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Table 1 Clinical manifestations, HPβCD treatment data and adverse events

From: Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis

Patient identification Age at start of IV HPβCD treatment Symptom progression at start of IV treatment Intravenous treatment
Dose/Interval; Length of treatment
Time interval between start of IV and IT HPβCD treatment Intrathecal treatment
Dose/Interval; Length of treatment
Adverse effects, IV HPβCD Adverse effects, IT HPβCD
SEQ1 5 years Ataxia, VSGP, loss of language, dysphagia, global developmental delay 80 mg/kg/day to 2800 mg/kg twice weekly; stable at 2500 mg Q2 weeks; 92 months 18 months 175 mg every 2 weeks; advanced to 350 mg every 2 weeks (IO 50 mg substituted); 74 months None Seizures, increased frequency 24 h post IT
SEQ2 5 years Ataxia, VSGP, loss of language, dysphagia, global developmental delay 80 mg/kg/day to 2800 mg/kg twice weekly; stable at 2500 mg Q2 weeks; 92 months 18 months 175 mg Q2weeks; advanced to 350 mg every 2 weeks (IO 50 mg substituted); 74 months None Seizures, increased frequency 24 h post IT; Intracranial hemorrhage secondary to Ommaya insertion, removal of Ommaya
SEQ3 15 years VSGP, progressive cognitive impairment, seizures, fine motor coordination, psychosis, ataxia 1200 mg/kg with increase over 8 months to 2500 mg/kg weekly; 83 months 16 months 175 mg (advanced to max 875 mg), then stabilized at 350 mg Q15 days; IO 100 to 350 mg every 15 days prior to removal at 10 months; 67 months Port-a-Cath infection (twice), removal after 2nd infection Meningitis, removal of Ommaya
SEQ4 11 years VSGP, progressive cognitive impairment, seizures, fine motor coordination, psychosis, ataxia, gelastic cataplexy 1200 mg/kg with increase over 8 months to 2500 mg/kg weekly; 83 months 16 months IT advanced from 175 to 875 mg Q15 days; now receives IO 100 mg every 15 days; 67 months Port-a-Cath infection (twice), removal after 2nd infection None
SEQ5 13 years Dysarthria, dysphagia, partial complex seizures, worsening ataxia and VSGP, obstructive sleep apnea 500 mg/kg advanced to 2000 mg/kg twice weekly; 72 months 13 months 350 mg Q2 weeks, advanced to 600 mg Q2 weeks, then dropped to 500 mgQ2 weeks; 59 months aLP None Nausea, emesis thought secondary to dehydration; Increased frequency seizures for 24 h post IT; Mild high frequency hearing loss at 500–600 mg
SEQ6 10 years Splenomegaly, mild VSGP; precocious puberty (not related to NPC) 500 mg/kg advanced to 2000 mg/kg twice weekly; 68 months 10 months 350 mg Q2 weeks, advanced to 500 mg Q2 weeks; 59 months None Mild high frequency hearing loss at 500 mg
SEQ7 2 years Progressive neurocognitive decline, VSGP, lung disease, thrombocytopenia, leukopenia 1500 mg/kg weekly to 2000 mg/kg weekly; 58 months 23 months 150 mg every 2 weeks, dose escalation to 750 mg every 2 weeks; 35 months Pneumonia, viral illnesses None reported
SEQ8 21 months Worsened hepatosplenomegaly, severe growth retardation, tracheomalacia/ bronchomalacia (not related to NPC), tracheostomy, ventilator assist 500 mg/kg weekly, escalated by 500 mg/kg monthly to 2000 mg/kg weekly; 30 months 4 months 175 mg every 4 weeks; dose escalated to 400 mg, then decreased to 300 mg every 2 weeks; 26 months CVC malfunction; Seizures Increased seizures frequency for 24 h post IT at higher doses (400 mg)
SEQ9 24 years Progressive neurocognitive decline, memory impairment, falling, gaze palsy, swallowing problems 2500 mg/kg weekly, transitioned to every 2 weeks; 21 months 1 month 350 mg every 2 weeks; 20 months aLP Nausea Nausea
IV1 18 years Spastic quadriplegia, recurrent pneumonia (tracheostomy, ventilator dependent), dysphagia and enterally fed, refractory seizure disorder 500 mg/kg weekly, escalated by 500 mg/kg monthly to 2000 mg/kg weekly; 17 months N/A N/A Port-a-Cath infection; proteinuria, elevated transaminases 5x baseline; fevers, hypertension N/A
IV2 27 years Hepatosplenomegaly, mild thrombocytopenia, severe neurocognitive impairment, wheelchair dependent, VSGP, nasogastric tube fed, severe dysmetria, seizures 1700 mg/kg weekly; unknown total length of treatment; report of 26 months for safety data N/A N/A Pneumonia, sinus infection, rash with infusion N/A
IV3 25 years Schizophrenia type behavior, gaze palsy, dysarthria, dysphagia, hepatosplenomegaly, thrombocytopenia 2600 mg/kg weekly; unknown total length of treatment; report of 32 months for safety data N/A N/A Tremors, chills, emesis, fever or headache during infusion (3 occasions) N/A
  1. SEQ1–9: patients received intravenous followed by addition of intrathecal treatment, IV1–3: patients received intravenous treatment only
  2. IV intravenous, IT intrathecal, IO Intra-Ommaya, VSGP vertical supranuclear gaze palsy, CVC central venous catheter (Port-a-Cath), N/A not applicable
  3. aLP: lumbar port placed for ease of administration and to eliminate sedation