Table 1.
Clinical manifestations, HPβCD treatment data and adverse events
| 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 |
SEQ1–9: patients received intravenous followed by addition of intrathecal treatment, IV1–3: patients received intravenous treatment only
IV intravenous, IT intrathecal, IO Intra-Ommaya, VSGP vertical supranuclear gaze palsy, CVC central venous catheter (Port-a-Cath), N/A not applicable
aLP: lumbar port placed for ease of administration and to eliminate sedation