Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Could a Cancer Drug Prevent Learning Disabilities in Some Kids?

30.08.2012
U-M scientists stop abnormal brain cell growth in mice with neurofibromatosis using experimental tumor drug, make new discoveries in neural stem cells

A drug originally developed to stop cancerous tumors may hold the potential to prevent abnormal brain cell growth and learning disabilities in some children, if they can be diagnosed early enough, a new animal study suggests.

The surprising finding sets the stage for more research on how anti-tumor medication might be used to protect the developing brains of young children with the genetic disease neurofibromatosis 1 -- and other diseases affecting the same cellular signaling pathway.

The findings, made in mice, are reported in the journal Cell by scientists at the University of Michigan Medical School and their colleagues. The results are also important to understanding the stem cells that become different brain cells.

Neurofibromatosis 1, or NF1, affects one in every 3,000 children, and causes benign tumors to grow throughout the body, large head size and other issues. Many children with NF1 also struggle with learning to read, write, do math and behave well.

This impact on brain function is considered the most common serious issue caused by NF1, and often appears before other symptoms, except for brown patches on the skin that are often mistaken for birthmarks. But while the tumors that erupt mostly later in life have been well-studied, NF1’s effect on brain function isn’t understood.

In the new paper, the team studied neural stem cells – a kind of master cell that can become any type of neural tissue. In newborn mice with two copies of the genetic mutation that causes NF1, neural stem cells in a key area of the brain were far more likely to produce a kind of “helper” nerve cell called glia. They produced far fewer cells called neurons, which send and receive crucial signals in the brain and body.

The scientists then took aim at this abnormal cell growth by giving the mice an experimental drug that has already been used in clinical trials for advanced cancer. Called PD0325901, the drug blocks a specific action within cells called the MEK/ERK pathway. It’s one of a class of drugs known as MEK inhibitors.

Mice with the NF1 mutation that got the drug from birth developed normally – in stark contrast to mice with the same genetic mutations that didn’t receive the drug. The untreated mice appeared normal at birth, but within a few days had become hunched and scruffy, with abnormal growth of their bodies and brain cells.

The new paper’s senior author, Yuan Zhu, Ph.D., cautions that the particular drug in the trial may not be appropriate to give to children who have been diagnosed with NF1. But other MEK inhibitors are being developed against cancer.

“The important thing is that we have shown that by treating during this brief window of time early in life, when neural stem cells in a developing brain still have time to ‘decide’ what kind of cell to become, we can cause a lasting effect on neural development,” he says. Zhu is an associate professor of internal medicine, in the Division of Molecular Medicine and Genetics, and in the Department of Cell & Developmental Biology, at the Medical School.

The scientists didn’t study the drug’s effect on the behavior or learning ability of the mice, nor their tendency to develop benign brain tumors that can occur in NF1. In order for any such drug-based intervention to work most effectively, he notes, it would have to be given soon after developmental delays or benign tumors are noted in an infant or toddler, and after a NF1 diagnosis is made.

About half of all people with NF1 inherited the mutated gene from a parent, while about half developed it spontaneously in the womb. The disease affects individual patients very differently -- one child born to a parent with mild NF1 can have a severe form of the disease, while their siblings can have mild or moderate symptoms.

Some people with NF1 have a “double hit” form of the disease, where both copies of the gene are mutated in certain body cells. The second mutation, the scientists say, likely occurs in a neural stem cell that goes on to produce unusual neural cells. These patients often have severe learning disabilities, and an enlarged corpus callosum -- a structure that connects the two halves of the brain and contains a large concentration of glia, the same cells that the mice in the new study had larger numbers of.

In addition to NF1, the researchers predict that their findings may have importance for patients with other genetic conditions that affect the same general cell-signaling pathway called RAS. Collectively called neuro-cardio-facial-cutaneous (NCFC) syndromes or ‘‘RASopathies”, they include Leopard syndrome, Noonan syndrome, Costello syndrome and Leguis syndrome – all of which, like NF1, affect the brains, circulation system and the face or head.

The new research is based on several other discoveries made by current or former U-M faculty. The gene for NF1 was discovered in the late 1980s by Francis Collins, M.D., Ph.D. when he was a faculty member at the U-M Medical School, together with colleagues from other institutions. Collins is now director of the National Institutes of Health. That discovery paved the way for a genetic test that can now help definitively diagnose children with NF1, and guide their treatment.

Judith Sebolt Leopold, Ph.D., a research associate professor of radiology at the U-M Medical School, was a key member of the research team that developed PD0325901 while she worked at the Pfizer Research Laboratory formerly located in Ann Arbor.

The drug was first used in a cancer clinical trial in 2005, which was stopped when side effects on the retinas of some participants’ eyes were noted. A new trial, using the drug in combination with another one, and comparing that combination with another drug combination, is now under way. Other MEK inhibitors, or MEKi drugs, are also in testing around the world, as scientists zero in on the RAS pathway as an important player in all kinds of cancer including melanoma.

In addition to Zhu, the research team includes U-M postdoctoral research fellow and former Zhu graduate student Yuan Wang, Ph.D.; Edward Kim, B.S.; former postdoctoral research fellow Xiaojing Wang, Ph.D.; and colleagues from other institutions Bennett G. Novitch, Kazuaki Yoshikawa and Long-Sheng Chang.

Reference: Cell, Volume 150, Issue 4, 816-830, 17 August 2012

Funding: NIH (1R01 NINDS NS053900) and DOD (W81XWH-11-1-0251)

Neurofibromatosis testing is available from the Pediatrics Genetics clinic at the U-M C.S. Mott Children’s Hospital. Visit mottchildren.org/medical-services/ped-genetics or call 734-764-0579.

Kara Gavin | Newswise Science News
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht Oestrogen regulates pathological changes of bones via bone lining cells
28.07.2017 | Veterinärmedizinische Universität Wien

nachricht Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

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

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

Programming cells with computer-like logic

27.07.2017 | Life Sciences

Identified the component that allows a lethal bacteria to spread resistance to antibiotics

27.07.2017 | Life Sciences

Malaria Already Endemic in the Mediterranean by the Roman Period

27.07.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>