Parkinson’s disease begins with degeneration of dopaminergic neurons within the substantia nigra pars compacta, but the cascade quickly recruits cholinergic and cerebello-thalamo-cortical networks. These circuit-wide disruptions explain why gait, balance, cognition, and autonomic regulation can deteriorate even when motor tremor appears well controlled.
Protein misfolding, mitochondrial stress, lysosomal dysfunction, and immune signaling—including genes such as BST1, SYT11, TMEM175, and GRN—activate selective vulnerability across the basal ganglia. Our models incorporate these molecular signatures alongside imaging-derived biomarkers.
Early-stage motor symptoms often respond to levodopa/carbidopa (immediate or extended release), dopamine agonists, and MAO-B inhibitors such as rasagiline, selegiline, or safinamide. Rytary® smooths motor control, while add-on safinamide extends “ON” time.
Complex fluctuations may require enteral Duopa® gel, continuous levodopa/carbidopa infusion (Vyalev™, FDA cleared 2024), or subcutaneous apomorphine (Onapgo™, 2025). Neuromodulation via deep brain stimulation (STN/GPi) remains a cornerstone.
MR-guided focused ultrasound has progressed from unilateral to staged bilateral procedures, with FDA clearance in July 2025 for select centers. It offers incisionless tremor relief and reduced dyskinesia for advanced disease.
SSRIs/SNRIs effectively address depression and anxiety without worsening motor scores. Melatonin or clonazepam mitigate REM sleep behavior disorder, while tailored tapering of dopamine agonists manages impulse-control disorders alongside behavioral therapy.
Orthostatic hypotension starts with hydration, salt, and compression, escalating to droxidopa or midodrine. Botulinum toxin injections relieve sialorrhea, polyethylene glycol is the preferred first-line osmotic laxative, and mirabegron offers bladder control with minimal cognitive burden.
These interventions are powerful, yet they are prescribed largely on population averages. Our progressive agents learn which combination, sequence, and timing work best for each individual patient profile.
The following articles summarize the technical underpinnings of our biomarker extraction and modeling efforts:
