Study Rationale: Polyamines are molecules that show neuroprotective effects, and one of the genes that is mutated in Parkinson’s disease (PD), ATP13A2, regulates cellular polyamine levels. Unpublished work shows that mice with a deficient version of this gene exhibit changes in plasma polyamine levels and benefit from polyamine modulation strategies. To translate these findings to the clinic, we plan to recruit patients carrying pathogenic variants in the ATP13A2 gene for a clinical examination and collection of biosamples.
Hypothesis: We hypothesize that ATP13A2 mutation carriers with PD display altered plasma polyamine levels, which would pave the way for clinical trials to modulate polyamine levels.
Study Design: We will recruit 50 volunteers carrying pathogenic variants in the ATP13A2 gene for clinical examination and collection of biosamples (plasma, urine, cerebrospinal fluid and cells) that we will bank at KU Leuven. We will analyze and report the polyamine levels in these biosamples, and we will prepare follow-up studies of PD markers to study the ATP13A2 disease mechanism.
Impact on Diagnosis/Treatment of Parkinson’s disease: Our findings will contribute to a mechanistic understanding of the ATP13A2 pathology and will facilitate clinical trials to modulate polyamine levels. Because reduced plasma polyamine levels have been observed in people with sporadic PD, our study of ATP13A2 mutation carriers may have value for patient stratification of sporadic PD.
Next Steps for Development: If altered plasma polyamine levels are confirmed in carriers with pathogenic ATP13A2 variants, we will prepare to conduct clinical trials to modulate polyamine levels.