Pilot Study of alpha1-antitrypsin to Treat Neuromyelitis Optica Relapses

A Single Center Open Label Pilot Study of Alpha1-Antitrypsin: A Novel Treatment to Mitigate Neuromyelitis Optica Attacks

Neuromyelitis Optica (NMO) is a rare, devastating demyelinating disease of the central nervous system (CNS) that has different causes and treatments from the more common demyelinating disease multiple sclerosis (MS). Current NMO therapies are nonspecific and have varying and often suboptimal benefit. The investigators will evaluate whether use of alpha1-antitrypsin (A1AT, an FDA-approved medication for patients with congenital deficiency of A1AT associated with emphysema) can benefit acute attacks of NMO, improving patient disability and quality of life.

Inclusion Criteria:

• Provide written informed consent.
• Age ≥18 and ≤ 75 years.
• Diagnosis of NMO or NMO spectrum disorder (NMOSD). The diagnosis of NMO will conform to the 2006 Wingerchuk criteria.1, 2 The diagnosis of NMOSD will include patients with relapsing optic neuritis and aquaporin-4 antibody (AQP4) seropositivity or patients with relapsing longitudinally extensive transverse myelitis and AQP4 seropositivity.2-5 NMO and NMOSD will be collectively referred to as NMO.
• AQP4-antibody positivity.
• Present with an acute NMO attack (see definition below).
• Patients must not have a history of clinically significant infusion reactions with administration of biologic agents.
• If on chronic treatment for NMO, treatment was initiated at least 3 months earlier and medication dose is stable. Additional restrictions will be placed on changes in concomitant symptomatic medications.
• A female subject of childbearing potential must have a negative serum pregnancy test at the screening visit and agree to use a medically reliable method of contraception (e.g., barrier with either spermicide or hormonal contraception) until study completion.
• Agree to answer the questions on the Columbia Suicide Severity Rating Scale at each specified visit.

Exclusion Criteria:

• A woman who is pregnant, breastfeeding, or planning pregnancy.
• If the patient is enrolled in any other experimental trial or on other experimental therapy.
• If the patient has a known IgA deficiency with IgA-antibodies.
• Any medical condition or clinically significant laboratory abnormality that in the Investigator's judgment may affect the patient's ability to safely complete the study.

Acute attack:

• The occurrence of new or worsening neurological symptoms consistent with optic neuritis, transverse myelitis, or a brain lesion that develop acutely (i.e., patients must present within 7 days of symptom onset).
• The symptoms must persist for at least 48 hours, are not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to concomitant medications).
• The symptoms must be accompanied by sensory, motor or visual acuity objective deficits, which must be verified by the examining physician.
• A single episode of a paroxysmal symptom (e.g., tonic spasm) is not a relapse; however, the new onset of multiple occurrences of a paroxysmal symptom over at least 48 hours can be a relapse if accompanied by a new, corresponding objective deficit.
• Sensory symptoms with no change on clinical examination, fatigue, mood change, or bladder or bowel urgency or incontinence will not be sufficient to establish a relapse.