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Lithium Microdoses: a New Way Forward in the Treatment of Alzheimer’s Disease?

Posted on 27 January 2020

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For some time, lithium (currently prescribed for some mood disorders) has been regarded as a potential protective agent for Alzheimer’s disease. It is able to modulate several disease mechanisms such as inflammation, oxidative stress and mitochondrial function.

Unfortunately, the treatment of Alzheimer’s disease with lithium has been controversial. Past studies investigating the effectiveness of lithium have been inconsistent in their approaches, making it difficult to compare results. Lithium also carries a number of serious side effects in high doses, meaning it cannot be used for long term treatment.

A study published in the Journal of Alzheimer’s Disease found that lithium treatment was able to halt and reverse progression of Alzheimer’s disease in transgenic rat models. What makes this study particularly significant, however, was that this affect was achieved with doses hundreds of times lower than currently prescribed for mood disorders. This was thanks to new formula, NP03, a microemulsion in which lithium is encapsulated by polar molecules such as phospholipids and surfactant. This increases the amount of lithium reaching the central nervous system, allowing the same effect to be achieved with significantly lower doses.

Lithium contained within a microemulsion droplet

Microdose treatment using this formula offers the potential to eliminate some of the adverse effects of lithium treatment, allowing it to be used long term in conjunction with other therapies. However, clinical trials in humans have yet to be launched, and animal models of dementia compare poorly with human disease. There is therefore always the possibility that NP03 will not be viable for use in humans.

From a practical point of view our findings show that microdoses of lithium in formulations such as the one we used, which facilitates passage to the brain through the brain-blood barrier while minimizing levels of lithium in the blood, sparing individuals from adverse effects, should find immediate therapeutic applications. While it is unlikely that any medication will revert the irreversible brain damage at the clinical stages of Alzheimer’s it is very likely that a treatment with microdoses of encapsulated lithium should have tangible beneficial effects at early, preclinical stages of the disease.

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    NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats: DOI: 10.3233/JAD-190862

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