Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease

• INCLUSION CRITERIA:

  1. Aged greater than or equal to 7 and less than or equal to 25 years old at time of enrollment, either gender and any ethnicity.

  2. Diagnosis of NPC1 based upon one of the following:

     1. Two NPC1 mutations;
     2. Positive filipin staining and at least one NPC1 mutation;
     3. Vertical supranuclear gaze palsy (VSNGP) in combination with either:

     i. One NPC1 mutation, or

     ii. Positive filipin staining and no NPC2 mutations.

  3. Patients with at least one neurological manifestation of NPC1. For example, but not limited to, hearing loss, vertical supranuclear gaze palsy, ataxia, dementia, dystonia, seizures, dysarthria, or dysphagia.
  4. Ability to travel to the NIH CC repeatedly for evaluation and follow-up.
  5. If taking miglustat, the patient must have been taking a constant dose of the medication for no less than 3 months prior to baseline evaluation and must be willing to maintain that dose level for the duration of the trial.
  6. Willing to discontinue all non-prescription supplements, with the exception of an age-appropriate multivitamin.
  7. Women of reproductive age must be willing to use an effective method of contraception for the duration of the trial.
  8. Willing to undergo placement of an Ommaya reservoir for administration of an experimental drug.
  9. Willing to participate in all aspects of trial design including serial blood and CSF collections.

EXCLUSION CRITERIA:

1. Aged below 7 or above 25 years of age at enrollment in the trial.
2. Weight less than 10 kg.
3. Severe manifestations of NPC1 that would interfere with the patient's ability to comply with the requirements of this protocol.
4. Neurologically asymptomatic patients.
5. Patients who have received any form of cyclodextrin in an attempt to treat NPC1. Treatment with another drug preparation for another medical indication that contains cyclodextrin as an excipient, will not exclude a patient.
6. History of hypersensitivity reactions to cyclodextrin or components of the formulation.
7. Pregnancy or breastfeeding at any time during the study.
8. Patients with suspected infection of the CNS or any systemic infection.
9. Neutropenia, defined as an absolute neutrophil count (ANC) of less than 1,500.
10. Thrombocytopenia (a platelet count of less than 75,000 per cubic millimeter).
11. Evidence of disturbed circulation of CSF.
12. Contraindication to placement of an Ommaya reservoir or anesthesia.
13. Prior use of anticoagulants or history/presence of a bleeding disorder.
14. Hepatic laboratory parameters (aspartate aminotransferase [AST], alanine aminotransferase [ALT],) greater than 4-times upper limit of normal.
15. Presence of anemia defined as two standard deviations below normal for age and gender.
16. Serum creatinine level greater than 1.5 times the upper limit of normal.
17. Hematuria on a single urinalysis, as defined by the American Urological Association (AUA) as five or more red blood cells per high-power field on microscopic evaluation of urinary sediment from a properly collected urinalysis specimen. The patient will not be excluded if 2 subsequent urine specimens are negative for hematuria as defined by the AUA.
18. Proteinuria (1+ protein on urinalysis) unless evaluated and classified as benign by patient's primary medical provider.
19. Active pulmonary disease, oxygen requirement or clinically significant history of decreased blood oxygen saturation, pulmonary therapy, or requiring active suction.
20. Patients unable to complete a behavioral audiologic evaluation including pure-tone threshold assessment (500 Hz to 8000 Hz) to monitor for ototoxicity.
21. Patients with uncontrolled seizures, specifically: greater than 1 seizure over a 2-month period (quantified over the 6 months prior to enrollment), patients requiring antiepileptic medication changes (other than dose adjustment for weight) in the 6 months prior to enrollment), or requiring 2 or more antiepileptic medications to control seizures.
22. Patients, who in the opinion of the investigators are unable to comply with the protocol or have specific health concerns that would potentially increase the risk of participation.