ALSA Monthly Journal News for November 2005

Posted 12-04-05

Roberta Friedman, Ph.D., ALSA Research Department Information Coordinator

While this summary is not exhaustive, it does include some of the most recent advances. If you would like certain news items featured, please contact the Research Department at researchgrants@alsa-national.org.

 

New Gene Changes Associated with ALS 

New information on gene changes in people with ALS was reported this month in the Annals of Neurology. Anne-Dort Sperfeld, M.D. and colleagues at University of Giessen in Germany published on a new change in the gene responsible for juvenile onset ALS. The new mutation in the ALS2 gene was in a patient in Turkey, and the change is also present in his unaffected family members: his two brothers and each of his parents. Progression of the man’s disease is more rapid than in other patients with this form of ALS reported to date.  (More Info)

Another mutation was reported to be associated with ALS; in this instance in a gene for the protein dynactin that is involved in moving materials throughout nerve cells. This gene change, in the p150 subunit of the protein, was identified in a family with members who have both ALS and frontotemporal dementia, as reported by Albert Ludolph M.D. and colleagues at the Jewish Hospital in Berlin. (Further details will be presented at the ALS/MND meeting in Dublin in December.)  (More Info)

 

ALS2 Mutation Produces Subtle Change in Mouse

 The mutation responsible for a juvenile onset version of ALS has proven difficult to study in the lab as mutations in the gene that produce the disease in people do not give obvious outcomes in research animals. NIH investigator Huaibin Cai, Ph.D. and colleagues working with Philip Wong, Ph.D. and colleagues at Johns Hopkins published in the August 17 online Journal of Neuroscience that the mutation in the ALS2 gene do not kill motor neurons outright but do make them more susceptible to oxidative stress. The mice also showed age related effects on motor aspects of maze learning and anxiety.  (More Info)

 

Components of Cell Death Pathway Possible Targets for ALS Therapy

What goes on within cells to produce the destruction of ALS is revealed in studies of the process of cell death in lab grown cells bearing the mutated copper-zinc superoxide dismutase (SOD1) enzyme linked with some inherited forms of the disease. The enzymes called caspases, numbered 9, 3, and 8, play an important part in orchestrating cell death in the presence of mutant SOD1 and could be therapeutic targets, according to findings by Pamela Shaw, M.D. at the University of Sheffield, U.K. and collaborators who published in the October 31 issue of Neuropathology and Applied Neurobiology. The researchers confirmed the importance of these particular caspases in mice with the mutation.  (More Info)

 

Mix of Messages to Motor Neurons Changes in SOD1 Mice

In the mouse with a mutation in SOD1 that recreates many of the symptoms of ALS, the motor neurons that die show changes in their ability to register incoming messages, according to findings published in the October issue of Neurobiology of Disease by Burkhard Schütz, Ph.D. at the Institute for Anatomy and Cell Biology in Marburg, Germany. The motor neurons lose the molecules that assist in receiving excitatory messages but keep those that mediate inhibition of the motor neurons. These molecular signs suggest a change in the balance of messages received at the time that symptoms are evident in the mice at 110 days of age.  (More Info)

 

Brain Responses Differ in Sporadic, Inherited ALS

Researchers have detected a difference in the brain response to a slight electrical current sent through the skull as a test of function in patients with an inherited form of ALS caused by a known mutation as compared to patients with sporadic ALS that does not run in the family. As published in the September issue of Journal of Neurology, Neurosurgery, and Psychiatry, the response of the brain to the electrical stimulation was comparatively stronger in patients with sporadic ALS but not in those with a mutation in the SOD1 gene. A marker of inhibitory function was less abundant in those patients with sporadic ALS as compared to those with inherited ALS. The particular mutation studied usually produces a slowly progressing form of ALS, and the researchers, led by Kerry Mills, Ph.D. of Oxford and King’s College Hospital, London, speculated that the cortical function is relatively preserved in the patients with this mutation.  (More Info)

 

ALS Part of a Spectrum of Motor Neuron Disorders

As reported at the ALSA sponsored workshop on frontotemporal dementia and ALS this past spring, Canadian researcher Ian Mackenzie, M.D. of the University of British Columbia, Vancouver, is proposing that ALS is part of a spectrum of motor neuron damage. The tissue changes of the motor neuron disorders are abnormal clumps of protein that are marked by ubiquitin, a molecular tag that allows the cell to dispose of material properly.  The study was published in the August issue of the Journal of Neuropathology & Experimental Neurology.  (More Info)

 

Care by a Multidisciplinary Team Improves ALS Quality of Life

 Dutch researchers published findings in the October issue of Neurology that they presented earlier this year at the meeting of the American Academy of Neurology on the improved quality of life in patients with ALS cared for by a team of physicians and therapists that see at least six cases of ALS yearly. Leonard Van den Berg, M.D., Ph.D. of the University Medical Center, Utrecht and colleagues found that those patients had higher scores on mental health and social functioning as revealed by questionnaires.  (More Info)

 

Gene Therapy Delivers Protection to Lab Grown Motor Neurons

ALSA-funded investigator Nicholas Boulis, M.D. and colleagues at the Cleveland Clinic published on a means to enhance the survival of motor neurons by interrupting the process of programmed cell death called apoptosis. As reported in the August issue of Muscle Nerve, the investigators engineered motor neurons growing in the lab to produce an abundance of a protein that responds to the transmitter glutamate by turning down the rate of apoptosis. These motor neurons were able to resist the effect of glutamate so that the process of apoptosis was not engaged. That is, more of the motor neurons survived the glutamate challenge. The gene therapy, delivering the Bcl (X)L gene, might be an avenue towards a new treatment for ALS, the researchers suggested.  (More Info)

 

Heat Shock Protein 70 Helps Motor Neurons

Researchers at Wake Forest University in North Carolina led by Carolanne Milligan, Ph.D. confirmed and expanded on the importance of a factor that cells make when stressed in assuring survival of motor neurons. As published in the October Journal of Neuroscience, the heat shock protein 70 (Hsp70) is not only able to help motor neurons survive in lab dishes when deprived of other helper molecules but is apparently secreted by muscle cells and by the supportive astrocytes that surround motor neurons. The use of this factor to aid motor neurons must be further studied to assess its potential.  ALSA funded investigations are continuing to examine the role of Hsp70 and other heat shock proteins as therapeutic targets.  (More Info)