ALS Research Forum | To Evaluate Stem Cell Therapies, Think … – ALS Research Forum

Testing stem cell therapies unilaterally?A side-by-side comparison of strength of key muscles may enable scientists to evaluate stem cell therapies for the disease. The approach aims to control for the variability of the disease internally, without historical cohorts and/or the use of a placebo (see Donofrio and Bedlack, 2011; Glass et al., 2016).The biceps and triceps appear to be most reliable muscles to monitor progression in people with ALS according to this analysis (Rushton et al., 2017). [Neural progenitor cells. Courtesy of Nature Cell Biology. Reproduced with permission.]

Motor neurons degenerate in ALS. Why these cells are destroyed remains unclear. Therefore, how to slow or stop this destruction of motor neurons in ALS remains an open question.

In the meantime, a growing number of scientists are turning to stem cells in hopes to promote motor neuron survival in people with ALS and/or reduce their toxicity (see December 2015 conference news). But how to evaluate these strategies in the clinic remains hotly debated.

Now, a research team at Cedar Sinai Medical Center in Los Angeles, California reports that an emerging outcome measure, which involves monitoring muscle strength, may facilitate the evaluation of stem cell therapies for the disease (Rushton et al., 2017). The study, led by Clive Svendsen, found that functional decline of key muscles on the left and right side of people with ALS progressed at a similar rate. The results suggest that at least some stem cell therapies could be evaluated unilaterally by comparing the strength of muscles on the treated and untreated side for each of these muscle groups.

This side-by-side comparison, according to a subsequent power analysis, may enable clinicians to evaluate stem cell therapies for ALS in a smaller sample size without the need for sham surgeries and/or placebo injections.

This unilateral approach is emerging as an alternative to evaluate a growing number of potential neuroprotective strategies for neurodegenerative diseases including ALS (see NCT02943850, NCT02478450; Glass et al., 2016).

The study is published on June 9 in Neurology.

The retrospective analysis, performed in collaboration with Cedar Sinais Robert Baloh, studied the rates of decline of 6 upper and lower muscle groups in nearly 750 people with ALS determined by fixed dynamometry. These longitudinal datasets, previously collected by physical therapist Pat Andres and colleagues, now at Massachusetts General Hospital, capture the decline in strength of key muscles in people with ALS during at least a 16-month period measured by either the TUFTS Quantitative Neuromuscular Exam (TQNE) or more recently, the Accurate Test of Limb Isometric Strength (ATLIS) system (Andres et al., 1986; Shields et al., 1998; Andres et al., 2012.

Analyzing therapies by hand. Meanwhile, Biogen scientists in Cambridge, Massachusetts are turning to hand-held dynamometry to evaluate potential therapies for ALS. The emerging strength-based measure highly correlates with the progressive loss of motor function (ALS-FRS-R) and breathing capacity (FVC) according to a retrospective analysis of 924 people with ALS presented at the 2017 meeting of the American Academy of Neurology (see May 2017 news). And, according to a subsequent side-by-side comparison, these musclesdecline at similar rates. [Image: Douma et al., 2014 under CC BY 2.0 license.]

The study builds on previous work, led by Barrow Institutes Jeremy Shefner in Phoenix, Arizona and Biogens Toby Ferguson in Cambridge, Massachusetts, which found that monitoring the strength of key muscles using hand-held dynamometry is a reliable and reproducible approach to measure progression of ALS in a clinical setting and thereby, may facilitate the evaluation of potential therapies (see May 2017 conference news; Shefner et al., 2014).

Now, Svendsens team is gearing up to evaluate their potential stem cell therapy for ALS. The strategy uses genetically engineered neural progenitor cells (NPCs) to deliver GDNF into the CNS in hopes to protect motor neurons in people with the disease (see April 2017 news; Gowing et al., 2014). The approach is at the phase 1 stage. Stay tuned.