The primary objective of the study is to obtain preliminary safety and tolerability data with davunetide (NAP, AL-108) in patients with a tauopathy (frontotemporal lobar degeneration [FTLD] with predicted tau pathology, corticobasal degeneration syndrome [CBS] or progressive supranuclear palsy [PSP]). The secondary objectives of this study are to obtain preliminary data on short term changes (at 12 weeks) in a variety of clinical, functional and biomarker measurements from baseline, including cerebrospinal fluid (CSF) tau levels, eye movements, and brain MRI measurements.

Inclusion Criteria:

1. A probable tauopathy defined as:

   • Probable or possible progressive supranuclear palsy (PSP) defined as:

     1. at least a 12-month history of:

        • postural instability or falls during the first 3 years that symptoms are present and
        • prominent decreased saccade velocity or supranuclear ophthalmoplegia;

     2. age at symptom onset ≥ 40 years by history; and

     3. an akinetic-rigid syndrome with prominent axial rigidity.

   OR,

   • Progressive nonfluent aphasia (PNFA)defined as:

     1. at least a 6-month history of difficulty with expressive speech characterized by at least 3 of the following:

        • apraxia of speech,
        • speech hesitancy,
        • labored speech,
        • word finding difficulty, or
        • agrammatism; and

     2. the symptoms above are the subject's principal neurological deficit and the symptoms constituted the initial clinical presentation.

   OR,

   • Corticobasal Degeneration syndrome (CBS) defined as:

     1. at least a 6-month history of progressive cortical dysfunction evidenced by at least one of the following:

        • ideomotor apraxia,
        • alien limb phenomenon,
        • cortical sensory loss,
        • focal or asymmetric myoclonus, or
        • apraxia of speech /nonfluent aphasia; and

     2. at least a 6-month history of progressive extrapyramidal dysfunction evidenced by at least one of the following:

        • focal or asymmetrical rigidity (limb or axial) or asymmetrical dystonia (limb or axial); and
        • lacking prominent and sustained L-dopa response.

   OR

   • Frontotemporal Dementia with Parkinsonism linked to Chromosome 17 (FTDP-17): Motor, cognitive or behavioral dysfunction, as defined below associated with a previously demonstrated mutation of the MAPT gene, and meets criteria for PNFA, CBS or PSP as defined above, or CDR-FTLD ≥ 1.0.

2. Documented age 40-85 years at the time of the onset of symptoms associated with the neurological deficits described in inclusion criterion 1.

3. Judged by investigator to be able to comply with neuropsychological evaluation at baseline.

4. Must have reliable caregiver accompany subject to all study visits. Caregiver must read, understand and speak local language fluently in order to ensure comprehension of informed consent form and informant-based assessments of subject. Caregiver must also have frequent contact with subject (at least 3 times per week for one hour) and be willing to monitor study medication compliance and the subject's health and concomitant medications throughout the study.

5. FTLD Modified Hachinski score ≤ 3.(Knopman et al., 2008) This modified Hachinski will not include the focal neurological signs, symptoms or pseudobulbar affect questions, given the prominence of all three in CBS/PSP.

6. MMSE ≥ 15 at Visit 1.

7. Written informed consent provided by both subject and caregiver who are both fluent English speakers.

8. Subject resides outside a skilled nursing facility or dementia care facility. Residence in an assisted living facility is allowed.

9. If the subject is receiving levodopa/carbidopa, a dopamine agonist, COMT inhibitor or other Parkinson's medication the dose must have been stable for at least 120 days prior to Visit 1 and must remain stable for the duration of the study.

10. Able to tolerate MRI scan during screening without use of sedation.

11. Able to ambulate with or without assistance.

Exclusion Criteria:

1. Insufficient fluency in local language to complete neuropsychological and functional assessments.

2. A diagnosis of Amyotrophic Lateral Sclerosis or other motor neuron disease.

3. Any of the following:

   • Abrupt onset of symptoms defined in inclusion criteria 1 associated with ictal events,
   • Head trauma related to onset of symptoms defined in inclusion criteria 1,
   • Severe amnesia within 6 months of the symptoms defined in inclusion criteria 1,
   • Cerebellar ataxia,
   • Choreoathetosis,
   • Early, symptomatic autonomic dysfunction, or
   • Tremor at rest.

4. History of other significant neurological or psychiatric disorders including, but not limited to, Alzheimer's disease, dementia with Lewy bodies, Prion disease, stroke, Parkinson's disease, any psychotic disorder, severe bipolar or unipolar depression, seizure disorder, tumor or other space-occupying lesion, or head injury with loss of consciousness within past 20 years temporally related to onset of symptoms.

5. Within 4 weeks of screening or during the course of the study, concurrent treatment with memantine (stable dose memantine, greater than 6 months is allowed), acetylcholinesterase inhibitors, antipsychotic agents or mood stabilizers (valproate, lithium, etc.) or benzodiazepines (other than temazepam or zolpidem).

6. Treatment with lithium, methylene blue, tramiprosate, ketone bodies, Dimebon or any putative disease-modifying agent directed at tau within 90 days of screening.

7. A history of alcohol or substance abuse within 1 year prior to screening and deemed to be clinically significant by the site investigator.

8. Any malignancy (other than non-metastatic basal cell carcinoma of the skin) within 5 years of Visit 1 or current clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease. For the non-cancer conditions, if the condition has been stable for at least the past year and is judged by the site investigator not to interfere with the patient's participation in the study, the patient may be included.

9. Clinically significant lab abnormalities at screening, including creatinine ≥ 2.5 mg/dL, vitamin B12 below laboratory normal reference range, or TSH above laboratory normal reference range.

10. Systolic blood pressure greater than 180 or less than 90 mm Hg. Diastolic blood pressure greater than 105 or less than 50 mm Hg.

11. ECG abnormal at screening and judged to be clinically significant by the site investigator.

12. Treatment with any investigational drugs or device or participation in an investigational drug study within 60 days of screening.

13. Known history of serum or plasma progranulin level < 110.9 ng/mL.

14. Known presence of known disease-associated mutation in TDP-43, PGRN, CHMPB2 or VCP genes or any other FTLD causative genes not associated with underlying tau pathology (eg. Chr. 9 associated FTD).

15. History of deep brain stimulator surgery other than sham surgery for DBS clinical trial.

16. History of early, prominent REM behavior disorder.

17. Women of childbearing potential who are not using at least two forms of medically recognized contraception.

18. An employee or relative of an employee of Allon Therapeutics

19. Significant anatomical nasal abnormality (e.g., septal deviation obstructing airflow to at least one nostril or septal perforation) or history of nasal turbinate surgery.

20. History of a clinically significant medical condition that that would interfere with the subject's ability to comply with study instructions, would place the subject at increased risk, or might confound the interpretation of the study results.

21. Contraindication to MRI examination for any reason (eg., severe claustrophobia, ferromagnetic metal in body, etc.).

22. Structural abnormality on MRI within 2 years of baseline that precludes diagnosis of PSP, CBS or PNFA, such as cortical infarct in brain region that might account for subject's symptoms.

23. In subjects receiving anti-Parkinson's Disease medication at the time of screening, in the opinion of the investigator substantial worsening of motor signs or symptoms compared to normal functioning following overnight withdrawal of the anti-Parkinson medication.

24. Subject not willing to attempt LP.