Mouse Specifics, Inc. is serious about providing a useful quantitative instrument to the research community to advance better understanding of animal models of human movement disorders. DigiGait is the most widely published treadmill gait analysis system available . The ability to walk and run is coveted by humans. In particular patients with Parkinson’s disease, multiple sclerosis, stroke, and spinal cord injury all hope to maintain or regain their mobility.
Quantitative assessment of walking, or gait analysis, helps to identify and treat the causes of movement disorders. Mr. Reza Baluchi so enjoys walking and running that he has devised a bubble to enable him to walk - on water - from Florida to Bermuda. CNN reports that the Coast Guard, however, recently ordered Mr. Baluchi not to depart "because your vessel and the conditions under which you are attempting to complete your voyage to Bermuda are unsafe”. Gait analysis of Mr. Baluchi walking inside the bubble would be difficult, and probably pointless. Unfortunately, some reports of gait analysis in animal models of human disorders are also dangerous, and pointless.
The DigiGait Imaging System, on the other hand, is the most meaningful treadmill gait analysis instrumentation available. DigiGait has been applied to the wide area of study related to walking in animal models, such as Huntington’s disease, cerebral palsy, amyotrophic lateral sclerosis, Parkinson’s disease, and arthritis, to name a few. The abounding publications using DigiGait include numerical gait data, reflecting the posture and kinematics of the animals studied. Mouse Specifics, Inc. vigilantly studies the science and medical literature for reports about gait analysis, gait metrics, and novel gait findings, in our effort to make DigiGait as useful and applicable as possible.
It is disconcerting, then, to read erroneous and misleading publications that purport to describe gait in animal models. A recent abstract, for example, describes how “gait analysis” demonstrated that a novel apoA-I mimetic peptide improved functional recovery in a mouse model of hind limb ischemia (1). Closer reading of the manuscript goes into great detail about the “gait analysis”, based on watching mice voluntarily walk across a glass plate. The only readout from the “gait analysis” was the animal’s speed. No useful information about how the potentially useful compound affected the posture and kinematics of the ischemic and non-ischemic limb were reported. It is quite possible that the technique employed is not sensitive enough to provide detailed quantitative information about the more subtle effects of limb ischemia because a) the animals voluntarily walked a variety of speeds; b) the study lacked means to ensure that control and ischemic animals walked the same speed. The readout, in this case simply the speed of the animals, could reflect the behavior, mood, or motivation of the animals to walk across the glass plate. It is disingenuous to conclude that “gait analysis” was able to demonstrate that functional recovery was different between groups. It might be acceptable to conclude that animals treated with the novel apoA-I mimetic peptide moved faster (1), but faster movement can result from a wide variety of factors.
Another recent publication reports that gene therapy to block dorsal striatal p11 production improves motor function and dyskinesia in parkinsonian mice (2). Parkinson’s disease in humans is characterized by cardinal gait disturbances, such as reduced stride length, increased stride frequency, and increases in gait variability metrics, such as swing time and stride length variability. Though this study about systemic p11 inhibition purports to analyze gait, no quantitative gait analysis is provided. The speeds cited on the treadmill of 3, 5, and 7.5 cm/s are extremely slow walking speeds for mice. A speed of 3 cm/s is almost imperceptible, and allows a mouse to do a variety of things instead of walking, including rearing, climbing, turning, or escaping [see video clip of mouse on treadmill belt moving at speed of 3 cm/s, 7.5 cm/s, 17 cm/s, and 34 cm/s]. “20 s of recorded running at 7.5 cm/s on the moving treadmill” as reported by the authors are not a likely occurrence, without some sort of disclaimer about how the “running was performed” and how the other motor actions are delineated from the animals “gait”. Note how in these videos below, that at 3 cm/s, and 7.5 cm/s, speeds that are much too slow for “walking”, the animal has ample opportunity for hesitating, stopping, turning, and rearing. Rather, the gait analysis instrumentation is widely more useful if the animal is enabled to walk speeds relevant to the natural inclinations of the animals, such as 34 cm/s and beyond.
There is something not quite the same about the walking of the man inside the bubble, who has twice been rescued by the coastguard, and the walking of a man who may be exhibiting early signs of multiple sclerosis. I personally believe Mr. Baluchi’s commitment to walking on water and his ingenuity are laudable, though to analyze his gait while walking inside his bubble as it bobs along the water would not provide anything more than what we already know: 1) there are better ways to get to Bermuda; 2) experts have come twice to his rescue. If you are considering serious gait analysis of your animal models of human disease, please contact the DigiGait experts at Mouse Specifics!
References
1. Takata K, et al. The ApoA-I mimetic peptide FAMP promotes recovery from hind limb ischemia through a nitric oxide (NO)-related pathway. Int J Cardiol. 2016 Mar 15; 207:317-25. Abstract Request Reprint
2. Marongiu R et al. Gene therapy blockade of dorsal striatal p11 improves motor function and dyskinesia in parkinsonian mice. Proc Natl Acad Sci U S A. 2016 Feb 2;113(5):1423-8. Abstract Request Reprint