Saturday, April 20, 2024
4/20/2024
PROJECT SUMMARY Multiple sclerosis (MS), an inflammatory and neurodegenerative disorder of the central nervous system (CNS), is the most common cause of progressive neurologic dysfunction in early to middle adulthood. People with MS are a markedly high risk for sleep disturbance. Estimates of the lifetime prevalence of sleep disturbance in MS reach 50%; sleep disturbance is also associated with excess MS-associated morbidity and diminished quality of life. Despite the high burden of impaired sleep and its contribution to adverse MS outcomes, effective approaches to treat and ameliorate disturbed sleep in people with MS remain poorly understood. Current pharmacologic strategies offer predominantly short-term solutions and may not be ideal for the typically chronic and habitual nature of sleep disturbance in MS. Therefore, there is unmet need to develop safe and effective rehabilitative alternatives to mitigate sleep disturbance in MS. Prior research supports the use of timed bright light therapy (LT) as one such approach for insomnia and sleepiness in those with sleep disorders or other neurologic diseases. Yet, the safety and potential effectiveness of timed LT have yet to be tested in MS. The goal of the proposed study is to conduct a detailed intervention study testing if timed bright LT in people with MS is 1) safe (primary outcome) and 2) potentially effective for reducing sleep disturbance (specifically, reducing insomnia, fatigue and improving sleep efficiency, quantity and quality as secondary outcomes). Furthermore, our study will explore whether LT stimulates a novel subtype of retinal ganglion cells which are central to the regulation of circadian rhythms and sleep. Namely, this subtype, intrinsically photosensitive retinal ganglion cells (ipRGCs), serves as the origin of the retinohypothalamic tract, projects light information to the central circadian pacemaker in the hypothalamus, and, intriguingly, may be impaired in people with MS (as suggested by our preliminary data). Thus, results of these highly innovative exploratory analyses may suggest a candidate mechanism for the observed effect as well as a potential rehabilitative target for improving sleep in people with MS (or in a specific subset of patients). Collectively, this pilot will provide integral preliminary data to support future definitive trials of bright LT as safe, possibly efficacious approach for sleep disturbance in people with MS. Importantly, it will also provide key insight into a potentially intervenable biological target for sleep disturbance in a highly vulnerable patient population.
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