Table 3

Potential approaches for disease modification in PD and iRBD

ImmunisationMonoclonal antibodies directed toward the toxic conformations of synucleinSeveral ongoing phase I and II trials of passive and active immunisation (RO7046015, PASADENA trial; BIIB054, SPARK trial)70
Blockers of synuclein misfolding or aggregation NPT088, glycerol phenylbutyrate, squalamine, 71
nilotinib, selective c-Abl
inhibitors,72 epigallocatechin gallate73
Neuroinflammation modifiers
Anti-inflammatoryIbuprofenLower PD risk in people receiving non-steroidal anti-inflammatory agents74; alpha-synuclein increases inflammation
AZD3241 (selective, irreversible myeloperoxidase inhibitor)75 Benefit on microglia brain imaging in a short-term trial in PD 75
AntibioticsDoxycycline, tetracyclineProtective in PD animal models76; Rosacea is associated with higher PD risk, treatment with doxycycline reduces this risk77
Oxidative stressMelatonin (antioxidant) Symptomatic effect in RBD 18
Neuroprotective in various animal PD models78
Glutathione (antioxidant)N-acetylcysteine (glutathione precursor) trial79
Troloxamide-quinone trial (NCT02462603)
Apamin (from bee venom)Protective in a PD mouse model80
IronDeferiprone (iron chelator)FAIRPARKI: small randomised double-blind delayed start trial in treated patients with PD81 SKY and FAIRPARKII ongoing trials
Adrenergic systemBeta-2 adrenergic receptor (B2R) agonistB2R agonists: lower PD risk71; B2R regulates the alpha-synuclein gene82
Modafinil: common and safe stimulant in narcolepsyNeuroprotective in MPTP parkinsonism marmosets and cats83
Some patients with RBD are sleepy 84
Glucagon-like peptide-1Exenatide (antidiabetics)May reduce DA neurons apoptosis85
Glucocerebrosidase activity (GBA mutation)Glucosylceramide synthase inhibitors;
GBA-modifying drugs (ambroxol)
Tailored treatment in GBA mutation carriers or in sporadic PD with low GBA activity (NCT0294182)
GBA mutations in 10% of patients with iRBD 86
Reduce α-synuclein fibrillation and decrease parthenatos cell-death pathwayPoly(adenosine 5′-diphosphate-ribose) polymerase 1 (PARP1) inhibitorsOlaparib, rucaparib, niraparib, talazoparib are all FDA approved for certain cancers
Increasing DA activityNicotineLower PD risk in smokers87
But higher RBD risk in smokers 88
Trial NIC-PD, n=160: ongoing
Lifestyle modifiers
Diet: selective increased consumptionCaffeine (black tea, coffee)Lower PD risk in heavy coffee drinkers89
No lower RBD risk 88
Diet: selective increased consumptionEating edible solanaceae (tomatoes, peppers, potatoes) containing nicotineEpidemiological evidence for lower PD risk when eating these foods90
Diet: selective increased consumptionEating more omega 3 polyunsaturated fatty acidsBut no neuroprotection in mild cognitive impairment (MAPT study)91
Diet: selective decreased consumptionReducing milk consumptionIncreased PD risk when drinking fresh milk92
Diet: selective decreased consumptionAvoid eating tropical fruits/food containing annonacin (soursop)Associated with atypical PD93
RBD in up to 55% of patients with parkinsonism of French West Indies 94
Diet: selective increased consumptionYerba mate teaInverse association between yerba mate consumption and PD in South America95 96
Lifestyle: decreasing exposure (food, air)Avoid exposure to pesticides RBD is more frequent in workers using pesticides 88
PD is more frequent in workers using pesticides
Exercise and physical activityExercise and physical therapyAnti-inflammatory, antioxidant, promitochondrial, trophic and anti-synuclein effects97–99
  • In italics: human trials in PD; in bold: data in iRBD. Most details can be found in a recent review.142 As for lifestyle changes, details can be obtained from a recent review on RBD risk factors.4

  • c-Abl, Abelson non-receptor tyrosine kinase ; DA, dopamine; FDA, Food and Drug Administration; GBA, glucocerebrosidase ; iRBD, isolated rapid eye movement sleep behavioural disorder; MAPT, microtubule-associated protein tau; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PD, Parkinson’s disease; RBD, rapid eye movement sleep behavioural disorder.