Also: Amyotrophic Lateral Sclerosis & Gait in Mice in JNER.
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Early Changes in ALS Mice Pave Way for Testing Candidate Drugs
June/July, 2005
Researchers at Mouse Specifics and The Jackson Laboratory, funded in part by The ALS Association (ALSA), recently demonstrated differences in treadmill gait in advance of the appearance of overt symptoms in a mouse model of ALS. Our findings were published in the May 2005 issue of Muscle and Nerve. The early and subtle gait differences could help scientists to target crucial aspects of ALS much sooner in the disease process using mice that model the
disease.
Mouse Specifics developed a gait imaging system that generates digital paw prints of mice and rats walking on a transparent treadmill belt. A patent on the technology was recently awarded to The CuraVita Corporation, which has licensed the technology to Mouse Specifics for sale and distribution. Comprehensive software developed by Mouse Specifics generates gait signals that rapidly provide quantitative dynamic indices of gait. A high-speed digital camera and recorder enable rapid acquisition, processing, and storage of gait data from hundreds of studies.
Patients with ALS often are not diagnosed until advanced stages of the disease. New drugs may improve outcomes if they are administered sooner. "Gait disturbances are characteristic of patients with ALS," says Tom Hampton, Mouse Specifics CEO and a biomedical engineer who pioneered the gait imaging technology used in the study. "Early detection of gait disturbances may result in earlier treatment."
The value of the gait imaging technology is becoming increasingly recognized with new findings in mouse models of Down's syndrome, Parkinson's disease, and dystonia. This most recent study of a gait in the new congenic B6 SOD1 mice brings to 10 the number of publications by Mouse Specifics applying its DigiGait maging technology. The Muscle and Nerve study is the 4th publication from Mouse Specifics acknowledging the support of the ALSA.
Ajit Kale from Mouse Specifics and collaborators from The Jackson Laboratory studied mice bearing a mutation analogous to one responsible for some inherited cases of human ALS. These mice have been shown to exhibit symptoms analogous to those experienced by patients with ALS. The mutation
is in the enzyme copper-zinc superoxide dismutase 1 (SOD1).
Mouse Specifics created the gait analysis system as part of an ALSA funded program (see http://www.alsa.org/research/grant.cfm?id=191). This recent study used a different strain of ALS mice than previously available, with less genetic variability. Thanks to the quantitative measures of “walking” made possible by the technology, this study reports the earliest functional phenotype in a mouse model of ALS. Gait differences were detected in mice as young as 8 weeks of age. More obvious manifestation of ALS, such as tremor in the hind limb, appear at ~20 weeks of age. Advancements in the imaging hardware and analyses software made by Mouse Specifics may provide opportunities to detect even earlier changes if younger ALS mice are studied.
