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 previouslyon this agent, must have at least a 6-month wash-out prior to dosing (Day 1).

9. Is currently taking doxycycline, or tauroursodeoxycholic acid; ifpreviously on any of these agents must have completed a 30-day wash-outprior 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 thisstudy, or has received an investigational agent or device within 30 days (or 5 half-lives of the investigational drug, whichever is longer) priorto dosing (Day 1). In the case of investigational TTR stabilizer drugs,washout for 6 months prior to dosing (Day 1) is required; this does notapply to patients who are on tafamidis at baseline (per inclusionCriterion 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 heartdisease.

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

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

15. Has history of sustained ventricular tachycardia or abortedventricular fibrillation.

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 theInvestigator would interfere with study compliance or data interpretation. 21.Female Is not willing to comply with the contraceptive requirements during the studyperiod.

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