A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy

1. Meets National Institute of Neurological Disorders and Stroke - Society for Progressive Supranuclear Palsy (NINDS-SPSP) probable or possible PSP criteria,(Litvan 1996a) as modified from the AL-108-231 trial.(Boxer 2014)

2. Aged 50-85

3. Agrees to 3 magnetic resonance imaging (MRI) or subject to investigator's discretion

4. MRI at screening is consistent with PSP (≤4 microhemorrhages and no large strokes or severe white matter disease)

5. Mini-Mental State Examination (MMSE) score 14-30

6. Stable medications for 2 months prior to screening, including FDA approved Alzheimer's disease (AD) medications and Parkinson's disease medications

7. Availability of a study partner who knows the patient well and is willing to accompany the patient to all trial visits and to participate in questionnaires

8. Agrees to 2 lumbar punctures for cerebrospinal fluid (CSF) examination

9. Signed and dated written informed consent obtained from the subject and subject's caregiver in accordance with local IRB regulations

10. Males and all WCBP agree to abstain from sex or use an adequate method of contraception for the duration of the study and for 30 days after the last dose of study drug.

1. Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD (McKhann et al. 2011);

2. Any medical condition other than PSP that could account for cognitive deficits (e.g., active seizure disorder, stroke, vascular dementia);

3. A prominent and sustained response to levodopa therapy;

4. History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);

5. History of hypertension (repeated elevations in blood pressure exceeding 180 mm Hg systolic or 100 mm Hg diastolic; medical intervention indicated);

6. History of severe gastrointestinal bleed, or gastric or peptic ulcers;

7. History of aspirin triad (i.e., aspirin allergy, nasal polyps and asthma) or asthma;

8. History of major psychiatric illness or untreated depression;

9. Neutrophil count <1,500/mm3, platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin >1.5 x ULN, alanine aminotransferase (ALT) >3 x ULN, aspartate aminotransferase (AST) >3 x ULN, or INR >1.2 at Screening evaluations;

10. Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of study data;

11. Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection;

12. Current clinically significant viral infection. Subjects with chicken pox, influenza, or flu symptoms are not eligible;

13. Major surgery within four weeks prior to Screening;

14. Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening;

15. Treatment with another investigational drug or participation in another interventional clinical trial within 3 months of Screening;

16. Chronic use of other NSAIDs or salicylates for any reason, except for daily baby aspirin (81 mg);

17. Concurrent treatment with thiazides or loop diuretics;

18. Concurrent use of oral corticosteroids or angiotensin-converting enzyme (ACE) inhibitors;

19. Treatment with any human blood product, including intravenous immunoglobulin, during the 6 months prior to Screening or during the trial;

20. Known hypersensitivity to the inactive ingredients in the study drug;

21. Pregnant or lactating;

22. Positive pregnancy test at Screening or Baseline (Day 1);

23. Cancer within 5 years of Screening, except for non-metastatic skin cancer or nonmetastatic prostate cancer not expected to cause significant morbidity or mortality within one year of Baseline.