Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New hope for Gaucher patients

20.01.2014
What causes brain damage and inflammation in severe cases of Gaucher disease? Little is known about the events that lead to brain pathology in some forms of the disease, and there is currently no treatment available – a bleak outlook for sufferers and their families.

Now, scientists at the Weizmann Institute of Science have discovered a new cellular pathway implicated in Gaucher disease. Their findings, published today in Nature Medicine, may offer a new therapeutic target for the management of this disease, as well as other related disorders.


This shows the elevation of RIP3 in nuclei of neurons from neuronopathic Gaucher (red; arrows) disease mice.

Credit: Weizmann Institute of Science

Gaucher disease is a genetic disorder most prevalent among the Ashkenazi Jewish population. It is caused by a defect in a particular enzyme needed to break down a fatty substance, or lipid, called glucocerebroside. This results in the accumulation of glucocerebroside in various cells and organs, which prevents them from working properly. There are three subtypes of the disease: The most common form – Type 1 – is characterized by, among other symptoms, swelling and enlargement of the spleen and liver and disruption in the function of these organs, along with lung and bone problems. These symptoms can also affect individuals with Types 2 and 3 Gaucher disease, but what distinguishes them from Type 1 is the neurological involvement: Type 2 – the most severe form – causes extensive brain damage and death before two years of age, while Type 3 is a more progressive form of the disease that affects the brain, with patients often living into their early teens and adulthood.

But what exactly causes such a massive loss of nerve cells in Types 2 and 3 Gaucher disease? It has recently come to light that a certain biochemical pathway, of which a protein called RIP3 is a key player, is involved in triggering the cell death and inflammatory processes that can have severe consequences in a number of diseases. Dr. Einat Vitner and M.Sc. student Ran Salomon, in the lab of Prof. Tony Futerman of the Biological Chemistry Department, wondered whether this could also be one of the missing links in the understanding of the chain of molecular events leading to brain inflammation and nerve cell death in Gaucher disease. To find out, they induced Gaucher disease in mice possessing the RIP3 protein, as well as in mice lacking RIP3. In mice lacking the RIP3 protein, they demonstrated not only a significant improvement in motor coordination and brain pathology but also improved liver and spleen function. Their lifespan was also remarkably increased from approximately 35 days to more than 170 days.

Vitner: "These results are exciting, as they suggest a plausible new target for therapeutic intervention for all types of Gaucher disease; they have the potential, in the future, to greatly improve the patients' quality of life."

Indeed, although effective enzyme replacement therapy exists in which Gaucher patients are treated with injections of an intact version of the enzyme responsible for the normal breakdown of the lipid in healthy people, the cost of the lifelong treatment is approximately $200,000 per patient per year. Moreover, the enzyme is unable to get into the brain since it cannot cross the blood-brain barrier, rendering it ineffective in treating the neurological symptoms of Types 2 and 3 Gaucher disease. Hence, more affordable and alternative treatments are urgently needed.

"If successful, the new target could be used as either a complementary or alternative therapy for Gaucher disease, and with RIP3 proving to be a 'hot' cellular pathway in various pathologies, these results may also have implications in other neurodegenerative diseases, including related diseases such as Krabbe disease, and potentially other devastating brain diseases," says Futerman.

The Children's Gaucher Research Fund

Beginning with a memorial fund in honor of their son Gregory, who lost his life to Neuronopathic Gaucher (nGD) disease at the tender age of four, Greg and Deborah Macres have grown the Children's Gaucher Research Fund into a nonprofit charity that has raised over $2 million since its inception in 1999. In this grassroots organization in California, 100% of the donations go directly to research – the administrative costs are covered by the Macreses themselves, and it is supported by parents who have lost their children to nGD. It has been instrumental in enabling research aimed at finding a cure for Types 2 and 3 Gaucher Disease, such as that carried out in the lab of Prof. Tony Futerman at the Weizmann Institute, as well as providing support to families of children who battle this disease.

Greg: "We began funding Tony in 2001 and are truly grateful for his commitment to pursuing something that very few scientists have had an interest in. His new discovery, which has major implications not only for neuronopathic Gaucher Disease, but potentially and quite remarkably for Krabbe Disease, gives us encouragement. We hope to be able to continue this journey so that one day, our goal is reached in the form of words from a physician to the anxious parents of a sick child – 'Do not worry, we have a cure'."

Prof. Anthony H. Futerman's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases, which he heads; the M.D. Moross Institute for Cancer Research; and the Carolito Stiftung. Prof. Futerman is the incumbent of the Joseph Meyerhoff Professorial Chair of Biochemistry.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.

Weizmann Institute news releases are posted on the World Wide Web at http://wis-wander.weizmann.ac.il/, and are also available at http://www.eurekalert.org/

Yivsam Azgad | EurekAlert!
Further information:
http://www.weizmann.ac.il

More articles from Health and Medicine:

nachricht Using DNA origami to build nanodevices of the future
31.08.2015 | Institute for Integrated Cell-Material Sciences at Kyoto University

nachricht An ounce of prevention: Research advances on 'scourge' of transplant wards
28.08.2015 | University of Wisconsin-Madison

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: How wind sculpted Earth's largest dust deposit

China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from University of Arizona geoscientists. The study is the first to explain how the steep-fronted plateau formed.

China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from...

Im Focus: An engineered surface unsticks sticky water droplets

The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.

Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...

Im Focus: Increasingly severe disturbances weaken world's temperate forests

Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.

"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...

Im Focus: OU astrophysicist and collaborators find supermassive black holes in quasar nearest Earth

A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.

The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...

Im Focus: What would a tsunami in the Mediterranean look like?

A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).

Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking conference in Heidelberg for outstanding mathematicians and computer scientists

20.08.2015 | Event News

Scientists meet in Münster for the world’s largest Chitin und Chitosan Conference

20.08.2015 | Event News

Large agribusiness management strategies

19.08.2015 | Event News

 
Latest News

How wind sculpted Earth's largest dust deposit

02.09.2015 | Earth Sciences

Risk of financial crisis higher than previously estimated

02.09.2015 | Studies and Analyses

Siemens sells 18 industrial gas turbines to Thailand

01.09.2015 | Press release

VideoLinks
B2B-VideoLinks
More VideoLinks >>>