Convection-Enhanced Delivery of Glucocerebrosidase to Treat Type 2 Gaucher Disease
Convection-Enhanced Delivery of Glucocerebrosidase to Treat Type 2 Gaucher Disease
This study will use an experimental method of delivering the enzyme glucocerebrosidase
 directly into the brain of a patient with Gaucher disease to treat disease symptoms. Patients
 with Gaucher disease have insufficient levels of glucocerebrosidase. As a result, substances
 normally broken down by this enzyme accumulate in the body, causing damage to the brain and
 other organs. Symptoms of Gaucher disease outside the brain can be treated by infusing the
 missing enzyme intravenously (IV, through a vein). However, IV infusions do not help the
 neurologic symptoms of the disease, because the enzyme cannot get into the brain. This study
 will use a new technique called convection-enhanced delivery to try to introduce
 glucocerebrosidase directly into the brain.

 This single-patient study includes an 8-month-old male with Type 2 Gaucher disease with
 progressive neurological decline.

 In preparation for the enzyme infusion, the patient will have a complete physical
 examination, including a detailed neurological examination, and blood and urine tests. On the
 day of surgery, the child will be placed under general anesthesia for magnetic resonance
 imaging (MRI) of the brain. MRI uses a magnetic field and radio waves to produce images of
 body tissues and organs. For this procedure, the child lies on a table that is moved into the
 scanner (a narrow cylinder), wearing earplugs to protect his hearing from the loud knocking
 and thumping sounds that occur during the scanning process. He will then be brought to the
 operating room for the infusion procedure, as follows:

 An incision will be made in the scalp and a small hole drilled through the skull. Then, a
 small tube (cannula) will be positioned through the hole into the target area in the brain.
 Once the tip of the cannula is in place, it will be connected with tubing to a syringe filled
 with glucocerebrosidase in saline (salt water). The child will then have a second MRI scan to
 make sure the cannula is placed correctly and to monitor delivery of the glucocerebrosidase
 to the brain. The child will be monitored closely with MRI scans every 30 to 60 minutes
 during the infusion to look for fluid in the brain and determine the extent of the enzyme
 perfusion. The infusion will last no longer than 6 hours and will be stopped when the full
 dose of enzyme has been delivered. The cannula will be removed and the scalp incision closed.
 The child will stay in the hospital for observation from 4 to 10 days, with at least 24 hours
 in the intensive care unit and 3 to 7 days in the pediatric unit.

 The child will be seen in the clinic two weeks after discharge and then once a month for 3
 months to evaluate any possible effects of the surgery. These follow-up visits include a
 repeat MRI scan and neurological examination. After the first 3 months, visits may be less
 frequent.

 If the child continues to have symptoms during the course of follow-up or his neurologic
 status worsens, additional enzyme infusions will be offered, possibly including treatment of
 the brainstem. If the child gains no benefit after three infusions have been performed, no
 additional infusions will be offered. If there appears to be any neurological benefit,
 additional infusions may be offered.
Objective. To overcome the previous delivery limitations and to provide enzyme to the
 deficient sites in the central nervous system (CNS) of a Type 2 Gaucher disease patient, we
 will investigate the use of convection-enhanced delivery (CED) to perfuse specific sites
 within the CNS with glucocerebrosidase in an effort to ameliorate that patient's neurologic
 symptomatology and prolong his life.

 Study population. This is a single patient study that includes a male infant (8 months of
 age) with Type 2 Gaucher disease that has been diagnosed by clinical, laboratory and genetic
 testing. The natural history of acute neuronopathic (Type 2) Gaucher disease is progressive
 neurological decline that is rapidly fatal.

 Design. We propose using CED of glucocerebrosidase to the CNS to treat the neurologic signs
 and symptoms in this Type 2 Gaucher patient. Regions of infusion within the CNS will be
 targeted based on neurologic findings.

 Outcome measures. Detailed clinical and neurologic examinations will be performed pre- (3
 days before infusion) and post-infusion (1, 14, 30, and 90 days after infusion then every 3
 months until study completion) to determine stabilization or improvement in neurologic signs
 and symptoms. Survival will also be used to determine the efficacy of this treatment.
-  INCLUSION CRITERIA

 The patient is eligible because he has Type 2 Gaucher disease.

 EXCLUSION CRITERIA

 The patient may not be eligible to receive CED of glucocerebrosidase if he:

 1. Is not healthy enough to undergo surgery or general anesthesia.

 2. Has an uncorrectable bleeding disorder.

 3. Is not able to undergo magnetic resonance (MR)-imaging.