Precision Dopaminergic Treatment in a Cohort of Parkinson's Disease Patients Carrying Autosomal Recessive Gene Variants: Clinical Cohort Data and a Mini Review.

INTRODUCTION

Parkinson's disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce.

METHODS

Demographic and treatment data of a cohort of PD carriers of recessive genes (nine homozygous or compound heterozygous carriers, four heterozygous carriers, and three biallelic carriers) were evaluated.

RESULTS

The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152-1810) in carriers and 765 ± 96.6 (range 660-850) in carriers. The majority responded to low/moderate doses of levodopa. The response to dopamine agonists (DAs) was often favorable both as initial and longitudinal therapy. In total, 8/13 and 1/3 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs.

CONCLUSIONS

In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any levodopa treatment decades after disease initiation. DAs or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments, will be further discussed.