• The Future of Targeted Gene-Based Therapies and Biomarkers in Parkinson’s Disease”
  • Armina Barahmand,1 Maryam Aschari,2,*
    1. Department of medical laboratory , TeMS.C., Islamic Azad University, Tehran, Iran
    2. Department of medical laboratory , alborz University of medical science , karaj, Iran


  • Introduction: Parkinson’s disease (PD) is defined by progressive motor impairment and a variety of non-motor disturbances, primarily resulting from the degeneration of dopaminergic neurons and the buildup of alpha-synuclein. The disease emerges through a combination of genetic predispositions and environmental exposures. With projections indicating that the number of patients may double by 2040, there is a pressing demand for therapies that can modify disease progression as well as for accurate biomarkers. Importantly, the two fields are closely connected: biomarkers can enable early detection and intervention, while effective treatments require reliable tools for patient classification and monitoring.
  • Methods: Research has largely focused on three main genetic targets in PD. Alpha-synuclein (SNCA) aggregation plays a central role in pathology, and therapeutic strategies include antisense oligonucleotides, aggregation inhibitors, and immunotherapies—some of which are undergoing phase I–II trials. Mutations in LRRK2, especially G2019S, represent the most frequent genetic cause of PD. Therapies in development, including kinase inhibitors and antisense oligonucleotides, have already entered clinical testing with promising results. Another major genetic risk factor is GBA1 mutations. Investigational therapies range from gene therapy and small-molecule chaperones (such as ambroxol and LTI-291) to substrate reduction drugs like venglustat. Together, these approaches emphasize the interconnectedness of lysosomal, synaptic, and immune pathways in PD pathogenesis.
  • Results: The search for reliable biomarkers continues to be a significant challenge. Biofluid analyses (spinal fluid, blood, saliva, urine) have provided valuable insights into alpha-synuclein variants, LRRK2 phosphorylation, and glucocerebrosidase activity, with exosome-derived markers showing particular promise. Imaging techniques such as DAT-SPECT and advanced MRI assist with diagnosis and monitoring, while electrophysiological and molecular tools add complementary perspectives. Despite these advances, no single biomarker currently offers sufficient accuracy for routine use. A combined, multi-modal approach will likely be necessary for effective diagnosis and patient tracking.
  • Conclusion: At present, PD still lacks both disease-modifying therapies and validated biomarkers. Nonetheless, therapeutic efforts targeting alpha-synuclein, LRRK2, and GBA1 are advancing rapidly, and biomarker research is expanding through fluid-based assays, exosomal analyses, and imaging techniques. Moving forward, studies must prioritize patient subgrouping, sex-specific effects, and the integration of biomarker use with treatment strategies. The convergence of genetic and idiopathic pathways provides optimism that upcoming years may deliver breakthroughs in both PD treatment and diagnosis.
  • Keywords: Biomarkers Parkinson’s disease LRRK2, GBA1