Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Interferon-beta aids balance and movement in mice with spinocerebellar ataxia 7

10.06.2013
First in vivo study of the treatment for this condition shows significant physical improvement

Paris, France: The group of genetic conditions known as spinocerebellar ataxias currently have no treatment or cure and are always fatal, in the case of affected children at an early age. Symptoms include a progressive lack of co-ordination of gait, and poor co-ordination of hands, speech and eye movements, due to a failure of co-ordination of muscle movements.

Now researchers from France and the US have found a new way of controlling the symptoms and significantly improving the physical condition of animal models of the disease, the annual conference of the European Society of Human Genetics will hear today (Monday June 10).

Dr. Annie Sittler, from the Centre National de la Recherche Scientifique (CNRS), working in the team of Professor Alexis Brice at the research centre Brain and Spinal Cord Institute (CR-ICM), Paris, France described the team's work in the field of polyglutamine disease, a group of neurodegenerative conditions involving abnormal protein conformation. "Accumulation of a polyglutamine-containing protein known as mutant ataxin -7 is responsible for neurotoxicity, neuronal dysfunction, and eventually neuronal death", she explains. "We had previously shown in cells that mutant ataxin-7 was degraded in nuclear bodies, structures found in the nucleus of cells, by a protein known as promyeloctyic leukaemia protein or PML, and that interferon-beta could help with this process and protect against disease."

The researchers used a mouse model of a particular form of spinocerebellar ataxia known as SCA7. The genetically-modified 'knock-in' mice develop the severe type of the disease, similar to the infantile human version, and have a very short lifespan of around 14 weeks. They were injected with mouse interferon-beta three times a week, starting at five weeks of age, just before their first symptoms of disease were due to appear. Investigation of their brains post-mortem showed that the mice who had received the interferon-beta, as opposed to those in the control group, had a reduced load of mutant ataxin-7.

On the physical level, substantial improvements in the interferon-beta treated mice were noticed. "At twelve weeks of age the physical performance of the mice that received the active substance was significantly improved compared to the control group. We gave them a locotronic test, where they have to cross a kind of ladder. This test is used to check motor co-ordination when walking. We also put them through a beam-walking test, which enables us to measure their balance and limb co-ordination. The treated mice did much better in both of these tests", Dr. Sittler will say.

Further proof of the positive effects of interferon-beta came from analysis of the PML nuclear bodies, involved in many cellular processes such as transcriptional regulation and apoptosis. A subset of these nuclear bodies is responsible for regulating the degradation of accumulated misfolded proteins in the cell nucleus. The treated mice had more, and very much larger, PML bodies, and they were present in the Purkinje cells, responsible for motor co-ordination emanating from the cerebellum The researchers further found that these PML bodies were clastosomes, the specialised nuclear bodies involved in the degradation of mutant ataxin-7 and other polyglutamine-containing proteins. "This, together with the physical improvements we saw in the interferon-beta treated mice, was the proof we needed that our findings in the cell could be successfully transferred to living animals", says Dr. Sittler.

"Now that we have found that interferon-beta can slow progression of disease in SCA7 mice, we believe that, after confirmation in another mouse model, it would be merited to test its effects on humans in a clinical trial,", she will say. "Such trials are difficult in rare diseases, since a special design is needed to test a hypothesis on a small number of patients. However, there are a number of other polyglutamine diseases, for example Huntington's, where patient numbers are larger, and the effects of the condition just as devastating. We hope that our results will encourage others to collaborate with us in order that we may be able to pursue our research to the benefit of all those afflicted with spinocerebellar disorders."

Mary Rice | EurekAlert!
Further information:
http://www.eshg.org

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>