Nilotinib: Georgetown and NILO-PD

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

• Georgetown trial: Fernando Pagan, Michaeline Hebron and colleagues, Georgetown University; single centre; NCT02954978. JAMA Neurology 2020;77:309–317.
• NILO-PD: Tanya Simuni (Northwestern University) and the Parkinson Study Group; 25 US sites; NCT03205488; collaborators Rochester, Iowa and the Michael J. Fox Foundation. JAMA Neurology 2021;78:312–320.

What happened

Nilotinib blocks c-Abl, an enzyme linked to the loss of parkin's protective function (landmark 211). A tiny uncontrolled pilot and a public dispute came first (landmark 68).

Georgetown (75 patients, moderately severe Parkinson's). Randomised 1:1:1 to placebo, 150 mg or 300 mg a day for 12 months, then a 3-month washout. Recruitment ran May 2017 to April 2018.

• Main aim: safety and drug levels. More serious adverse events occurred on nilotinib: 6 of 25 (24%) at 150 mg and 12 of 25 (48%) at 300 mg, against 4 of 25 (16%) on placebo.
• Exploratory spinal-fluid markers moved: dopamine breakdown products (HVA, DOPAC) rose, alpha-synuclein oligomers fell at 150 mg only, and phosphorylated tau fell at both doses.
• On the strength of the marker changes the authors called for a Phase 3. The trial was not designed to show a clinical benefit.

NILO-PD (76 patients, mean disease duration 9.9 years). Randomised 1:1:1 to placebo, 150 mg or 300 mg a day for 6 months, with a 2-month washout. The main measures were safety and tolerability.

• Tolerability was acceptable (84%, 76% and 77% completed on assigned dose).
• Spinal-fluid nilotinib was 0.2 to 0.3% of the blood level.
• Motor scores in the "on" state were worse on both doses (significant at month 1 for 300 mg); off-state change did not differ (P = 0.17).
• No change in spinal-fluid dopamine breakdown products, so the Georgetown marker shift was not reproduced.
• The authors concluded nilotinib should not be tested further in Parkinson's.

Why it moved us toward a cure

These were the first controlled tests of blocking c-Abl in people. The negative independent trial showed the drug's brain exposure was too low to test the idea fairly, which set the bar for later c-Abl drugs designed to enter the brain (landmark 323, 174, 219).

Outcome

Dead end for nilotinib. The c-Abl idea itself remains open because other drugs reach the brain better.

Sources

• Pagan et al., JAMA Neurol 2020;77:309–317, DOI 10.1001/jamaneurol.2019.4200 (abstract via Europe PMC) · NCT02954978 (results posted; read 19 Oct 2026)
• Simuni et al., JAMA Neurol 2021;78:312–320, DOI 10.1001/jamaneurol.2020.4725 (abstract via Europe PMC) · NCT03205488
• Not yet verified: the Georgetown trial's funder and its clinical (MDS-UPDRS) results, which I did not read; why the pilot's design is called randomised by some sources; the full texts.