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Beatrice Bowlby
Feeling sluggish after a summer sojourn to a different time zone? A novel cell therapy designed to regulate circadian rhythms could be just the ticket.
When we travel across the world or take on shift work in the early hours, our circadian rhythms can get out of whack. A new cell therapy, currently being tested in preclinical models, may be able to help resynchronize the body’s internal clock. Created by researchers at Rice University (TX, USA) and Northwestern University (IL, USA), it involves engineering cells to continuously produce the metabolic hormone leptin, and could set us on the path to finally beating jet lag.
Metabolism and circadian rhythms are closely linked, although the mechanisms underpinning this connection aren’t fully understood. Previous research has demonstrated that diet composition and the timing of food intake affect the coordination of circadian rhythms across tissues, suggesting that metabolic signaling molecules, such as leptin, may be a promising target for therapeutically correcting an off-kilter body clock.
Engineered cell therapies that can be used to produce and deliver bioactive proteins in situ offer scientists a way of achieving this. The current study developed injectable leptin ‘factories’, which continually produce leptin independent of feeding time or diet, to help facilitate the realignment of circadian rhythms following a phase shift.
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The researchers used a piggybac transposon system to engineer human retinal pigment epithelium cells to express leptin and encapsulated them in alginate via electrospraying to provide protection from the immune system. The cells were then subcutaneously injected into C57BL/6 mice, and analysis of blood samples via human leptin ELISA revealed that leptin was elevated for over a day and remained detectable for 48 hours, well beyond when recombinant leptin would be degraded.
The team then injected the capsules into mice that had been kept on a consistent 12-hour light–dark schedule that was disrupted by either a 4-hour delay or advance – aka mice with an altered circadian rhythm. Their activity was monitored for 7 days, after which the time it took for their body clock to readjust was calculated manually. This demonstrated that the cell therapy accelerated the animals’ ability to adapt to both phase delays and phase advances.
To assess their approach in a model closer to our own species, the researchers also injected two cynomolgus macaques. Leptin showed similar pharmacokinetics in non-human primates as it did in mice, increasing in serum then becoming undetectable by days 3–7.
Meanwhile, capsule administration in animals experiencing 6-hour schedule shifts was found to be safe and had no demonstrable effects on sleep. Implants tracking core body temperature, heartrate and activity – indicators of circadian alignment – showed that the therapy effectively reduced the synchronization time by around 1 day.
“The fact that we observed similar effects in both rodents and non-human primates suggests that the underlying biology may be conserved across species,” commented Fred Turek (Northwestern), a senior author on the study.
Overall, the findings highlight the potential of this novel therapy as a treatment for circadian dysregulation, offering hope for anyone suffering from jet lag or adjusting to a new work timetable.
“This work provides further evidence that metabolic pathways can be harnessed to influence circadian biology,” concluded Jonathan Rivnay (Northwestern), another senior author. “More broadly, it demonstrates how engineered cell therapies can be used to deliver biologically active molecules in ways that would be difficult to achieve through conventional dosing.”
The post How to beat jet lag: could a new cell therapy be the answer? appeared first on BioTechniques.
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