Category Archives: Genetic medicine

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.

The rest is here:
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

You may need a more recent browser or to install the latest version of the Adobe Flash Plugin.

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.

Link:
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.

Continued here:
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.'

The rest is here:
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.

See original here:
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.

Continue reading here:
Stem Cells Could Prove Effective in Treating Brittle Bone Disease

FARGO Denny Sanford was recovering from possibly fatal blood clots in his lungs when he decided to invest $125 million to bring genetic medicine into the mainstream.

Sanford became ill on a hunting trip in south-central South Dakota in October, about 140 miles west of Sioux Falls.

Doctors there suspected he had pneumonia, but Sanfords personal physician, Dr. Eric Larson of Sanford Health, suspected a pulmonary embolism a blood clot in the lungs and arranged for an air ambulance to whisk him to Sioux Falls.

He really saved my life, Sanford said in a telephone interview with The Forum, referring to Larson, an internal medicine doctor and one of the champions of the new genetic medicine initiative Sanford Health announced Tuesday.

Sanford, who is in his late 70s, did not attend Tuesdays announcement, which was made in Sioux Falls, and simulcast to Sanford medical centers in Fargo, Bismarck and Bemidji, Minn.

While recuperating in his namesake hospital in Sioux Falls, Sanford reminded Kelby Krabbenhoft, Sanford Healths top executive, that his team was preparing a genetic medicine proposal.

He invited them to make their pitch two days later, when he was convalescing at home. Sanfords recent medical emergency made him receptive to the idea of placing results of genetic testing tools in the hands of primary care physicians.

It was an opportune time to lay it out on me, Sanford said, chuckling about the timing and his gratitude for the care he received.

I believe that is the medicine of the future, added Sanford, referring to the use of genetic information in tailoring health care. He recently donated $100 million to a stem cell research program in California.

Sanford, a St. Paul native who founded Premier Bank, now has donated more than $1 billion, much of it to Sanford Health, beginning with a $400 million gift in 2007.

Link:
Denny Sanford believes genetic medicine is 'the medicine of the future'

Public release date: 29-Nov-2012 [ | E-mail | Share ]

Contact: Lauren Woods Law2014@med.cornell.edu 646-317-7401 New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

NEW YORK (Nov. 29, 2012) -- Weill Cornell Medical College researchers Dr. Shahin Rafii and Dr. Xin-Yun Huang have been elected new Fellows of the American Association for the Advancement of Science (AAAS), the world's largest general scientific society, for their significant contributions to the advancement of the biological sciences.

Dr. Rafii, director of the Ansary Stem Cell Institute and the Arthur B. Belfer Professor in Genetic Medicine at Weill Cornell, is honored for his important contributions to the field of vascular biology, stem cell homeostasis and the development of transformative preclinical models to induce organ regeneration and target tumors. Dr. Huang, professor of physiology and biophysics at Weill Cornell, is recognized for his distinguished contributions in the field of cellular signaling, particularly his investigations of G-protein-mediated cell signaling.

"Dr. Rafii and Dr. Huang's research discoveries in cellular communication, stem cell research, cancer and vascular disease have led to major advancements in biomedical research and the development of targeted therapies," says Dr. Laurie H. Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College, who is also a Fellow of AAAS. "Weill Cornell is very proud of the work of these two world-renowned innovators in medicine and their new membership in this prominent community of scientists dedicated to advancing science around the world."

This year, Dr. Rafii and Dr. Huang are among the 702 new Fellows awarded election to the AAAS for their scientifically or socially-distinguished efforts to advance science or its applications. This prestigious honor of AAAS election is bestowed by peer Fellows of AAAS.

Dr. Rafii and Dr. Huang will be presented with an official certificate and a gold and blue rosette pin, representing science and engineering, on Saturday, Feb. 16 at the AAAS Fellows Forum during the 2013 AAAS Annual Meeting in Boston, MA. Also, new AAAS Fellows will be announced in the AAAS' journal Science on Nov. 30.

Dr. Rafii, an internationally known vascular biologist, cancer and stem-cell authority, is also an investigator of Howard Hughes Medical Institute at Weill Cornell. Dr. Rafii's research explores innovative therapeutic frontiers for cancer and vascular disorders. His research focuses on the understanding of stem cell biology, as well as the means to develop and test innovative approaches to treat cancer and vascular disorders by exploring the therapeutic potential of human and embryonic stem cells and, most recently, amniotic-fluid derived cells for treatment of human malignancies, vascular diseases and genetic disorders. His work has paved the way for stem-cell therapy for the treatment of vascular insufficiencies. Dr. Rafii received his undergraduate degree in chemistry from Cornell University and his medical degree from Albert Einstein College of Medicine. He has been funded by multiple grants from the National Institute of Health's Heart, Lung and Blood Institute, and is an active member of the Tumor Microenvironment Study Section at the National Cancer Institute. He is an elected member of the American Society of Clinical Investigation, an American Cancer Society Scholar and a Translational Researcher of the Leukemia & Lymphoma Society.

Dr. Huang's research focuses on G protein-coupled receptors and G proteins that are key cell signaling molecules with the ability to control and disseminate information flow. G protein-coupled receptors represent approximately 40 percent of the current drug targets. These receptors are activated by a diverse array of ligands, including photons, odorants, chemokines, hormones, growth factors and neurotransmitters. The GPCR-G protein signaling system plays critical roles in various physiological functions such as cardiovascular and neurological functions, and in human diseases such as cancer. Dr. Huang examines signal transduction using biochemical, genetic, molecular, cellular and structural biological approaches to uncover fundamental mechanisms that govern cellular signaling and physiological functions. His team inspects cross-talk between G proteins and nonreceptor tyrosine kinases, two of the most widely used cellular signaling mechanisms. Dr. Huang explores the activation mechanisms of G proteins by G protein-coupled receptors, the regulatory mechanisms of endothelial cell migration, blood vessel formation and tumor angiogenesis by G proteins, as well as the control mechanisms for actin cytoskeletal reorganization, cell migration and tumor metastasis. Dr. Huang completed his undergraduate studies at Wuhan University in China, received his Ph.D. from the University of Houston and his postdoctoral research training at Columbia University and Harvard University.

The AAAS Fellows tradition began in 1874. Currently, members can be considered for the rank of Fellow if nominated by the steering groups of the Association's 24 sections, or by any three Fellows who are current AAAS members, or by the AAAS chief executive officer. Each steering group then reviews the nominations of individuals within its respective section and a final list is forwarded to the AAAS Council, which votes on the aggregate list. The Council is the policymaking body of the Association, chaired by the AAAS president, and consisting of the members of the board of directors, the retiring section chairs, delegates from each electorate and each regional division and two delegates from the National Association of Academies of Science.

See more here:
Weill Cornell researchers elected Fellows of AAAS

Newswise LOS ANGELES (June 19, 2012) Cedars-Sinais Regenerative Medicine Institute has pioneered research on how motor-neuron cell-death occurs in patients with spinal muscular atrophy, offering an important clue in identifying potential medicines to treat this leading genetic cause of death in infants and toddlers.

The study, published in the June 19 online issue of PLoS ONE, extends the institutes work to employ pluripotent stem cells to find a pharmaceutical treatment for spinal muscular atrophy or SMA, a genetic neuromuscular disease characterized by muscle atrophy and weakness.

With this new understanding of how motor neurons die in spinal muscular atrophy patients, we are an important step closer to identifying drugs that may reverse or prevent that process, said Clive Svendsen, PhD, director of the Cedars-Sinai Regenerative Medicine Institute.

Svendsen and his team have investigated this disease for some time now. In 2009, Nature published a study by Svendsen and his colleagues detailing how skin cells taken from a patient with the disorder were used to generate neurons of the same genetic makeup and characteristics of those affected in the disorder; this created a disease-in-a-dish that could serve as a model for discovering new drugs.

As the disease is unique to humans, previous methods to employ this approach had been unreliable in predicting how it occurs in humans. In the research published in PLoS ONE, to the team reproduced this model with skin cells from multiple patients, taking them back in time to a pluripotent stem cell state (iPS cells), and then driving them forward to study the diseased patient-specific motor neurons.

Children born with this disorder have a genetic mutation that doesnt allow their motor neurons to manufacture a critical protein necessary for them to survive. The study found these cells die through apoptosis the same form of cell death that occurs when the body eliminates old, unnecessary as well as unhealthy cells. As motor neuron cell death progresses, children with the disease experience increasing paralysis and eventually death. There is no effective treatment now for this disease. An estimated one in 35 to one in 60 people are carriers and about in 100,000 newborns have the condition.

Now we are taking these motor neurons (from multiple children with the disease and in their pluripotent state) and screening compounds that can rescue these cells and create the protein necessary for them to survive, said Dhruv Sareen, director of Cedars-Sinais Induced Pluripotent Stem Cell Core Facility and a primary author on the study. This study is an important stepping stone to guide us toward the right kinds of compounds that we hope will be effective in the model and then be reproduced in clinical trials.

The study was funded in part by a $1.9 million Tools and Technology grant from the California Institute for Regenerative Medicine aimed at developing new tools and technologies to aid pharmaceutical discoveries for this disease.

# # #

Continue reading here:
Researchers, with Stem Cells, Advance Understanding of Spinal Muscular Atrophy

Public release date: 19-Jun-2012 [ | E-mail | Share ]

Contact: Nicole White nicole.white@cshs.org 310-423-5215 Cedars-Sinai Medical Center

LOS ANGELES (June 19, 2012) Cedars-Sinai's Regenerative Medicine Institute has pioneered research on how motor-neuron cell-death occurs in patients with spinal muscular atrophy, offering an important clue in identifying potential medicines to treat this leading genetic cause of death in infants and toddlers.

The study, published in the June 19 online issue of PLoS ONE, extends the institute's work to employ pluripotent stem cells to find a pharmaceutical treatment for spinal muscular atrophy or SMA, a genetic neuromuscular disease characterized by muscle atrophy and weakness.

"With this new understanding of how motor neurons die in spinal muscular atrophy patients, we are an important step closer to identifying drugs that may reverse or prevent that process," said Clive Svendsen, PhD, director of the Cedars-Sinai Regenerative Medicine Institute.

Svendsen and his team have investigated this disease for some time now. In 2009, Nature published a study by Svendsen and his colleagues detailing how skin cells taken from a patient with the disorder were used to generate neurons of the same genetic makeup and characteristics of those affected in the disorder; this created a "disease-in-a-dish" that could serve as a model for discovering new drugs.

As the disease is unique to humans, previous methods to employ this approach had been unreliable in predicting how it occurs in humans. In the research published in PLoS ONE, to the team reproduced this model with skin cells from multiple patients, taking them back in time to a pluripotent stem cell state (iPS cells), and then driving them forward to study the diseased patient-specific motor neurons.

Children born with this disorder have a genetic mutation that doesn't allow their motor neurons to manufacture a critical protein necessary for them to survive. The study found these cells die through apoptosis the same form of cell death that occurs when the body eliminates old, unnecessary as well as unhealthy cells. As motor neuron cell death progresses, children with the disease experience increasing paralysis and eventually death. There is no effective treatment now for this disease. An estimated one in 35 to one in 60 people are carriers and about in 100,000 newborns have the condition.

"Now we are taking these motor neurons (from multiple children with the disease and in their pluripotent state) and screening compounds that can rescue these cells and create the protein necessary for them to survive," said Dhruv Sareen, director of Cedars-Sinai's Induced Pluripotent Stem Cell Core Facility and a primary author on the study. "This study is an important stepping stone to guide us toward the right kinds of compounds that we hope will be effective in the model and then be reproduced in clinical trials."

###

Read the original here:
Cedars-Sinai researchers, with stem cells, advance understanding of spinal muscular atrophy