Buck scientists correct Huntington's disease mutation in induced pluripotent stem cells

Corrected cells are generating normal neurons in mouse model of the disease

2012-06-29

(Press-News.org) Researchers at the Buck Institute for Research on Aging have corrected the genetic mutation responsible for Huntington's Disease (HD) using a human induced pluripotent stem cell (iPSC) that came from a patient suffering from the incurable, inherited neurodegenerative disorder. Scientists took the diseased iPSCs, made the genetic correction, generated neural stem cells and then transplanted the mutation-free cells into a mouse model of HD where they are generating normal neurons in the area of the brain affected by HD. Results of the research are published in the June 28, 2012 online edition of the journal Cell Stem Cell.

iPSCs are reverse-engineered from human cells such as skin, back to a state where they can be coaxed into becoming any type of cell. They can be used to model numerous human diseases and may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory. "We believe the ability to make patient-specific, genetically corrected iPSCs from HD patients is a critical step for the eventual use of these cells in cell replacement therapy," said Buck faculty Lisa Ellerby, PhD, lead author of the study. "The genetic correction reversed the signs of disease in these cells – the neural stem cells were no longer susceptible to cell death and the function of their mitochondria was normal." Ellerby said the corrected cells could populate the area of the mouse brain affected in HD, therefore, the next stage of research involves transplantation of corrected cells to see if the HD-afflicted mice show improved function. Ellerby said these studies are important as now we can deliver patient-specific cells for cell therapy, that no longer have the disease causing mutation.

Huntington's disease (HD) is a devastating, neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems. It typically becomes noticeable in mid-adult life, with symptoms beginning between 35 and 44 years of age. Life expectancy following onset of visual symptoms is about 20 years. The worldwide prevalence of HD is 5-10 cases per 100,000 persons. More than a quarter of a million Americans have HD or are "at risk" of inheriting the disease from an affected parent. Key to the disease process is the formation of specific protein aggregates (essentially abnormal clumps) inside some neurons.

All humans have two copies of the Huntingtin gene (HTT), which codes for the protein Huntingtin (Htt). Part of this gene is a repeated section called a trinucleotide repeat, which varies in length between individuals and may change between generations. When the length of this repeated section reaches a certain threshold, it produces an altered form of the protein, called mutant Huntingtin protein (mHtt). Scientists in the Ellerby lab corrected the mutation by replacing the expanded trinucleotide repeat with a normal repeat using homologous recombination. Homologous recombination is a type of genetic recombination where two molecules of DNA are exchanged. In this case the diseased DNA sequence is exchanged for the normal DNA sequence.

INFORMATION:

Contributors to the work:

Mahru An and Ningzhe Zhang are shared first authors of this study. Other Buck Institute researchers involved in the study include Gary Scott, Daniel Montoro, Tobias Wittkop, and faculty members Sean Mooney and Simon Melov. The work was funded by the Buck Institute and the National Institutes of Health.

About the Buck Institute for Research on Aging

The Buck Institute is the U.S.'s first and foremost independent research organization devoted to Geroscience – focused on the connection between normal aging and chronic disease. Based in Novato, CA, The Buck is dedicated to extending "Healthspan", the healthy years of human life and does so utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and those focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer's and Parkinson's, cancer, cardiovascular disease, macular degeneration, diabetes and stroke. In their collaborative research, they are supported by the most recent developments in genomics, proteomics and bioinformatics. For more information: www.thebuck.org.

ELSE PRESS RELEASES FROM THIS DATE:

Lymph node roundabout

2012-06-29

This press release is available in German. An organism's ability to make new antibodies and use them to optimize its own immune defenses is of central importance in the fight against pathogens. In the case of severe infections, the overall relative speed with which an immune response proceeds could mean the difference between life and death. An international team of scientists, among them systems immunologist Prof. Michael Meyer-Hermann of the Helmholtz Centre for Infection Research (HZI) of Braunschweig, Germany, has now found that asymmetric division of antibody-producing ...

With mind-reading speller, free-for-all conversations that are silent and still

2012-06-29

Researchers have come up with a device that may enable people who are completely unable to speak or move at all to nevertheless manage unscripted back-and-forth conversation. The key to such silent and still communication is the first real-time, brain-scanning speller, according to the report published online on June 28 in Current Biology, a Cell Press publication. The new technology builds on groundbreaking earlier uses of fMRI brain scans to assess consciousness in people described as being in an unconscious, vegetative state and to enable them to answer yes and no ...

Study on fungi helps explain coal formation and may advance future biofuels production

2012-06-29

A new study--which includes the first large-scale comparison of fungi that cause rot decay--suggests that the evolution of a type of fungi known as white rot may have brought an end to a 60-million-year-long period of coal deposition known as the Carboniferous period. Coal deposits that accumulated during the Carboniferous, which ended about 300 million years ago, have historically fueled about 50 percent of U.S. electric power generation. In addition, the study provides insights about diverse fungal enzymes that might be used in the future to help generate biofuels, ...

How an ancestral fungus may have influenced coal formation

2012-06-29

For want of a nail, the nursery rhyme goes, a kingdom was lost. A similar, seemingly innocuous change—the evolution of a lineage of mushrooms—may have had a massive impact on the carbon cycle, bringing an end to the 60-million year period during which coal deposits were formed. Coal generated nearly half of the roughly four trillion kilowatt-hours of electricity consumed in the United States in 2010, according to the U.S. Energy Information Administration. This fuel is actually the fossilized remains of plants that lived from around 360 to 300 million years ago. An international ...

U Alberta resets date of earliest animal life by 30 million years

2012-06-29

University of Alberta researchers have uncovered physical proof that animals existed 585 million years ago, 30 million years earlier than all previous established records show. The discovery was made U of A geologists Ernesto Pecoits and Natalie Aubet in Uruguay. They found fossilized tracks of a centimetre long, slug-like animal left behind 585 million years ago in a silty sediment. Along with other U of A researchers, the team determined that the tracks were made by a primitive animal called a bilaterian, which is distinguished from other non-animal, simple life ...

Both innate and adaptive immune responses are critical to the control of influenza

2012-06-29

Both innate and adaptive immune responses play an important role in controlling influenza virus infection, according to a study, published in the Open Access journal PLoS Computational Biology, by researchers from Oakland University, Michigan, and Los Alamos National Laboratory, New Mexico, USA. Influenza, as a contagious respiratory illness remains a major public health problem worldwide. Seasonal and pandemic influenza results in approximately 3 to 569 million cases of severe illness and approximately 250,000 to 500,000 deaths worldwide. Although most infected subjects ...

A group of fungi marked the end of the coal age 300 million years ago

2012-06-29

300 million years ago, the Earth suddenly interrupted massive production of coal. This fact determined the end of the Carboniferous, a period of the Paleozoic Era that had started 60 million years before, characterized by the successive formation of large carbon beds arising from accumulation and burial of ancient trees growing up in vast marshy forests. An international scientific team with participation of the Spanish National Research Council (CSIC) has found out that the end of this coal age coincided with the origin of a group of highly specialized fungi. The results, ...

CSIC recovers part of the genome of 2 hunter-gatherer individuals from 7,000 years ago

2012-06-29

A team of scientists, led by researcher Carles Lalueza-Fox from CSIC (Spanish National Research Council), has recovered - for the first time in history - part of the genome of two individuals living in the Mesolithic Period, 7000 years ago. Remains have been found at La Braña-Arintero site, located at Valdelugueros (León), Spain. The study results, published in the Current Biology magazine, indicate that current Iberian populations don't come from these groups genetically. The Mesolithic Period, framed between the Paleolithic and Neolithic Periods, is characterized by ...

Dramatic change spotted on a faraway planet

2012-06-29

Astronomer Alain Lecavelier des Etangs (CNRS-UPMC, France) and his team used Hubble to observe the atmosphere of exoplanet HD 189733b [1] during two periods in early 2010 and late 2011, as it was silhouetted against its parent star [2]. While backlit in this way, the planet's atmosphere imprints its chemical signature on the starlight, allowing astronomers to decode what is happening on scales that are too tiny to image directly. The observations were carried out in order to confirm what the team had previously seen once before in a different planetary system: the evaporation ...

Rice researchers develop paintable battery

2012-06-29

HOUSTON – (June 28, 2012) – Researchers at Rice University have developed a lithium-ion battery that can be painted on virtually any surface. The rechargeable battery created in the lab of Rice materials scientist Pulickel Ajayan consists of spray-painted layers, each representing the components in a traditional battery. The research appears today in Nature's online, open-access journal Scientific Reports. "This means traditional packaging for batteries has given way to a much more flexible approach that allows all kinds of new design and integration possibilities ...

Buck scientists correct Huntington's disease mutation in induced pluripotent stem cells

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: