ALS Research Journal News - March 2007

Gene Findings and ALS: Initial Results, Tantalizing Hints

Genome analysis data obtained for sporadic ALS and neurologically normal control samples at the National Institute of Aging and colleagues are detailed in the Lancet Neurology publication.
http://www.ncbi.nlm.nih.gov/pubmed/17362836

Traynor and collaborators have also reported in BMC Neurology that progranulin mutations are not common in ALS.
http://www.ncbi.nlm.nih.gov/pubmed/17371905

A collaboration led by Traynor also reports in the Journal of Neurology, Neurosurgery, and Psychiatry an analysis of a candidate gene on chromosome 9 in the region linked with ALS, but no definitive conclusion could be reached.
http://www.ncbi.nlm.nih.gov/pubmed/17166276

Garth Nicholson, M.D., Ph.D., and collaborators at ANZAC Research Institute, Concord Hospital, Sydney, Australia, reported a new gene location for motor neuron disease on chromosome 7 and narrowed the area to search for mutation. The family studied has affected individuals with a disease described as a juvenile ALS and distal hereditary motor neuropathy. Findings are published in Human Genetics.
http://www.ncbi.nlm.nih.gov/pubmed/17354000

Microglia Behave Abnormally in ALS

The behavior of microglia in the rat with mutation to copper, zinc superoxide dismutase (SOD1), is abnormal even prior to symptoms, according to a detailed histology study published in the Journal of Neuroinflammation. Investigators at the University of Florida in Gainesville, led by Wolfgang Streit, Ph.D., show that with symptom onset the glia have formed multinucleated giant cells by fusing together evident in many areas of the spinal cord and brain stem. Apoptosis did not seem to be involved in this abnormal glial activity.
http://www.ncbi.nlm.nih.gov/pubmed/17328801

Astrocytes Support the Development of Neurons Derived from Human Embryonic Stem Cells

Su-Chun Zhang, M.D., Ph.D., at the University of Wisconsin, Madison, and colleagues reported in the Journal of Neuroscience that the neurons generated from human stem cells in the lab depend on surrounding astrocytes to develop. Apparently the astrocytes are helping the neurons through the contacts they make, which allow the neurons to begin to generate their normal electrical signals to communicate to the neighbor neurons.
http://www.ncbi.nlm.nih.gov/pubmed/17376968

Imaging Astrocytes in ALS

Astrocytes accumulate in ALS as suggested by imaging results that demonstrate differences between ALS patients and other people, published in the Journal of the Neurological Sciences. Swedish researchers working with Håkan Askmark M.D., at University Hospital, Uppsala, attempted to show astrocytes selectively by using a radioactive labeled drug, deprenyl, which attaches to the enzyme, called MAO-B, found primarily in the astrocytes thereby showing these cells selectively. How selective the imaging is for these supportive cells implicated in ALS remains to be determined by future studies.
http://www.ncbi.nlm.nih.gov/pubmed/17346749

Imaging in ALS Show Early, Widespread Change

Italian researchers reported imaging studies on 25 patients early in ALS progression, as compared to healthy controls, finding differences that demonstrate the disease affects wide areas in the brain, even early in the disease. The findings in Human Brain Mapping were published by Massimo Filippi, M.D., and colleagues at the Ospedale San Raffaele, Milan, Italy.
http://www.ncbi.nlm.nih.gov/pubmed/17370339

Histology, Clinical Picture, of ALS and Cognitive Change

Dutch researchers at Erasmus University published in Brain on individuals in families with inherited frontotemporal dementia (FTD) with or without motor neuron disease. They found TDP-43 protein in deposits in five brains available from eight patients from a total of six families whose clinical details were available. Three had motor neuron disease as the presenting problem while the other five had FTD and then motor symptoms. Glial inclusions in one brain were positive for TDP-43 as well in the basal striatum area of the brain. The findings, reported by John van Swieten, M.D., Ph.D., and colleagues, point to the wide spectrum of the disorder.
http://www.ncbi.nlm.nih.gov/pubmed/17360763

Caregiver Burden in ALS

In Neurology a report shows that on average, ALS patients do not report increased depression as their disease progressed over a nine month period, but the caregivers perceive stress and burden of care. The findings of the team led by Italian investigator Adriano Chio, MD, with the University of Torino, may reflect acceptance by the patient, or their cognitive impairment, the researchers concluded.
http://www.ncbi.nlm.nih.gov/pubmed/17372127

A report in Neurology by investigators at the Mayo Clinic, Rochester, Minn., suggests referral bias can arise if survival time is used as a measure of ALS progression. Clinical trial planners should take into consideration that patients who choose a multidisciplinary or tertiary care clinic may have differences in disease progression that can skew survival data, Eric Sorenson, M.D., and colleagues concluded.
http://www.ncbi.nlm.nih.gov/pubmed/17310031

Japanese Researchers Model Potential Therapeutics on Ubiquitin Enzyme

Dorfin is a ubiquitin ligase that breaks down mutant SOD1 proteins. According to findings published in Neurobiology of Disease, Nagoya University investigators working with Gen Sobue, M.D., have made molecules to mimic this usually short lived enzyme. The result was more rapid destruction of SOD1 mutant protein by the ubiquitin system that removes cellular trash. Cells were protected in lab dishes by the compounds, the investigators reported.
http://www.ncbi.nlm.nih.gov/pubmed/17157513

SOD1 Mutant Rats Show Sex Differences in Disease

Clive Svendsen, Ph.D., and colleagues reported in the Amyotrophic Lateral Sclerosis journal that rats with the SOD1 mutation differ in the symptom onset according to sex, with males showing consistently shorter time to onset. Motor function was impaired earlier as well in males, though both sexes progressed at similar rate. This dimorphism for SOD1 mutation effects is known for mice as well. In people, men are more at risk to develop ALS as well.
http://www.ncbi.nlm.nih.gov/pubmed/17364431

Protein Linked with SOD1 Mutation in Mice

A protein is increased in mice that mimic ALS, even before symptoms appear, according to research by Kenneth Hensley, Ph.D., and colleagues at the University of Oklahoma, Oklahoma City, reported in Biochemistry. The protein is called lanthionine synthase C-like protein, and it is involved with glutathione, a cell scavenging system protecting cells from potentially harmful metabolic products as well as toxins.
http://www.ncbi.nlm.nih.gov/pubmed/17305318

Reviews on Axon Dynamics, Cognitive Change

Lawrence Goldstein, Ph.D., at the University of California San Diego, La Jolla, reviews in Public Library of Science, Genetics insights gained from recent progress in understanding the genetics of axonal transport, the flow of nutrients and needed cell constituents along the nerve fiber, which is implicated in ALS.
http://www.ncbi.nlm.nih.gov/pubmed/17009871

Michael Coleman, Ph.D., of the Babraham Institute, writing in Trends in Neuroscience, discusses how damage in one cell compartment manifests in others, and in the demise of the entire neuron, in many different diseases including ALS. Ways to approach the disease processes in order to discover the sequence of events that will provide targets for new treatments are explored in this review.
http://www.ncbi.nlm.nih.gov/pubmed/17339056

In a review article in Archives of Neurology, Catherine Lomen-Hoerth, Ph.D., and colleagues at the University of California, San Francisco, discuss the decade’s progress in linking cognitive changes in ALS to the changes in frontotemporal dementia and strategies to help diagnose and find new therapies for this wide clinical spectrum.
http://www.ncbi.nlm.nih.gov/pubmed/17353375