Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers find potential treatment for Huntington's disease

Better understanding of synaptic activity may support 'use it or lose it' hypothesis

Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease.

In contrast, excessive extrasynaptic activity (aberrant electrical activity in the brain, usually not associated with communication between nerve cells) enhances the misfolded proteins' deadly effects. Researchers also found that the drug Memantine, which is approved to treat Alzheimer's disease, successfully treated Huntington's disease in a mouse model by preserving normal synaptic electrical activity and suppressing excessive extrasynaptic electrical activity. The research was published in the journal Nature Medicine on November 15.

Huntington's disease is a hereditary condition caused by a mutated huntingtin gene that creates a misfolded, and therefore dysfunctional, protein. The new research shows that normal synaptic receptor activity makes nerve cells more resistant to the mutant proteins. However, excessive extrasynaptic activity contributed to increased nerve cell death. The research team found that low doses of Memantine reduce extrasynaptic activity without impairing protective synaptic activity. The work was led by Stuart A. Lipton, M.D., Ph.D., director of the Del E. Webb Center for Neuroscience, Aging and Stem Cell Research at Burnham and professor in the department of Neurosciences and attending neurologist at the University of California, San Diego and Michael R. Hayden, M.D., Ph.D., University Killam professor in the department of Medical Genetics at UBC and director of the Centre for Molecular Medicine and Therapeutics at the Child & Family Research Institute.

"Chronic neurodegenerative diseases like Huntington's, Alzheimer's and Parkinson's are all related to protein misfolding," said Dr. Lipton. "We show here, for the first time, that electrical activity controls protein folding, and if you have a drug that can adjust the electrical activity to the correct levels, you can protect against misfolding. Also, this verifies that appropriate electrical activity is protective, supporting the 'use it or lose it theory' of brain activity at the molecular level. For example, this finding may explain why epidemiologists have found that 'using' your brain by performing crossword puzzles and other games can stave off cognitive decline in diseases like Alzheimer's."

In the new study, researchers initially tested nerve cell cultures transfected with mutant Huntingtin protein and found that reducing excessive NMDA-type glutamate receptor activity with Memantine and other antagonists protected the nerve cells (glutamate receptors are the main trigger of excitatory electrical activity in the brain but in excess can cause nerve cell death, a process called excitotoxicity). They also found that normal synaptic activity was protective. Subsequently, they treated Huntington's disease model mice with both high and low doses of Memantine and found that the low doses were protective by blocking pathological extrasynaptic activity, while high-dose Memantine encouraged disease progression because it also blocked the protective synaptic NMDA receptor activity.

"For a long time it's been known that excitotoxicity is an early marker of Huntington's disease," said Dr. Hayden. "However, now we have dissected the mechanism by which this happens, particularly focusing on NMDA receptors outside the synapse. This creates novel therapeutic opportunities to modulate these receptors with potential protective effects on nerve cells."

A small human clinical trial of Memantine for Huntington's disease has also recently shown positive effects. Larger, international clinical trials are now being planned.

Dr. Lipton is the named inventor on worldwide patents for the use of Memantine (marketed in the USA under the name Namenda®) in neurodegenerative disorders, including Alzheimer's and Huntington's disease. He is credited with the groundbreaking discovery more than ten years ago of how Memantine works in the brain and for spearheading early human clinical trials with the drug.

About Burnham Institute for Medical Research

Burnham Institute for Medical Research is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The institute ranks among the top four institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. For the past decade (1999-2009), Burnham ranked first worldwide in the fields of biology and biochemistry for the impact of its research publications (defined by citations per publication), according to the Institute for Scientific Information.

Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Burnham is a nonprofit public benefit corporation. For more information, please visit

About the Centre for Molecular Medicine and Therapeutics

CMMT is a premier genetics science research centre in Canada and the world, dedicated to unraveling and solving the many genetic questions surrounding human illness and well being. It is a unique collaboration of committed scientists and researchers, who participate in multidisciplinary teams with the optimal combination of expertise, to find new approaches to treatment and prevention that can overcome the causes of illness. Affiliated with the University of British Columbia and the Child & Family Research Institute, CMMT conducts discovery research and translates that research into novel and effective clinical and therapeutic strategies to promote health. For more information, visit

About the Child & Family Research Institute

CFRI conducts discovery, clinical and applied research to benefit the health of children and families. It is the largest institute of its kind in Western Canada. CFRI works in close partnership with UBC, BC Children's and Sunny Hill Health Centre for Children, BC Women's, PHSA, and BC Children's Hospital Foundation. CFRI has additional important relationships with BC's five regional health authorities and with BC academic institutions Simon Fraser University, the University of Victoria, the University of Northern British Columbia, and the British Columbia Institute of Technology. For more information, visit

About the University of British Columbia

UBC is one of Canada's largest and most prestigious public research and teaching institutions and consistently ranks among the top 40 universities in the world. It offers a range of innovative undergraduate, graduate and professional programs in the arts, sciences, medicine, law, commerce and other faculties. UBC has particular strengths in biotechnology, ranks in the top 10 universities in North America and number one in Canada for commercializing research and for its patent activity in the life sciences. For more information, visit

Josh Baxt | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Inflammation Triggers Unsustainable Immune Response to Chronic Viral Infection
24.10.2016 | Universität Basel

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

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: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>