Section 12
Rare & Genetic Neurology
Amyloid Neuropathy, Ataxia & Neurodevelopmental
17 AGENTS
Vutrisiran
AmvuttrasiRNA (TTR-directed)
- Forms
- SC: 25mg/0.5mL prefilled syringe
- Dose
- 25mg SC every 3 months (given by healthcare professional); vitamin A supplementation advised
- MOA
- Silences hepatic transthyretin (TTR) synthesis
Patisiran
OnpattrosiRNA (TTR-directed) · IV
- Forms
- IV: 10mg/5mL (2mg/mL) vial
- Dose
- Under 100kg: 0.3mg/kg IV every 3 weeks | 100kg or more: 30mg every 3 weeks; premedicate
- MOA
- Silences hepatic transthyretin (TTR) synthesis
Eplontersen
WainuaAntisense oligonucleotide (TTR)
- Forms
- SC autoinjector or prefilled syringe: 45mg/0.8mL
- Dose
- 45mg SC once monthly
- MOA
- Degrades TTR mRNA, ↓hepatic TTR production
Omaveloxolone
SkyclarysNrf2 activator
- Forms
- Cap: 50mg
- Dose
- 150mg (3 caps) once daily on empty stomach; reduce in hepatic impairment (Friedreich's ataxia, age 16+)
- MOA
- Activates Nrf2 pathway (exact mechanism unknown)
Trofinetide
DaybueSynthetic GPE analog
- Forms
- Sol: 200mg/mL
- Dose
- Weight-based BID: 5,000mg (9 to <12kg) up to 12,000mg (50kg+), Rett syndrome age 2+
- MOA
- IGF-1-related; ↑synaptic function (Rett syndrome)
Arimoclomol
MiplyffaNPC therapy
- Forms
- Cap: 47, 62, 93, 124mg
- Dose
- Niemann-Pick type C (with miglustat), age 2+: weight-based, three times daily — 8-15kg 47mg; over 15-30kg 62mg; over 30-55kg 93mg; over 55kg 124mg
- MOA
- Mechanism of action not established
Levacetylleucine
AqneursaModified amino acid · NPC therapy
- Forms
- Granules for oral suspension: 1g unit-dose packets
- Dose
- Niemann-Pick type C, weight over 15kg: 15-<25kg 2g/day; 25-<35kg 3g/day; 35kg or more 4g/day, split morning/afternoon/evening per label
- MOA
- Mechanism not established (N-acetyl-L-leucine)
Miglustat
Zavesca / YargesaGlucosylceramide synthase inhibitor
- Forms
- Cap: 100mg
- Dose
- Niemann-Pick type C (off-label in US): adults 200mg three times daily; pediatric dosing by body surface area | Gaucher type 1: 100mg three times daily
- MOA
- Substrate reduction of glycosphingolipid synthesis
Cerliponase alfa
BrineuraEnzyme replacement (TPP1) · intraventricular
- Forms
- Intraventricular: 150mg/5mL vials with Intraventricular Electrolytes
- Dose
- CLN2: 300mg ICV every other week (age 2+) over about 4.5h; under 2 years lower doses (100mg birth to under 6 months; 150mg 6 months to under 1 year; 200mg x4 then 300mg for 1 to under 2 years)
- MOA
- Replaces tripeptidyl peptidase 1 (TPP1)
Selumetinib
KoselugoMEK1/2 inhibitor
- Forms
- Cap: 10, 25mg | Granules (capsule for opening)
- Dose
- NF1 plexiform neurofibromas: 25mg/m² twice daily by body surface area (pediatric 2+; check current label for adult use)
- MOA
- Inhibits MEK1/2 in the RAS-MAPK pathway
Mirdametinib
GomekliMEK1/2 inhibitor
- Forms
- Cap: 1, 2mg | Tab for oral suspension: 1mg
- Dose
- NF1 plexiform neurofibromas, age 2+: BID on days 1-21 of 28-day cycle by BSA — 0.4-0.69m² 1mg; 0.7-1.04 2mg; 1.05-1.49 3mg; 1.5+ 4mg (max 4mg/dose)
- MOA
- Inhibits MEK1/2 in the RAS-MAPK pathway
Eladocagene exuparvovec
KebilidiAAV gene therapy
- Forms
- Intraputaminal infusion suspension (AAV2-hAADC gene therapy)
- Dose
- AADC deficiency: one-time stereotactic neurosurgical infusion into the putamen at a specialized center
- MOA
- Delivers a functional DDC (AADC) gene to putaminal neurons
Atidarsagene autotemcel
LenmeldyAutologous stem-cell gene therapy
- Forms
- IV suspension: autologous CD34+ gene-modified cells
- Dose
- Metachromatic leukodystrophy (pre-symptomatic late infantile or early juvenile; early symptomatic early juvenile): single IV infusion after myeloablative busulfan conditioning
- MOA
- Lentiviral ARSA gene transfer into CD34+ cells
Elivaldogene autotemcel
SkysonaAutologous stem-cell gene therapy
- Forms
- IV suspension: autologous CD34+ gene-modified cells
- Dose
- Early active cerebral adrenoleukodystrophy, boys 4-17 (indication restricted in Aug 2025 to those without an available HLA-matched donor): single IV infusion after busulfan conditioning
- MOA
- Lentiviral ABCD1 gene transfer into CD34+ cells
Agalsidase beta
FabrazymeEnzyme replacement (α-Gal A)
- Forms
- IV: 5, 35mg vials
- Dose
- Fabry disease, age 2+: 1mg/kg IV every 2 weeks
- MOA
- Replaces alpha-galactosidase A to clear Gb3
Pegunigalsidase alfa
ElfabrioEnzyme replacement (α-Gal A, PEGylated)
- Forms
- IV: 20mg/10mL vial
- Dose
- Fabry disease, adults: 1mg/kg IV every 2 weeks
- MOA
- PEGylated alpha-galactosidase A with a longer half-life
Migalastat
GalafoldPharmacological chaperone
- Forms
- Cap: 123mg
- Dose
- Fabry disease with an amenable GLA variant, adults: 123mg once every other day on an empty stomach (no food 2h before or after)
- MOA
- Stabilizes amenable mutant alpha-Gal A for lysosomal trafficking