Category Archives: Gene Medicine

Stem Cell Therapy for Sickle Cell Anemia
CIRM has funded a $9 million disease team to develop a more effective and safer bone marrow transplant to treat sickle cell disease. The team is led by Dr. Donald Kohn, director of the Human Gene Medicine Program at UCLA. Kohn updated the CIRM Governing Board on May 05, 2011 about his team #39;s progress. Nancy Rene, a patient advocate for the Sickle Cell Foundation of California, also spoke to the board. Through photos and stories, Rene described the impact of sickle cell anemia on her grandson #39;s life. She also spoke about the importance of support services for sickle cell patients and continued research for a cure. Series: "California Institute for Regenerative Medicine" [Health and Medicine] [Show ID: 22634]From:UCtelevisionViews:1065 4ratingsTime:58:14More inEducation

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Stem Cell Therapy for Sickle Cell Anemia - Video

Published: Oct. 16, 2012 at 8:30 PM

EVANSTON, Ill., Oct. 16 (UPI) -- U.S. scientists say they've discovered how to control the shape of nanoparticles that can move DNA through the body to treat cancer and other diseases.

A gene therapy technique utilizing nanoparticles is significant in that it does not use a virus to carry DNA into cells, as some gene therapy strategies relying on viruses have posed health risks, researchers at Northwestern University and John Hopkins University reported.

"These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine," John Hopkins material science Professor Hai-Quan Mao said.

Mao, who has been developing non-viral nanoparticles for gene therapy for a decade, said a major breakthrough is the ability to "tune" the particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles.

The nanoparticles carry healthy snippets of DNA within protective polymer coatings and are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells, prompting the cells to produce functional proteins that combat disease.

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Nanoparticles seen as gene therapy advance

Reported by Julielynn Wong, MD

A single gene may shed light on why more than half of transplanted kidneys fail in 10 years, a new study found.

The study of nearly 4,500 European transplant recipients, some whom were followed for 20 years, found kidneys with one version of the gene were 69 percent more likely to fail, sending patients back to dialysis and a transplant waiting list.

But with a wait list 74,000 names long and only17,500 kidneys donated annually, doctors wont be excluding any organs based on the gene variant just yet.

We just dont have enough donor kidneysto go around now, said Dr. Michael E. Shapiro, associate professor of surgery at New Jersey Medical School/University of Medicine and Dentistry New Jersey, who was not involved in the study. So wecouldntexclude such kidneys based solely on genetic variation.

The study authors are unsure why the gene variant is linked to a higher risk of kidney failure after a transplant, but they suspect it might have to do with the anti-rejection drugs needed to prevent the immune system from attacking the new organ. Those drugs can cause kidney failure if they accumulate in high levels, they said.

But because kidneys are such a rare and valuable resource, even those more likely to fail in the long run will continue to be transplanted. The alternative is dialysis, a process that artificially filters blood, according to Dr. Stanley Jordan, medical director of the Kidney Transplant Program at Cedars-Sinai Medical Center in Los Angeles, who was not involved with the study.

And dialysis has its drawbacks.

We know that remaining on dialysis has a very high mortality rate, as high as 20 percent per year for some patients, said Jordan.

Dialysis costs roughly $85,000 per year, compared with $19,000 per year for a working transplanted kidney, Jordan said, citing a 2011 report on the United States Renal Data System website. But the cost of treating a failed kidney transplant can be as high as $230,000 in the first year, with Medicare usually bearing the brunt of these costs, he added.

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Gene Linked to Kidney Failure

ScienceDaily (Oct. 16, 2012) A landmark paper identifying genetic signatures that predict which patients will respond to a life-saving drug for treating congestive heart failure has been published by a research team co-led by Stephen B. Liggett, MD, of the University of South Florida.

The study, drawing upon a randomized placebo-controlled trial for the beta blocker bucindolol, appears this month in the international online journal PLoS ONE. In addition to Dr. Liggett, whose laboratory discovered and characterized the two genetic variations, Christopher O'Connor, MD, of Duke University Medical Center, and Michael Bristow, MD, PhD, of ARCA biopharma and the University of Colorado Anschutz Medical Campus, were leading members of the research team.

Dr. Stephen Liggett, who joined USF just four months ago to lead the University's Center for Personalized Medicine and Genomics, was a senior author of the paper.

The analysis led to a "genetic scorecard" for patients with congestive heart failure, a serious condition in which the heart can't pump enough blood to meet the body's needs, said Dr. Liggett, the study's co-principal investigator and the new vice dean for research and vice dean for personalized medicine and genomics at the USF Morsani College of Medicine.

"We have been studying the molecular basis of heart failure in the laboratory with a goal of finding genetic variations in a patient's DNA that alter how drugs work," Dr. Liggett said. "We took this knowledge from the lab to patients and found that we can indeed, using a two-gene test, identify individuals with heart failure who will not respond to bucindolol and those who have an especially favorable treatment response. We also identified those who will have an intermediate level of response." The research has implications for clinical practice, because the genetic test could theoretically be used to target the beta blocker to patients the drug is likely to help. Equally important, its use could be avoided in patients with no likelihood of benefit, who could then be spared potential drug side effects. Prospective studies are needed to confirm that bucindolol would be a better treatment than other classes of beta blockers for a subset of patients with health failure.

Dr. Liggett collaborated with medical centers across the United States, including the NASDAq-listed biotech company ARCA biopharma, which he co-founded in Denver, CO. This genetic sub-study involved 1,040 patients who participated in the Beta-Blocker Evaluation of Survival Trial (BEST). The researchers analyzed mortality, hospital admissions for heart failure exacerbations and other clinical outcome indicators of drug performance.

"The results showed that the choice of the best drug for a given patient, made the first time without a trial-and-error period, can be accomplished using this two-gene test," Dr. Liggett said.

The genetic test discovered by the Liggett team requires less than 1/100th of a teaspoon of blood drawn from a patient, from which DNA is isolated. DNA is highly stable when frozen, so a single blood draw will suffice for many decades, Dr. Liggett said. And since a patient's DNA does not change over their lifetime, as new discoveries are made and other tests need to be run, it would not be necessary to give another blood sample, he added.

This is part of the strategy for the USF Center for Personalized Medicine and Genomics. The discovery of genetic variations in diseases can be targeted to predict three new types of information: who will get a disease, how the disease will progress, and the best drug to use for treatment.

"In the not too distant future, such tests will become routine, and patient outcomes, and the efficiency and cost of medical care will be impacted in positive ways. We also will move toward an era where we embrace the fact that one drug does not fit all," Dr. Liggett said. "If we can identify by straightforward tests which drug is best for which patient, drugs that work with certain smaller populations can be brought to the market, filling a somewhat empty pipeline of new drugs."

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Two-gene test predicts which patients with heart failure respond best to beta-blocker drug

Public release date: 16-Oct-2012 [ | E-mail | Share ]

Contact: Anne DeLotto Baier abaier@health.usf.edu 813-974-3303 University of South Florida (USF Health)

Tampa, FL (Oct. 16, 2012) -- A landmark paper identifying genetic signatures that predict which patients will respond to a life-saving drug for treating congestive heart failure has been published by a research team co-led by Stephen B. Liggett, MD, of the University of South Florida.

The study, drawing upon a randomized placebo-controlled trial for the beta blocker bucindolol, apprears this month in the online international journal PLoS ONE. In addition to Dr. Liggett, whose laboratory discovered and characterized the two genetic variations, Christopher O'Connor, MD, of Duke University Medical Center, and Michael Bristow, MD, PhD, of ARCA biopharma and the University of Colorado Anschutz Medical Campus, were leading members of the research team.

The analysis led to a "genetic scorecard" for patients with congestive heart failure, a serious condition in which the heart can't pump enough blood to meet the body's needs, said Dr. Liggett, the study's co-principal investigator and the new vice dean for research and vice dean for personalized medicine and genomics at the USF Morsani College of Medicine.

"We have been studying the molecular basis of heart failure in the laboratory with a goal of finding genetic variations in a patient's DNA that alter how drugs work," Dr. Liggett said. "We took this knowledge from the lab to patients and found that we can indeed, using a two-gene test, identify individuals with heart failure who will not respond to bucindolol and those who have an especially favorable treatment response. We also identified those who will have an intermediate level of response."

The research has implications for clinical practice, because the genetic test could theoretically be used to target the beta blocker to patients the drug is likely to help. Equally important, its use could be avoided in patients with no likelihood of benefit, who could then be spared potential drug side effects. Prospective studies are needed to confirm that bucindolol would be a better treatment than other classes of beta blockers for a subset of patients with health failure.

Dr. Liggett collaborated with medical centers across the United States, including the NASDAq-listed biotech company ARCA biopharma, which he co-founded in Denver, CO. This genetic sub-study involved 1,040 patients who participated in the Beta-Blocker Evaluation of Survival Trial (BEST). The researchers analyzed mortality, hospital admissions for heart failure exacerbations and other clinical outcome indicators of drug performance.

"The results showed that the choice of the best drug for a given patient, made the first time without a trial-and-error period, can be accomplished using this two-gene test," Dr. Liggett said.

The genetic test discovered by the Liggett team requires less than 1/100th of a teaspoon of blood drawn from a patient, from which DNA is isolated. DNA is highly stable when frozen, so a single blood draw will suffice for many decades, Dr. Liggett said. And since a patient's DNA does not change over their lifetime, as new discoveries are made and other tests need to be run, it would not be necessary to give another blood sample, he added.

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2-gene test predicts which patients with heart failure respond best to beta-blocker drug

Public release date: 15-Oct-2012 [ | E-mail | Share ]

Contact: Anita Srikameswaran 412-578-9193 University of Pittsburgh Schools of the Health Sciences

PITTSBURGH, Oct. 15, 2012 An increased risk of autism spectrum disorders (ASD) could result from an accumulation of many small, common genetic variations rather than large-effect, rare changes in the genetic code, according to a multicenter team led by researchers at the University of Pittsburgh School of Medicine. Their findings, published today in Molecular Autism, provide new insights into the genetic factors that underlie the neurodevelopmental condition.

Scientists have debated about the genetic contributions that lead to ASD in families where only one individual is affected, called simplex, versus those that have multiple affected family members, called multiplex, said senior author Bernie Devlin, Ph.D., associate professor, Department of Psychiatry, University of Pittsburgh School of Medicine.

"Our team compared simplex, multiplex and unaffected families using sophisticated quantitative genetic techniques," he said. "In families where only one child has an ASD, 40 percent of the risk is inherited while in families with more than one affected child, the risk rises to 60 percent."

For the project, the team examined thousands of DNA samples from families in the Simons Simplex Collection, in which one child but no parent or sibling had an ASD; the Autism Genome Project, in which more than one child had an ASD; and unaffected families enrolled in the HealthABC Program.

In addition to reviewing nearly 1 million gene variations, called single nucleotide polymorphisms (SNPs), to look for inheritance patterns associated with ASD, they also ran computer simulations to plot family trees using 1,000 SNPs that appear to impact the risk of ASD.

"These small gene changes can add up even though individually they do little harm," Dr. Devlin said. "This might explain why parents who do not have autism traits can have children who do."

Other research has shown that autism and related disorders also can arise from spontaneous variations in parental genes prior to conception as well as rare mutations of larger effect that are passed on, he noted. The multiple inheritance patterns could help explain the range of symptoms in the disorder.

The team included researchers from Yale University, the University of Michigan, University of California Los Angeles, Emory University, Harvard University and others. The effort was funded by grants from the Simons Foundation and National Institutes of Health grant MH057881.

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Additive effect of small gene variations can increase risk of autism spectrum disorders

Dundee University experts said P34 played a key role in causing the disease punctate PPK, which gives sufferers dots of hard, thickened skin which can cause pain and discomfort.

Irwin McLean, professor of human genetics in the Centre for Dermatology and Genetic Medicine at the university, said: "We have not only found this gene but we have been able to figure out how it works, which is very important.

"When the gene is disrupted or knocked out, the cells in the skin grow too fast and this results in these hard, thick, painful lesions which can be quite debilitating. When the gene is working properly then the skin forms normally.

"Knowing about this gene and what it does makes it easier for us to diagnose this form of skin disease and look towards developing new therapies.

"The pathway where this gene functions is a possible drug target although it will need more work to identify how we can take advantage of that."

Punctate PPK is one of a whole family of PPK skin diseases, each of which are relatively rare. It is estimated to affect around one in every 15,000 people in the UK.

The find was made possible by the use of next generation sequencing technology, which allows researchers to screen large amounts of genome data in a short space of time.

"This is a notable step forward in diagnosing skin diseases and the genetic causes behind them as this is research that we simply could not have done just a few years ago, We are now able to spot faulty genes and track their behaviour far more effectively," said Mr McLean.

The research is published in the journal Nature Genetics.

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Gene clues to help tackle skin disease

Fibulin-3 Represents a Sensitive and Specific Marker for the Diagnosis of Mesothelioma, Offering a Potential Tool for Early Diagnosis, Monitoring

Newswise NEW YORK, October 11, 2012 Researchers at NYU School of Medicine have discovered the protein product of a little-known gene may one day prove useful in identifying and monitoring the development of mesothelioma in early stages, when aggressive treatment can have an impact on the progression of disease and patient prognosis.

This gene produces a protein, fibulin-3, that is present in levels four to five times higher in the plasma of patients with mesothelioma compared to levels in asbestos-exposed patients or patients with several other conditions that cause tumors in the chest, said lead investigator Harvey I. Pass, MD, the Stephen E. Banner Professor of Thoracic Oncology, vice chair of research for the Department of Cardiothoracic Surgery and division chief of General Thoracic Surgery at NYU Langone Medical Center. We didnt know anything about this proteins role in mesothelioma before this study, but it may be an extremely useful tool for monitoring patients under treatment and possibly even diagnosing the development of mesothelioma at early stages. This marker is as exciting as any biomarker in mesothelioma today and warrants further research and validation by the scientific community.

The study appears in the October 11 issue of the New England Journal of Medicine.

Malignant mesothelioma is a rare but aggressive thoracic cancer that can develop several decades after exposure to asbestos. Diagnosis is often delayed until patients begin to show symptoms, including shortness of breath, cough, chest pain and, in advanced stages, weight loss and night sweats.

Often, patients with mesothelioma seek treatment when the shortness of breath becomes a noticeable problem. At that point, an x-ray typically reveals fluid in the chest, but many doctors fail to inquire about asbestos exposure upon receiving this report. Rather, doctors initially associate fluid in the chest with pneumonia or other inflammatory conditions, further delaying diagnosis, Dr. Pass explained.

Despite advances in chemotherapy, radiation therapy, and surgical management for malignant mesothelioma, the median survival for patients diagnosed with mesothelioma remains 12 months.

There is a great need for something some marker or test that will heighten the alarm that a patient presenting with new onset chest fluid could have mesothelioma, Dr. Pass said. Our findings indicate that a simple blood test may lead physicians to ask questions about asbestos exposure and consider whether the medical history and symptoms are compatible with mesothelioma.

Dr. Pass and his team are dedicated to finding diagnostic biomarkers genes, proteins or other molecules that are not only different in people with mesothelioma compared with cancerfree individuals who have been exposed to asbestos, but also different when compared to individuals with a variety of conditions that could cause fluid in the chest other than mesothelioma.

Fibulin-3 is a protein that floats around outside cells, coating the cells and free floating in blood plasma and extracellular fluid. For the current study, the research team compared levels of fibulin-3 in two separate cohorts of patients who were exposed to asbestos through their jobs: a group of iron workers and other asbestos-exposed individuals in Detroit, and a group of insulators in New York. Both cohorts included individuals who had been exposed to asbestos but did not develop mesothelioma, as well as individuals with a confirmed mesothelioma diagnosis. The researchers found that fibulin-3 expression was markedly elevated in the plasma of the patients with mesothelioma compared with the plasma of patients without mesothelioma. But the researchers wondered if maybe the elevated fibulin-3 levels were associated with other conditions, in addition to mesothelioma, that are associated with the development of chest tumors.

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High Levels of Blood-Based Protein Specific to Mesothelioma

(WASHINGTON) It sounds like a scene from a TV show: Someone sends a discarded coffee cup to a laboratory where the unwitting drinkers DNA is decoded, predicting what diseases lurk in his or her future.

A presidential commission found thats legally possible in about half the states and says new protections to ensure the privacy of peoples genetic information are critical if the nation is to realize the enormous medical potential of gene-mapping.

(MORE: Stem Cell Scientists Awarded Nobel Prize in Physiology and Medicine)

Such whole genome sequencing costs too much now for that extreme coffee-cup scenario to be likely. But the report being released Thursday says the price is dropping so rapidly that the technology could become common in doctors offices very soon and there are lots of ethical issues surrounding how, when and with whom the results may be shared.

Without public trust, people may not be as willing to allow scientists to study their genetic information, key to learning to better fight disease, the report warns.

If this issue is left unaddressed, we could all feel the effects, said Dr. Amy Gutmann, who chairs the Presidential Commission for the Study of Bioethical Issues.

Mapping entire genomes now is done primarily for research, as scientists piece together which genetic mutations play a role in various diseases. Its different than getting a lab test to see if you carry, say, a single gene known to cause breast cancer.

Gutmann said her commission investigated ahead of an anticipated boom in genome sequencing as the price drops from thousands today to about $1,000, cheaper than running a few individual gene tests.

The sheer amount of information in a whole genome increases the privacy concerns. For example, people may have their genomes sequenced to study one disease that runs in the family, only to learn theyre also at risk for something else with implications for relatives who may not have wanted to know.

Thursdays report shows a patchwork of protection. A 2008 federal law prohibits employers or health insurers from discriminating on the basis of genetic information, so that people dont put off a potentially important gene test for fear of losing their job or health coverage. But that law doesnt prevent denial of life insurance or long-term care insurance. Plus, theres little oversight of how securely genetic information is stored electronically, the report found.

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Bioethics Panel Urges More Gene Privacy Protection

Newswise Researchers from Mount Sinai School of Medicine have identified a six-gene signature that can be used in a test to predict survival in men with aggressive prostate cancer, according to new research published in the October issue of The Lancet Oncology. This is the first study to demonstrate how prognostic markers may be useful in a clinical setting.

Using blood from 202 men with treatment-resistant prostate cancer, researchers found six genes characteristic of treatment-resistant prostate cancer. Men with the six-gene signature were high-risk, with a survival time of 7.8 months, and men without it were low-risk, with a survival time of approximately 34.9 months. A replication study of 140 additional patients validated these findings. William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology of The Tisch Cancer Institute at The Mount Sinai Medical Center, led the research team.

"There is an urgent need for predictive models that help assess how aggressive the disease is in prostate cancer patients, as survival can vary greatly," said Dr. Oh. "Our six-gene model, delivered in a simple blood test, will allow clinicians to better determine the course of action for their patients, determine clinical trial eligibility, and lead to more targeted studies in late-stage disease."

Until now, disease prognosis in advanced prostate cancer could only be determined through clinical predictors or, occasionally, tumor biopsies with only moderately predictive results. This study shows the efficacy of the six-gene model blood test in determining length of survival.

The genes noted in the model suggest possible changes in the immune system related to late-stage disease that warrant further study as a target for immune-based therapies, said Dr. Oh.

Dr. Ohs team is conducting additional studies exploring the feasibility of the six-gene signature in other types of prostate cancer, the stability of the signature during the course of a patients illness, and the predictive ability of this signature in patients with prostate cancer treated with immune-based therapies.

This work was done in collaboration with colleagues at Dana-Farber Cancer Institute in Boston and Memorial Sloan-Kettering Cancer Center in New York City.

About The Mount Sinai Medical Center The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by US News and World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nations oldest, largest and most-respected voluntary hospitals. In 2011, US News and World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nations top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and US News and World Report and whose hospital is on the US News and World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place. For more information, visit http://www.mountsinai.org/.

Find Mount Sinai on: Facebook: http://www.facebook.com/mountsinainyc Twitter: @mountsinainyc YouTube: http://www.youtube.com/mountsinainy

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Researchers Discover Gene Signature that Predicts Prostate Cancer Survival