Cure Parkinson’s and Van Andel Institute announce funding for a phase 1 clinical trial of low-dose lithium in Parkinson’s disease

LONDON (May 29, 2024) — Cure Parkinson’s and Van Andel Institute (VAI) are delighted to announce funding for an upcoming phase 1b clinical trial to investigate whether lithium, a drug currently used to treat mood disorders, could be repurposed to slow the progression of Parkinson’s.  

Lithium has a long history of clinical use in bipolar disorder due to its mood-stabilizing effects. In the U.S., it has been approved as a treatment for the condition since 1970 but, more recently, it has started to garner attention from researchers as a possible treatment for Parkinson’s.

“Drug repurposing represents a means of rapidly bringing new treatments to patients by testing agents that we already know a lot about. If low-dose lithium can help slow the progression of Parkinson’s, then this would be an important development for the Parkinson’s community. Cure Parkinson’s is delighted to be supporting this study,” said Cure Parkinson’s Director of Research Simon Stott, Ph.D.

Cure Parkinson’s and VAI will fund the recruitment of 20 participants to the upcoming phase 1b clinical trial of low-dose lithium in Parkinson’s, led by Thomas Guttuso, M.D., at University of Buffalo. This is in addition to 15 people with Parkinson’s already funded by the U.S. National Institutes of Health (NIH), bringing the total cohort size to 35 participants.

“Parkinson’s is an immensely complex disorder that requires an equally sophisticated approach to seeking treatments that slow or stop progression. International Linked Clinical Trials enables us to prioritize medications like lithium that are known to treat other diseases and that may have use in Parkinson’s. This phase 1b trial will be an important step in evaluating lithium’s potential use in impeding disease progression, and we look forward to the results,” said Darren Moore, Ph.D., Chair of VAI’s Department of Neurodegenerative Science and a member of the International Linked Clinical Trials Committee.

Related: Learn more about the International Linked Clinical Trials program ➔

Primarily, the researchers will explore whether lithium affects two biological indicators (or biomarkers) of Parkinson’s progression: 1.) levels of the protein Nurr1 in the blood, and 2.) levels of “free water” in the brain. Biomarkers like these are important because they allow researchers to monitor what is occurring in the brain without directly accessing it.

Nuclear receptor related 1 protein (Nurr1) is a protein that plays a vital role in the creation of new dopamine neurons, the type of cells that are progressively lost in Parkinson’s. Although Nurr1 levels decrease naturally with age, evidence suggests that Nurr1 levels are even lower in people with Parkinson’s. In a 2019 pilot study of lithium for Parkinson’s, low-dose lithium was found to increase Nurr1 levels, which may promote dopamine neuron survival in people with Parkinson’s, therefore potentially slowing disease progression.

Increased levels of free water in the brain, measured via brain imaging techniques, can be used as a marker of dopamine neuron loss in Parkinson’s. Free water refers to fluids in the brain that are not bound in cells. The 2019 pilot study suggested that low-dose lithium may be able to reduce this free water increase in the brain; the new phase 1 study will look to replicate this finding in a larger cohort of people with Parkinson’s.

“Because brain free water is one of our leading disease progression biomarkers in Parkinson’s disease, if this study is able to replicate our earlier findings associating low-dose lithium therapy with reductions in free water, this would support low-dose lithium’s ability to slow Parkinson’s progression and also strongly support further clinical research using this simple and inexpensive therapy. Positive effects on one or more blood-based biomarkers, including Nurr1, would further bolster this research program,” Guttuso said.  

Overall, the trial aims to provide the necessary data to determine whether low-dose lithium should continue to be investigated further for Parkinson’s. Recruitment is anticipated to begin in mid-June.

Why study lithium in Parkinson’s?

Early preclinical data suggests that lithium at very low doses may be protective against the dopamine nerve cell (neuron) loss seen in Parkinson’s. In 2019, Guttuso conducted a small pilot study to test this potential link in people with Parkinson’s. The results suggested that lithium had a positive effect on trial participants. As such, in 2022, low-dose lithium was prioritized by the International Linked Clinical Trials (iLCT) program — a drug development initiative set up in partnership between Cure Parkinson’s and VAI to support the clinical evaluation of drugs with the potential to slow, stop or reverse Parkinson’s progression.

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Research reported in this publication is supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health under award no. UL1TR001412. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders