of its focus on creating future individualized treatments for patients.

One of our major priorities is to advance the concept of personalized medicine. The idea is to take DNA from a patient, look at the cells derived from their tissue, and try to understand why this particular person got this disease. Then we can determine which therapy or therapies would work for each individual by first testing their cells. Many centers look at the genetics; ours is dedicated to looking at the genetics and the patients tissues, combining the two to understand how to treat the disease, said Robert H. Baloh, MD, PhD, director of neuromuscular medicine in the Department of Neurology and director of the ALS Program for research and treatment of amyotrophic lateral sclerosis, or Lou Gehrigs disease.

This individualized treatment approach depends on collaborative efforts among doctors and researchers who treat and study individual diseases and scientists at the Cedars-Sinai Regenerative Medicine Institute, one of a very few hospital-based centers devoted to stem cell research. The teams work together to discover disease-generating molecular and cellular defects, make disease-in-a-dish models and begin to fashion personalized stem cell-based research interventions.

We know that nearly every disease has some genetic component some more than others so we collect DNA for research to identify those genetic elements. But weve also expanded our focus to include the collection of skin and blood samples that can be turned into specialized stem cells. Patients are usually very willing to donate tissue to try and help us understand the causes of their neurologic or neuromuscular disease, said Baloh, a member of the Brain Program at the Regenerative Medicine Institute.

Baloh and colleagues recently showed this approach is feasible, using skin biopsies from patients with ALS. With induced pluripotent stem cells, or iPSCs, they created ALS neurons in a lab dish. Then, inserting molecules made of small stretches of genetic material, they blocked the damaging effects of a defective gene. This provided proof of concept for a new therapeutic strategy an important step in moving research findings into clinical trials.

Baloh, the repositorys principal investigator, has a particular interest in ALS and other neuromuscular disorders, but DNA, tissue and data collection is conducted for Cedars-Sinai neuroscience researchers studying virtually any disease. And its holdings can have widespread influence: Repositories of genetic material enable scientists studying similar diseases at multiple research centers to access patient data in larger quantities than any single site could provide.

We work with many other research institutions across the country to share the samples themselves as well as de-identified information about the patients what disease they have, the severity of their disease, and similar disorder-related details. This improves our ability to find new gene abnormalities, because it cant always be done with just tens or even hundreds of patients. We may need thousands of patients, especially for very rare genetic forms of disease that have very subtle genetic effects. Therefore, we study our own patients in great detail, but we also share our resources more broadly, said Baloh, adding that genetic discoveries often have implications even for patients who dont have genetic forms of disease.

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Tissue Collection Aids Search for Neurologic and Neuromuscular Disease Causes and Cures

PUBLIC RELEASE DATE:

18-Jul-2014

Contact: Charles Casey charles.casey@ucdmc.ucdavis.edu 916-734-9048 University of California - Davis Health System

(SACRAMENTO, Calif.) Researchers from UC Davis School of Medicine and Shriners Hospitals for Children Northern California have identified a group of cells in the brain that they say plays an important role in the abnormal neuron development in Down syndrome. After developing a new model for studying the syndrome using patient-derived stem cells, the scientists also found that applying an inexpensive antibiotic to the cells appears to correct many abnormalities in the interaction between the cells and developing neurons.

The findings, which focused on support cells in the brain called astroglial cells, appear online today in Nature Communications.

"We have developed a human cellular model for studying brain development in Down syndrome that allows us to carry out detailed physiological studies and screen possible new therapies," said Wenbin Deng, associate professor of biochemistry and molecular medicine and principal investigator of the study. "This model is more realistic than traditional animal models because it is derived from a patient's own cells."

Down syndrome is the most common chromosomal cause of mild to moderate intellectual disabilities in the United States, where it occurs in one in every 691 live births. It develops when a person has three copies of the 21st chromosome instead of the normal two. While mouse models have traditionally been used in studying the genetic disorder, Deng said the animal model is inadequate because the human brain is more complicated, and much of that complexity arises from astroglia cells, the star-shaped cells that play an important role in the physical structure of the brain as well as in the transmission of nerve impulses.

"Although neurons are regarded as our 'thinking cells,' the astroglia have an extremely important supportive role," said Deng. "Astroglial function is increasingly recognized as a critical factor in neuronal dysfunction in the brain, and this is the first study to show its importance in Down syndrome."

Creating a unique human cellular model

To investigate the role of astroglia in Down syndrome, the research team took skin cells from individuals with Down syndrome and transformed them into stem cells, which are known as induced pluripotent stem cells (iPSC). The cells possess the same genetic make-up as the donor and an ability to grow into different cell types. Deng and his colleagues next induced the stem cells to develop into separate pure populations of astroglial cells and neurons. This allowed them to systematically analyze factors expressed by the astroglia and then study their effects on neuron development.

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'Support' cells in brain play important role in Down syndrome

PUBLIC RELEASE DATE:

17-Jul-2014

Contact: Jeannette Spalding jeannette.spalding@case.edu 216-368-3004 Case Western Reserve University

The mysterious condition once known as "water on the brain" became just a bit less murky this week thanks to a global research group led in part by a Case Western Reserve researcher. Professor Anthony Wynshaw-Boris, MD, PhD, is the co-principal investigator on a study that illustrates how the domino effect of one genetic error can contribute to excessive cerebrospinal fluid surrounding the brains of mice a disorder known as hydrocephalus. The findings appear online July 17 in the journal Neuron.

Cerebrospinal fluid provides a cushion between the organ and the skull, eliminating waste and performing other functions essential to neurological health. Within the brain there are four spaces or ventricles where cerebrospinal fluid flows. Hydrocephalus can be damaging when excessive cerebrospinal fluid widens spaces between ventricles and creates pressure to brain tissue. In humans, hydrocephalus can cause a host of neurological ailments: impairment of balance and coordination, memory loss, headaches and blurred vision, and even damage to the brain.

"Most of the time, hydrocephalus is caused by some sort of physical blockage of the flow of cerebrospinal fluid, so called obstructive hydrocephalus. We demonstrated instead that malfunction of specific genes the Dishevelleds (Dvl genes) triggered hydrocephalus in our mouse models. These genes regulate the precise placement and alignment of cilia within ependymal cells that move cerebrospinal fluid throughout the brain," said Wynshaw-Boris, MD, PhD, James H. Jewell MD '34 Professor of Genetics and Chair, Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine. "This discovery paves the way for more focused research to determine if similar mechanisms can cause hydrocephalus in humans."

Scientists are still at the most nascent stages of understanding different causes and kinds of hydrocephalus. In some instances, the root sources are genetic; in others, the fluid accumulation is attributed to complications of premature birth. This project illuminates one way in which genetic influences contribute to the condition.

Wynshaw-Boris began this collaborative research while a professor in pediatrics at the Institute for Human Genetics and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California at San Francisco (UCSF) before coming to Case Western Reserve in June 2013. For this hydrocephalus project, he joined fellow principal co-investigator, Arturo Alvarez-Buylla, PhD, professor of neurological surgery, and the Heather and Melanie Muss Endowed Chair, Department of Neurological Surgery, UCSF, in conducting research that proved in mice that Dvl genes regulate the placement and polarity of cilia in ependymal cells that line the ventricles of the brain.

A cilium is a slender protuberance projecting from many cells. In the ependymal cells, multiple cilia protrude from each cell as a bundle or patch, which resembles a horse's tail when beating to move cerebrospinal fluid efficiently. Each cilium must be anchored, sized and shaped correctly, properly placed and aligned in relation to other cilia within the same cell, and the alignment of cilia between cells is also necessary so that the cilia beat with precision to achieve proper movement of fluid in the right direction. It is all about excellent organization: the wrong size, shape or angle of rotation of the bundle of cilia will impede the smooth and appropriate directional flow of the cerebrospinal fluid.

The work in mice by Shinya Ohata, PhD, and Jin Nakatani, PhD, co-first authors who worked in the Alvarez-Buylla and Wynshaw-Boris labs, respectively, and their colleagues demonstrated how normal versus Dvl-deficient mice fared in terms of cilia function. They examined cilia from the ependymal cells of normal mice and found the cilia to be well organized and correctly placed within and between ependymal cells. Investigators even viewed in real time through fluorescent imaging the intricacy with which well-orchestrated cilia swayed to move fluid along in a normal fashion.

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International research team discovers genetic dysfunction connected to hydrocephalus

PUBLIC RELEASE DATE:

3-Jul-2014

Contact: Shawna Williams shawna@jhmi.edu 410-955-8236 Johns Hopkins Medicine

Johns Hopkins researchers have begun to connect the dots between a schizophrenia-linked genetic variation and its effect on the developing brain. As they report July 3 in the journal Cell Stem Cell, their experiments show that the loss of a particular gene alters the skeletons of developing brain cells, which in turn disrupts the orderly layers those cells would normally form.

"This is an important step toward understanding what physically happens in the developing brain that puts people at risk of schizophrenia," says Guo-li Ming, M.D., Ph.D., a professor of neurology and neuroscience in the Johns Hopkins University School of Medicine's Institute for Cell Engineering.

While no single genetic mutation is known to cause schizophrenia, so-called genomewide association studies have identified variations that are more common in people with the condition than in the general population. One of these is a missing piece from an area of the genome labeled 15q11.2. "While the deletion is linked to schizophrenia, having extra copies of this part of the genome raises the risk of autism," notes Ming.

For the new study, Ming's research group, along with that of her husband and collaborator, neurology and neuroscience professor Hongjun Song, Ph.D., used skin cells from people with schizophrenia who were missing part of 15q11.2 on one of their chromosomes. (Because everyone carries two copies of their genome, the patients each had an intact copy of 15q11.2 as well.)

The researchers grew the human skin cells in a dish and coaxed them to become induced pluripotent stem cells, and then to form neural progenitor cells, a kind of stem cell found in the developing brain.

"Normally, neural progenitors will form orderly rings when grown in a dish, but those with the deletion didn't," Ming says. To find out which of the four known genes in the missing piece of the genome were responsible for the change, the researchers engineered groups of progenitors that each produced less protein than normal from one of the suspect genes. The crucial ingredient in ring formation turned out to be a gene called CYFIP1.

The team then altered the genomes of neural progenitors in mouse embryos so that they made less of the protein created by CYFIP1. The brain cells of the fetal mice turned out to have similar defects in structure to those in the dish-grown human cells. The reason, the team found, is that CYFIP1 plays a role in building the skeleton that gives shape to each cell, and its loss affects spots called adherens junctions where the skeletons of two neighboring cells connect.

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Schizophrenia-associated gene variation affects brain cell development

Illlustration by Vasava

Douglass Turnbull spends much of his time seeing patients who have untreatable, often fatal, diseases. But the neurologist has rarely felt more helpless than when he met Sharon Bernardi and her young son Edward.

Bernardi had lost three children within hours of birth, owing to a mysterious build-up of acid in their blood. So it was a huge relief when Edward seemed to develop normally. He did all his milestones: he sat up, he crawled and started to walk at 14 months, Bernardi recalls. But when he was about two years old, he began to fall over after taking a few steps; he eventually started having seizures. In 1994, when Edward was four, he was diagnosed with Leigh's disease, a condition that affects the central nervous system. Doctors told Sharon that her son would be lucky to reach his fifth birthday.

Turnbull, who works at Newcastle University, UK, remembers despairing that whatever we do, we're never going to be able to help families like that. His frustration sparked a quest to develop assisted-reproduction techniques to prevent disorders such as Leigh's disease, which are caused when children inherit devastating mutations in their mitochondria, the cell's energy-making structures.

The procedures sometimes called three-person in vitro fertilization (IVF) involve transferring nuclear genetic material from the egg of a woman with mutant mitochondria into another woman's healthy egg. Turnbull and others have tested the techniques in mice, monkeys and human egg cells in culture; now, they say, it is time to try them in people. The UK Parliament is set to vote on the issue later this year; if legislation passes, the country would be the first to allow this kind of genetic modification of unborn children.

Ewen Callaway talks to researchers and a patient about the techniques that replace faulty DNA in egg cells

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But some scientists have raised concerns over the safety of the procedures, and an increasingly vocal coalition of activists, ethicists and politicians argues that a 'yes' vote will lead down a slippery slope to designer babies. US regulators and scientists are closely watching the debate as they consider allowing similar procedures. I admire what they've done in Britain, says Dieter Egli, a stem-cell scientist at the New York Stem Cell Foundation, a non-profit research institute. I think they are far ahead in discussion of this, compared to the US.

The mitochondrion, according to one popular theory, was once a free-living bacterium that became trapped in a host cell, where it boosted the cell's capacity to generate the energy-carrying molecule ATP. As a result, each mitochondrion has its own genome but it no longer has all the genes it needs to function independently (the human mitochondrial genome, for example, has a paltry 37 genes).

Unlike the genome in the cell nucleus, which includes chromosomes from both parents, all of a person's mitochondria derive from the thousands contained in the mother's egg. For reasons still being studied, the mitochondrial genome is much less stable than the nuclear genome, accruing random DNA mutations about 1,000 times faster. As many as 1 in 5,000 children are born with diseases caused by these mutations, which affect power-hungry cells such as those in the brain and muscles. The severity of the conditions depends on the proportion of diseased mitochondria a mother passes on to her children.

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Reproductive medicine: The power of three

Meeri N. Kim, For The Inquirer Last updated: Sunday, May 18, 2014, 8:51 AM Posted: Saturday, May 17, 2014, 3:55 PM

Imagine a document 25,000 words long - about 100 pages, double-spaced - with one small error. Within the text of our genetic code, a single change like this can lead to a life-threatening disease such as sickle-cell anemia or cystic fibrosis.

Most of these single-gene disorders have no cure. But using a new technique, doctors may one day be able to correct the genetic typo by replacing a harmful mutation in the genome with healthy DNA.

Introducing CRISPR (clustered regularly interspaced short palindromic repeats), a genetic editing tool that can cut and paste parts of any living animal's DNA. Although in its infancy, the system is generating excitement among scientists for its ease of use, accessibility, and vast potential.

The CRISPR system enables researchers to make a small chain of custom-made molecules, called a guide RNA, and a Cas9 enzyme. The guide RNA is like the search function of a word processor, running along the length of the genome until it finds a match; then, the scissorslike Cas9 cuts the DNA. CRISPR can be used to delete, insert, or replace genes.

"We didn't used to think that we had the tools to correct mutation in humans," said Penn Medicine cardiologist Jonathan Epstein, who just began using the technique in his lab. "The advantage of CRISPR is that we can."

For instance, sickle-cell anemia is caused by a mutation in chromosome 11 that causes red blood cells to be crescent-shaped, sticky, and stiff. They end up stuck in the blood vessels, keeping enough oxygen from reaching the body. While the disease can be treated with bone marrow or stem cell transplants, most patients cannot find well-matched donors.

Here's where CRISPR can help. Biomedical engineer Gang Bao of the Georgia Institute of Technology aims to use the system to repair the DNA of a patient's own stem cells, so no outside donor would be needed. The stem cells would be extracted from the patient's bone marrow, their mutations replaced with normal DNA, and inserted back in. The hope is that the gene-corrected stem cells would then begin making normal red blood cells.

The treatment works in mice, and Bao foresees human trials within a few years.

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Genetic 'typo' corrector

The gene mutations driving cancer have been tracked for the first time in patients back to a distinct set of cells at the root of cancer -- cancer stem cells.

The international research team, led by scientists at the University of Oxford and the Karolinska Institutet in Sweden, studied a group of patients with myelodysplastic syndromes -- a malignant blood condition which frequently develops into acute myeloid leukaemia.

The researchers say their findings, reported in the journal Cancer Cell, offer conclusive evidence for the existence of cancer stem cells.

The concept of cancer stem cells has been a compelling but controversial idea for many years. It suggests that at the root of any cancer there is a small subset of cancer cells that are solely responsible for driving the growth and evolution of a patient's cancer. These cancer stem cells replenish themselves and produce the other types of cancer cells, as normal stem cells produce other normal tissues.

The concept is important, because it suggests that only by developing treatments that get rid of the cancer stem cells will you be able to eradicate the cancer. Likewise, if you could selectively eliminate these cancer stem cells, the other remaining cancer cells would not be able to sustain the cancer.

'It's like having dandelions in your lawn. You can pull out as many as you want, but if you don't get the roots they'll come back,' explains first author Dr Petter Woll of the MRC Weatherall Institute for Molecular Medicine at the University of Oxford.

The researchers, led by Professor Sten Eirik W Jacobsen at the MRC Molecular Haematology Unit and the Weatherall Institute for Molecular Medicine at the University of Oxford, investigated malignant cells in the bone marrow of patients with myelodysplastic syndrome (MDS) and followed them over time.

Using genetic tools to establish in which cells cancer-driving mutations originated and then propagated into other cancer cells, they demonstrated that a distinct and rare subset of MDS cells showed all the hallmarks of cancer stem cells, and that no other malignant MDS cells were able to propagate the tumour.

The MDS stem cells were rare, sat at the top of a hierarchy of MDS cells, could sustain themselves, replenish the other MDS cells, and were the origin of all stable DNA changes and mutations that drove the progression of the disease.

'This is conclusive evidence for the existence of cancer stem cells in myelodysplastic syndromes,' says Dr Woll. 'We have identified a subset of cancer cells, shown that these rare cells are invariably the cells in which the cancer originates, and also are the only cancer-propagating cells in the patients. It is a vitally important step because it suggests that if you want to cure patients, you would need to target and remove these cells at the root of the cancer -- but that would be sufficient, that would do it.'

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Genetic tracking identifies cancer stem cells in human patients

Microarray analysis -- a complex technology commonly used in many applications such as discovering genes, disease diagnosis, drug development and toxicological research -- has just become easier and more user-friendly. A new advanced software program called Eureka-DMA provides a cost-free, graphical interface that allows bioinformaticians and bench-biologists alike to initiate analyses, and to investigate the data produced by microarrays. The program was developed by Ph.D. student Sagi Abelson of the Rappaport Faculty of Medicine at the Technion-Israel Institute of Technology in Haifa, Israel.

DNA microarray analysis, a high-speed method by which the expression of thousands of genes can be analyzed simultaneously, was invented in the late 1980s and developed in the 1990s. Genetic researchers used a glass slide with tiny dots of copies of DNA to test match genes they were trying to identify. Because the array of dots was so small, it was called a "microarray." There is a strong correlation between the field of molecular biology and medical research, and microarray technology is used routinely in the area of cancer research and other epidemiology studies. Many research groups apply it to detect genetic variations between biological samples and information about aberrant gene expression levels can be used in what is called "personalized medicine." This includes customized approaches to medical care, including finding new drugs for gene targets where diseases have genetic causes and potential cures are based on an individual's aberrant gene's signal.

An article written by Abelson published in the current issue of BMC Bioinformatics (2014,15:53) describes the new software tool and provides examples of its uses.

"Eureka-DMA combines simplicity of operation and ease of data management with the rapid execution of multiple task analyses," says Abelson. "This ability can help researchers who have less experience in bioinformatics to transform the high throughput data they generate into meaningful and understandable information."

Eureka-DMA has a distinct advantage over other software programs that only work "behind the scenes" and provide only a final output. It provides users with an understanding of how their actions influence the outcome throughout all the data elucidation steps, keeping them connected to the data, and enabling them to reach optimal conclusions.

"It is very gratifying to see the insightful initiative of Sagi Abelson, a leading 'out-of-the-box' thoughtful Technion doctorate student whom I have had the privilege of supervising," said Prof. Karl Skorecki, the Director of the Rappaport Family Institute for Research in the Medical Sciences at the Technion Faculty of Medicine and Director of Medical and Research Development at the Rambam Health Care Campus. "Over and above his outstanding PhD thesis research project on cancer stem cells, Sagi has developed -- on his own -- a user-friendly computer-based graphical interface for health and biological research studies. Eureka-DMA enables users to easily interpret massive DNA expression data outputs, empowering researchers (and in the future, clinicians) to generate new testable hypotheses with great intuitive ease, and to examine complex genetic expression signatures of genes that provide information relevant to health and disease conditions. This was enabled by combining outstanding insight and expertise in biological and computer sciences, demonstrating the unique multidisciplinary strengths and intellectual freedom that fosters creative innovation at the Technion."

According to Abelson, Eureka-DMA was programmed in MATLAB, a high-level language and interactive environment for numerical computation, visualization, and programming. Advanced users of MATLAB can analyze data, develop algorithms, and create models and applications to explore multiple hypotheses and reach solutions faster than with spreadsheets or traditional software. Eureka-DMA uses many of MATLAB's toolbox features to provide ways to search for enriched pathways and genetic terms and then combines them with other relevant features.

Raw data input is through Windows Excel or text files. This, says Abelson, spares the user from dealing with multiple and less common microarray files received by different manufacturers. Results can then be exported into a 'txt' file format,' or Windows Excel, making Eureka-DMA a unified and flexible platform for microarray data analysis, interpretation and visualization. It can also be used as a fast validation tool for results obtained by different methods.

Eureka-DMA loads and exports genetic data, "normalizes" raw data, filters non-relevant data, and enables pathway enrichment analysis for mapping genes on cellular pathways. The user can browse through the enriched pathways and create an illustration of the pathway with the differentially expressed genes highlighted.

After identifying the differentially expressed genes, biological meaning is ascribed via the software so that the identification of significant co-clustered genes with similar properties -- cellular components, a biological process, or a molecular function -- can be achieved.

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Free online software helps speed up genetic discoveries

Durham, NC (PRWEB) January 14, 2014

A new study released in STEM CELLS Translational Medicine indicates that stem cells can be effective in treating a debilitating and sometimes lethal genetic disorder called brittle bone disease.

Brittle bone disease, or osteogenesis imperfecta (OI), is characterized by fragile bones causing some patients to suffer hundreds of fractures over the course of a lifetime. In addition, according to the OI Foundation, other symptoms include muscle weakness, hearing loss, fatigue, joint laxity, curved bones, scoliosis, brittle teeth and short stature. Restrictive pulmonary disease occurs in the more severe cases. Currently there is no cure.

OI can be detected prenatally by ultrasound. In the study reported on in STEM CELLS Translational Medicine, an international team of researchers treated two patients for the disease using mesenchymal stem cells (MSCs) while the infants were still in the womb, followed by stem cell boosts after they were born.

We had previously reported on the prenatal transplantation for the patient with OI type III, which is the most severe form in children who survive the neonatal period, said Cecilia Gtherstrm, Ph.D., of the Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. She and Jerry Chan, M.D., Ph.D., of the Yong Loo Lin School of Medicine and National University of Singapore, and KK Womens and Childrens Hospital, led the study that also included colleagues from the United States, Canada, Taiwan and Australia.

The first eight years after the prenatal transplant, our patient did well and grew at an acceptable rate. However, she then began to experience multiple complications, including fractures, scoliosis and reduction in growth, so the decision was made to give her another MSC infusion. In the two years since, she has not suffered any more fractures and improved her growth.

She was even able to start dance classes, increase her participation in gymnastics at school and play modified indoor hockey, Dr. Gtherstrm added.

The second child, which was experiencing a milder form of OI, received a stem cell transfusion 31 weeks into gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. She followed her normal growth pattern just under the third percentile in height until 13 months of age, when she stopped growing. Six months later, the doctors gave her another infusion of stem cells and she resumed growing at her previous rate.

Our findings suggest that prenatal transplantation of autologous stem cells in OI appears safe and is of likely clinical benefit and that re-transplantation with same-donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive, for which further studies are required, Dr. Chan said.

Although the findings are preliminary, this report is encouraging in suggesting that prenatal transplantation may be a safe and effective treatment for this condition, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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Stem Cells Could Prove Effective in Treating Brittle Bone Disease