Guidelines for preclinical animal research in ALS/MND: A consensus meeting

Abstract

The development of therapeutics for ALS/MND is largely based on work in experimental animals carrying human SOD mutations. However, translation of apparent therapeutic successes from in vivo to the human disease has proven difficult and a considerable amount of financial resources has been apparently wasted. Standard operating procedures (SOPs) for preclinical animal research in ALS/MND are urgently required. Such SOPs will help to establish SOPs for translational research for other neurological diseases within the next few years. To identify the challenges and to improve the research methodology, the European ALS/MND group held a meeting in 2006 and published guidelines in 2007 (1). A second international conference to improve the guidelines was held in 2009. These second and improved guidelines are dedicated to the memory of Sean F. Scott.

Fingolimod: A Disease-Modifier Drug in a Mouse Model of Amyotrophic Lateral Sclerosis

“…The survival time was considered as the actual age of death or the time (defined as end stage), when mice were sacrificed because of the loss of the ability to right themselves within 30 s after having been placed on their sides, according to established guidelines for drug testing in ALS mouse models [27]. WT animals were sacrificed when the last transgenic mice died.…”

“Preconditioning” with latrepirdine, an adenosine 5′-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1G93A mice

“…These mice are congenic on the C57Bl6 background and carry a high copy number of the G93A mutant SOD1 transgene. Mice were housed in cages of between 3-5 mice and all mice for this study were age, gender and litter matched according to specific ALS pre-clinical trial guidelines (Ludolph et al 2010 SOD1 G93A mice were given Latrepirdine (1 g/kg/day I.P. injection) or PBS vehicle commencing at PND 70 until PND 120.…”

“…For lifespan and motor function assessment, animals were age-, gender-and litter-matched in accordance with recent ALS guidelines for the generation of preclinical data (Ludolph et al 2010). Tests were performed blind by a single observer, twice weekly with a day interval between testing.…”

“…Motor function tests included Rotarod (Stoelting, Illinois, USA), grip strength (Ugo, Basile, Italy) and stride length measurements (Gurney et al 1994). End stage of ALS disease progression was determined by the extreme weakening of hind limbs and loss of righting reflex within 30 seconds of when mice were placed on their back (Ludolph et al 2010).…”

“…At PND 120, symptoms have progressed and there is noticeable hind limb weakness. End stage in SOD1 G93A transgenic (tg) mice is determined when animals are unable to 'right' themselves after 30 seconds on their back, known as the righting reflex test (Ludolph et al 2010). In order to examine AMPK activation across ALS disease progression, we analysed AMPK activation in the lumbar spinal cord homogenates from non-transgenic (non-tg) and tg mice at various timepoints (PND 50, PND 70, PND 90, PND 120 and end stage).…”