Spectrum of Peripheral and Autonomic Neuropathies in Patients With aTTRwt Amyloidosis and Response to Patisiran Therapy

Inclusion Criteria:

1. Male or female >18

2. Diagnosis of symptomatic polyneuropathy

3. wtATTR based on cardiac biopsy or Tc99m PYP

4. Negative hATTR sequencing

5. 0 to 0.5 gram/dl serum monoclonal protein.

6. No history of other secondary causes of neuropathy.

7. Have adequate complete blood counts and liver function tests

8. Have negative serology for hepatitis B virus (HBV) and hepatitis C virus (HCV)

Exclusion Criteria:

1. Other Causes of neuropathy as determined by the principle investigator.

2. Has known human immunodeficiency virus (HIV) infection;

3. Primary AL.

4. NYHA Class IV at the Screening visit. 5. Has any of the following laboratoryparameter assessments at screening:

5. Aspartate transaminase (AST) or alanine transaminase (ALT) levels ˃2.0 × theupper limit of normal (ULN).

6. Total bilirubin ˃ULN. Patients with elevated total bilirubin that is secondaryto documented Gilbert's syndrome are eligible if total bilirubin <2 × ULN.

7. International normalized ratio (INR) ˃1.5 (unless patient is on anticoagulanttherapy, in which case excluded if INR ˃3.5).

8. Has eGFR < 30 mL/min/1.73 m2 (using the modification of diet in renaldisease [MDRD] formula). 7. Is currently taking diflunisal; if previously onthis agent, must have at least a 6-month wash-out prior to dosing (Day 1).

9. Is currently taking doxycycline, or tauroursodeoxycholic acid; if previouslyon any of these agents must have completed a 30-day wash-out prior to dosing (Day 1).

10. Received prior TTR-lowering treatment or participated in a gene therapytrial for amyloidosis. 10. Current or future participation in anotherinvestigational device or drug study, Scheduled to occur during this study, orhas received an investigational agent or device within 30 days (or 5 half-livesof the investigational drug, whichever is longer) prior to dosing (Day 1). Inthe case of investigational TTR stabilizer drugs, washout for 6 months prior todosing (Day 1) is required; this does not apply to patients who are ontafamidis at baseline (per inclusion Criterion 4).

11. Requires treatment with calcium channel blockers (eg, verapamil, diltiazem)or digitalis.

12. Other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathydue to valvular heart disease, or cardiomyopathy due to ischemic heart disease.

13. Has non-amyloid disease affecting exercise testing (eg, severe chronicobstructive pulmonary disease, severe arthritis, or peripheral vascular diseaseaffecting ambulation).

14. Had acute coronary syndrome or unstable angina within the past 3 months.

15. Has history of sustained ventricular tachycardia or aborted ventricularfibrillation.

16. Has persistent elevation of systolic (˃180 mmHg) and diastolic (˃100 mmHg)blood pressure that is considered uncontrolled by physician.

17-Has untreated hypo- or hyperthyroidism. 18-Prior or planned heart, liver, or other organ transplant. 19. Had a malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.

20. Has other medical conditions or comorbidities which, in the opinion of the Investigator would interfere with study compliance or data interpretation. 21. Female Is not willing to comply with the contraceptive requirements during the study period.

21. History of illicit drug abuse within the past 5 years that in the opinion of the Investigator would interfere with compliance with study procedures or follow-up visits.