Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Recreating ’Flowers for Algernon’ with a happy ending

08.11.2005


UCLA scientists use statins to overcome learning disabilities in mice



In a surprise twist that recalls the film classic "Flowers for Algernon," but adds a happy ending, UCLA scientists used statins, a popular class of cholesterol drugs, to reverse the attention deficits linked to the leading genetic cause of learning disabilities. The Nov. 8 issue of Current Biology reports the findings, which were studied in mice bred to develop the disease, called neurofibromatosis 1 (NF1).
The results proved so hopeful, that the Food and Drug Administration approved the use of the drugs in three clinical trials currently under review to test the effect of statins in children and adults born with NF1. The findings could help the estimated 35 million Americans who struggle with learning disabilities.

"Learning disabilities and mental retardation each affect five percent of the world population," said Dr. Alcino Silva, professor of neurobiology, psychiatry and psychology at the David Geffen School of Medicine at UCLA. "Currently, there are no treatment options for these people. That’s why our findings are so exciting from a clinical perspective."



In an earlier study, Silva and his colleagues linked NF1’s learning problems to a protein called Ras, a protein that regulates how brain cells talk to each other. This communication is what enables learning to take place. The NF1 mutation creates hyperactive Ras, which disrupts cellular conversation and undermines the learning process.

"The act of learning creates physical changes in the brain, like grooves on a record," said Silva. "But surplus Ras tips the balance between switching signals on and off in the brain. This interrupts the delicate cell communication needed by the brain to record learned information."

The UCLA team began searching for a safe drug that would zero in on Ras and overcome its hyperactivity without causing harmful side effects over long-term use.

"It became something of a Quixotic quest -- an impossible dream," Silva admitted. "We thought, ’Wouldn’t it be nice to find a drug that is already FDA-approved, safe for lifetime use and could be tested in mice and humans with NF1?’ Fortunately, our optimism was rewarded."

It took a medical student in Silva’s lab to identify the drug and connect it with NF1. Steve Kushner, a scholar in UCLA’s MD/PhD program, learned in a clinical rotation about statins, the drugs already prescribed to millions of people worldwide to lower cholesterol.

"Steve raced into my lab and shared what he’d learned: statins work on the Ras protein that is altered by NF1 and play a key role in learning and memory," recalled Silva. "It was the researcher’s equivalent of finding a suitcase stuffed with a million dollars."

Statin drugs lower cholesterol by blocking the effects of certain fats. Because Ras requires fat to function, less fat results in less Ras. With reduced Ras activity, the brain cells are able to communicate properly in mice with NF1, allowing normal learning to take place.

"NF1 interrupts how cells talk to each other, which results in learning deficits," said Silva. "Statins act on the root of the problem and reverse these deficits. This enables the process of learning to physically change the brain and create memory."

Silva’s lab tested the effects of statins on mice that were bred with the NF1 mutation. The animals displayed the same symptoms as people with NF1: attention deficits, learning problems and poor physical coordination.

First author Weidong Lee, a UCLA postdoctoral fellow, ran three tests to compare the behavior of NF1 mice treated with statins to NF1 mice who received a placebo. Then he compared both groups to normal mice.

First, he trained the mice to follow a blinking light in order to find a food reward. The NF1 mice on statins showed a 30 percent improvement in their ability to pay attention, outperforming the normal mice.

Second, he trained the mice to memorize spatial clues in order to navigate a water maze and swim to a platform. The normal animals learned to find the platform in seven days; the NF1 mice took 10. After receiving statins, the NF1 mice outraced the normal mice.

Third, Lee tested coordination by training the mice to balance while running on a rotating log, which gradually increased in speed. At first, the NF1 mice would jump off as the log spun faster. But statin therapy enabled the NF1 mice to perform as well as their normal counterparts.

"This is mind-blowing – we think we have a real fundamental reason to be optimistic," explained Silva. "Here is a drug that affects a key learning and memory pathway, and completely rescues the most common genetic cause for learning disabilities. We don’t have to do extensive clinical trials for toxicity or safety – these were already completed for other uses."

Elaine Schmidt | EurekAlert!
Further information:
http://www.mednet.ucla.edu

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>