Proposal to NASA: Investigating the Use of IV Lecanemab in Rats in Microgravity to Remove Amyloid Beta Plaque with and without Ultrasound to Open the Blood-Brain Barrier and its implications for Astronauts on long duration missions to Mars

Proposal to NASA: Investigating the Use of IV Lecanemab in Rats in Microgravity to Remove Amyloid Beta Plaque with and without Ultrasound to Open the Blood-Brain Barrier and its implications for Astronauts on long duration missions to Mars.

By David Barckhoff University of Pittsburgh

This proposal outlines a research study to investigate the efficacy of intravenous (IV) lecanemab in reducing amyloid-beta (Aβ) plaque in rats exposed to microgravity, both with and without focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). The study aims to assess the implications of these findings for astronauts undertaking long-duration missions to Mars, where microgravity exposure and potential neurodegenerative risks are significant concerns.

Background and Rationale

Long-duration space missions, such as those to Mars, expose astronauts to unique physiological stressors, including microgravity, radiation, and altered circadian rhythms. Emerging research suggests that prolonged exposure to microgravity may contribute to neurocognitive deficits and potentially accelerate neurodegenerative processes.[1] While the exact mechanisms are still being elucidated, changes in cerebral blood flow, intracranial pressure, and oxidative stress in microgravity environments are hypothesized to play a role in brain health.[2]

Amyloid-beta (Aβ) plaque accumulation in the brain is a hallmark pathology of Alzheimer’s disease (AD) and is associated with cognitive decline.[3] Recent evidence indicates that neuroinflammation and impaired waste clearance mechanisms, which can be exacerbated by stress and environmental factors, may contribute to Aβ pathology.[4] Given the unique stressors of spaceflight, it is plausible that astronauts could be at an increased risk for accelerated Aβ accumulation or impaired clearance.

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I noticed you shared direct links to your prompt on iask. Some of the references there seem to be hallucinations, so I’d be cautious with that platform, as it isn’t reliable.

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Hi @navyfiremedic610 I am just starting a new lecanemab study in mice and have lots of thoughts on this. First FUS is not required, to open BBB for lecanemab and may be more harmful to the rodent than not. Second, although you are correct in terms of risk for neurodegeneration, mice and rats do not develop AB accumulation from stress alone or TBI, they have to be genetically modified accordingly. But I do love that we are on the same page about risk of AD and space flight and would be happy to talk over this idea more if you want to email or DM me!

Thank you. You can email me at navymedic610@yahoo.com dab481@pitt.edu

IV lecanemab administration was used in 26 humans with and without ultrasound. The Ultrasound was more effective in delivering the medication across the BBB than without US. Should be beneficial for Astronauts traveling to and from Mars.

The Amyloid-beta would be injected into the rats while on-board the International Space Station and while on Earth to test the efficacy of the IV Lecanemab administration in reducing or eliminating the Amyloid-beta with and without ultrasound. It should open the BBB better.

I see your re trying to work through the problem. However, I think you should read more on PubMed (not AI) about amyloid seeding protocols, the most common side effects of lecanemab on earth (huge implications for spaceflight), and the potential concerns with FUS in microgravity, and the potential for BBB disruption in space flight within FUS. Then maybe we can discuss.