Disease indication
Why the animal models predict symptom relief — and almost nothing else
Disease-modifying: Slow or halt the nigrostriatal degeneration itself. Every model put to this test has so far failed to predict the clinic: strong preclinical neuroprotection, then a null result in patients — ten times over.
No therapy has ever been shown to slow the progression of Parkinson's disease.
Disease-modifying candidates below with a completed readout. One further programme is still running.
A delayed-start or withdrawal design is required to separate symptom masking from true modification — the single largest cost driver.
Larger and longer than symptomatic trials because the effect being measured is a change in slope.
Three standard axes. Toggle the therapeutic goal above and watch only the third column change — that asymmetry is the whole story.
| Model | FaceDoes it look like the disease? | ConstructDoes it arise the same way? | PredictiveSlow progression |
|---|---|---|---|
Every programme below cleared its animal model. None has yet changed the course of the disease in a patient.
| Intervention | Rested on | Reached | Outcome |
|---|---|---|---|
Exenatide UCL / NIHR · GLP-1 receptor agonist | 6-OHDAMPTP mouse | Phase 3 Exenatide-PD3 · 2025 | Failed |
BIIB122 / DNL151 Denali / Biogen · LRRK2 kinase inhibition | LRRK2 G2019S | Phase 2b LUMA · 2025 | Ongoing |
Prasinezumab (PRX002) Roche / Prothena · Anti-alpha-synuclein monoclonal antibody | α-syn PFFAAV α-syn | Phase 2b PASADENA / PADOVA · 2024 | Missed primary |
Cinpanemab (BIIB054) Biogen · Anti-alpha-synuclein monoclonal antibody | α-syn PFF | Phase 2 SPARK · 2021 | Failed |
Inosine NINDS / Parkinson Study Group · Urate elevation / antioxidant | 6-OHDAMPTP mouse | Phase 3 SURE-PD3 · 2021 | Failed |
Nilotinib Georgetown University · c-Abl inhibition promoting alpha-synuclein clearance | AAV α-synα-syn PFF | Phase 2 NILO-PD · 2021 | Failed |
Isradipine NINDS / Parkinson Study Group · Cav1.3 calcium-channel blocker | MPTP mouse6-OHDA | Phase 3 STEADY-PD III · 2020 | Failed |
Creatine NINDS / NET-PD · Mitochondrial bioenergetic buffering | MPTP mouse | Phase 3 NET-PD LS-1 · 2015 | Failed |
Coenzyme Q10 NINDS · Mitochondrial complex-I support / antioxidant | MPTP mouse | Phase 3 QE3 · 2014 | Failed |
CERE-120 (AAV2-neurturin) Ceregene · Neurotrophic factor gene therapy | 6-OHDAMPTP primate | Phase 2b CERE-120 Phase 2b · 2013 | Failed |
GDNF (intraputaminal) Amgen · GDNF/RET neurotrophic signalling | 6-OHDAMPTP primate | Phase 2 Intraputaminal GDNF · 2006 | Failed |
A neurotoxin injected unilaterally into the nigrostriatal tract destroys dopamine neurons on one side, producing a measurable rotational asymmetry that responds to dopaminergic drugs.
A toxin kills dopamine neurons on one side of the brain, so the animal turns in circles. Give it a dopamine drug and the turning stops — which is exactly how levodopa was refined. But nothing here degenerates slowly the way real Parkinson's does.
The predictive-validity problem is being attacked at its root — by defining the disease biologically rather than clinically.
Seed amplification assays detect misfolded alpha-synuclein in cerebrospinal fluid with roughly 88% sensitivity in sporadic PD. For the first time, trials can enrol biologically confirmed patients rather than clinically defined ones — plausibly the reason earlier disease-modifying trials were doomed before they began.
Siderowf et al., Lancet Neurology 2023 (PPMI)
The Neuronal Alpha-Synuclein Disease Integrated Staging System proposes staging from biomarkers instead of motor signs, opening a route to intervening years before the motor threshold — by which point most nigral neurons are already lost.
Simuni et al., Lancet Neurology 2024
LRRK2 and GBA1 programmes derive from human genetics rather than from a toxin model, sidestepping the predictive-validity problem at its root. The trade-off is that the corresponding mice barely degenerate, so efficacy rests on biomarkers until a pivotal trial reads out.
LUMA (BIIB122) programme disclosures