Older adults with greater variability in gait characteristics related to step length and walking speed are more likely to fall, especially after stroke. Recent evidence has suggested that C-C chemokine receptor 5 (CCR5), an established factor involved in immune processes and neuromodulation, may be a promising target for post-stroke recovery. In rodents, CCR5 knockdown was shown to promote motor recovery and increase axonal sprouting after stroke. In humans, post-stroke patients with the CCR5-Δ32 mutation have improved cognitive and motor recovery.
A newly published study by Molad and colleagues investigated the relationship between gait variability and CCR5-Δ32 carrier status. The findings are based on a large prospective cohort of post-stroke patients (Tel Aviv Brain Acute Stroke Cohort; TABASCO) with gait and NeuroTrax computerized cognitive assessment at admission, 6, 12, and 24 months. Analysis was for 335 patients with both gait and CCR5-Δ32 data. The researchers found lower variability and higher speed at 6 and 12 months for carriers vs. non-carriers, even after adjustment for age, gender, education, ethnicity, and stroke severity. This was also true when patients performed a dual (concurrent) task. Notably, lower stride time variability during the dual task was associated with better cognitive function, with a stronger correlation for CCR5-Δ32 carriers than non-carriers, who had higher variability and lower cognitive scores.
This study is the first to report that carriers of a naturally occurring loss-of-function mutation (CCR5-Δ32) show better gait at 6 and 12 months post-stroke that is similar to healthy older individuals. Greater gait variability among non-carriers may be a predictive marker for falls and cognitive decline. Indeed reciprocity between gait variability and cognitive scores suggests the presence of cognitive-motor interactions. The work builds on previous results from the same cohort showing a relationship of CCR5-Δ32 carrier status with cognitive deterioration and depression in humans, as well findings of a correlation with motor function in mice. The investigators posit that CCR5-Δ32 may be a promising molecular target for intervention by reducing inflammatory response. Recently, they initiated a phase 2 clinical trial to examine the safety and efficacy of Maraviroc, a CCR5 antagonist, in post-stroke cognitive impairment; NeuroTrax is an outcome.
Full text (open access):
Molad, J., Hallevi, H., Seyman, E., Rotschild, O., Bornstein, N.M., Tene, O., Giladi, N., Hausdorff, J.M., Mirelman, A., and Ben Assayag, E. (2022). CCR5-Δ32 polymorphism – a possible protective factor from gait impairment among post-stroke patients. European Journal of Neurology. PMID: 36380716