Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Dementia With Lewy Bodies

Inclusion Criteria: 1. Written informed consent 2. Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative (LAR). 3. Clinical diagnosis of DLB according to McKeith et al (7) with both dementia MoCA≥18 and Parkinsonian defined as bradykinesia in combination with rest tremor, rigidity or both UPDRS I-III is less than 50 and/or UPDRS-III between 15 -40 on-state. Dementia and Parkinsonism must be present with at least one other symptom such as fluctuation, visual hallucinations or REM sleep behavioral disorder (RBD) 4. 2.5 ≥Hoehn and Yahr stage ≤3 5. MDS-UPDRS-III 15-40 on-state (or up to 70 on the off state) 6. Abnormal DaTScan 7. Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI 8. Patients between the age of 25-90 years, medically stable 9. Must NOT be stable on mono-amine oxidase (MAO)-B inhibitors (Selegeline or rasagiline) for at least 4 weeks before enrollment and during Nilotinib treatment. 10. Must be medically stable on less than or equal to 800mg Levodopa daily for at least 4 weeks 11. QTc interval 350-460 ms, inclusive 12. Participants must be willing to undergo LP at baseline and 6 months after treatment Exclusion Criteria: 1. Patients with hypokalemia, hypomagnesaemia, or long QT syndrome- QTc≥461 ms 2. Concomitant drugs known to prolong the QTc interval and history of any cardiovascular disease, including myocardial infraction or cardiac failure, angina, arrhythmia 3. History or presence of cardiac conditions including: 1. Cardiovascular or cerebrovascular event (e.g. myocardial infarction, unstable angina, or stroke) 2. Congestive heart failure 3. First, second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances 4. Any history of Torsade de Pointes 4. Treatment with any of the following drugs at the time of screening or the preceding 30 days, and/or planned use over the course of the trial: 1. Treatment with Class IA or III antiarrhythmic drugs (e.g. quinidine) 2. Treatment with QT prolonging drugs (www.crediblemeds.org)- excluding Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g. Citalopram, Paxil, Zoloft, Cymbalta, Sertraline, etc...) 3. Strong CYP3A4 inhibitors (including grapefruit juice). The concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) must be avoided. Grapefruit products may also increase serum concentrations of Nilotinib. Should treatment with any of these agents be required, therapy with Nilotinib should be interrupted. 4. Anticoagulants, including Coumadin (warfarin), heparin, enoxaparin, daltiparin, xarelto, etc. 5. St. John's Wort and the concomitant use of strong other CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) must be avoided since these agents may reduce the concentration of Nilotinib. 5. Abnormal liver function defined as AST and/or ALT \> 100% the upper limit of the normal 6. Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal 7. History of HIV, clinically significant chronic hepatitis, or other active infection 8. Females must not be lactating, pregnant or with possible pregnancy 9. Medical history of liver or pancreatic disease 10. Clinical signs indicating syndromes other than DLB, including, PD, PD with Dementia (PDD), corticobasal degeneration, supranuclear gaze palsy, multiple system atrophy, chronic traumatic encephalopathy, signs of frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement, Babinski sign 11. Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse 12. Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal or other systemic disease or laboratory abnormality 13. Active neoplastic disease, history of cancer five years prior to screening, including breast cancer (history of skin melanoma or stable prostate cancer are not exclusionary) 14. Contraindications to LP: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets \< 100,000, use of Coumadin/warfarin, or history of a bleeding disorder 15. Must not be on any immunosuppressant medications or IVIG 16. Must not be enrolled as an active participant in another clinical study