Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bone marrow transplant arrests symptoms in model of Rett syndrome

19.03.2012
Results emphasize immune component of autism spectrum disorder

A paper published online today in Nature describes the results of using bone marrow transplant (BMT) to replace faulty immune system cells in models of Rett Syndrome. The procedure arrested many severe symptoms of the childhood disorder, including abnormal breathing and movement, and significantly extended the lifespan of Rett mouse models.

Exploring the function of microglia deficient in methyl-CpG binding protein 2 (Mecp2), the protein encoded by the "Rett gene," principal investigator Jonathan Kipnis, Ph.D. and his team at the University of Virginia School of Medicine uncovered a completely novel approach to this devastating neurological syndrome. The work was funded by the Rett Syndrome Research Trust and the Rett Syndrome Research Trust UK.

Rett Syndrome, the most physically disabling of the autism spectrum disorders, is caused by random mutations in the gene MECP2. Predominantly affecting girls, symptoms usually manifest between 6 and 18 months of age, when a frightening regression begins. Children lose acquired language skills and functional hand use; movement deteriorates as other Rett symptoms appear. These may include disordered breathing, Parkinsonian tremors, severe anxiety, seizures, digestive and circulatory problems and a range of autonomic nervous system and orthopedic abnormalities Although most children survive to adulthood, many are wheelchair-bound, rely on feeding tubes, are unable to communicate and require total, lifelong care.

Kipnis was drawn to Rett Syndrome from his perspective as a neuroimmunologist. "What began as intellectual curiosity," he explains, "has become an intense personal commitment to studying the correlation between neurological function and the immune system in Rett Syndrome. The impact of BMT on so many different symptoms has triggered a flood of experiments we are now pursuing at full speed."

The brain is largely comprised of several types of glial cells, which have diverse and complex functions that include sustaining a healthy environment for neuronal growth and maintenance. Microglia are small glial cells that participate in the brain's immune response. One of their roles is to clean up normal cellular debris in the brain through the process of phagocytosis. Kipnis and his team discovered that when microglia lack properly functioning Mecp2, they are unable to perform this crucial duty efficiently. Because microglia are derived from immune progenitor cells, it is possible to replace them via a bone marrow transplant.

First author Noël Derecki and his colleagues began their work with male Rett mouse models, which lack any Mecp2. These Mecp2-null mice mimic the human disorder, with neurological symptoms beginning to appear at about 4 weeks of age and an approximate life expectancy of only 8 weeks. Radiation treatment was administered at 4 weeks, followed by a bone marrow transplant from normal (wild-type) mice. As engraftment - the migration and repopulation of new microglia - took place, the Rett mice began to grow instead of fail. Body and brain sizes approached those of wild-type mice, gait improved and mobility increased significantly. There were no signs of the severe tremors seen in untreated mice. Apneas and other breathing irregularities were markedly diminished. The oldest of these mice is now almost a year. Work with female Rett mouse models at more advanced stages of disease is currently underway.

Gail Mandel, Ph.D., whose Rett research focuses on astrocytes, another type of glial cell impaired by mutations in MECP2, comments, "A fascinating aspect of these findings is the data suggesting that deficits in the engulfing properties of microglia are a crucial aspect of Rett neuropathology. It will now be necessary to develop cellular assays to determine all the ways these immune cells are bolstering neuronal functions and whether they can be therapeutically harnessed." Dr. Mandel is a Senior Scientist at the Vollum Institute and a Professor in the Department of Biochemistry and Molecular Biology in the School of Medicine at Oregon Health & Science University and an Investigator of the Howard Hughes Medical Institute.

Monica Coenraads, Executive Director of the Rett Syndrome Research Trust added, "I've been in almost daily contact with Dr. Kipnis since he brought his very original proposal to RSRT, and have been amazed to see the development of this brutal disease stopped in its tracks. A question that arises, of course, is whether replacing faulty immune cells with healthy microglia through bone marrow transplant would arrest or ameliorate already existing symptoms in humans. We do know of a case in which a girl with Rett Syndrome who was treated for leukemia gained considerable communication skills after a bone marrow transplant, and was able to converse with her mother for the first time in their lives. RSRT is in the process of exploring bone marrow transplant as a treatment modality, with full awareness of the serious nature of such a trial. In research, we are risk-takers. In clinical application, we are conservative and will be examining this carefully as more information emerges."

Adds Noël Derecki, "Our encouraging results point to how surprisingly tractable this severe disorder proves to be, at least in the lab. We are currently exploring how bone marrow transplantation might affect Rett symptoms once they have become more advanced, and whether there are other effective ways of modulating immune responses and subsequent effects in the central nervous system."

The paper, authored by Noël C. Derecki, James C. Cronk, Zhenjie Lu, Eric Xu, Stephen B.G. Abbott, Patrice G. Guyenet and Jonathan Kipnis, is entitled Wild type microglia arrest pathology in a mouse model of Rett Syndrome. doi:10.1038/nature10907

About the Rett Syndrome Research Trust

The Rett Syndrome Research Trust is the premier organization exclusively devoted to global research on Rett Syndrome and related MECP2 disorders. Our goal is to heal children and adults who will otherwise suffer the effects of these disorders for the rest of their lives. To learn more about the Trust, please visit www.ReverseRett.org

Our partners in supporting this work are parents' organizations worldwide including the Rett Syndrome Research & Treatment Foundation (Israel), Stichting Rett Syndrome (Holland), Rett Syndrom Deutschland e.V., Skye Wellesley Foundation (UK) and American organizations, The Kate Foundation for Rett Syndrome Research, Girl Power 2 Cure and Rocky Mountain Rett Association.

Monica Coenraads | EurekAlert!
Further information:
http://www.rsrt.org

More articles from Health and Medicine:

nachricht Chronic stress induces fatal organ dysfunctions via a new neural circuit
21.08.2017 | Hokkaido University

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>