Cellcept for Treatment of Juvenile Neuronal Ceroid Lipofuscinosis

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a fatal disorder. Currently treatment is
symptomatic. Thus, there is a real need to intervene and slow the progression of this
disease. Preliminary data on genetic knock-down of the ability to mount an immune response
in cln3-knockout mice is supportive of a strategy for treating JNCL with an
immuno-suppressive agent. Many drugs with the ability to suppress the immune system are
steroidal and deemed unsuitable for long-term administration to children. Mycophenolate
mofetil (CellCept) is used as an immunosuppressive agent in allogenic transplants in
pediatric patients and is therefore approved by the Food and Drug Administration (FDA) for
pediatric use.

The study design is a double-blind, randomized, 22-week cross-over study of mycophenolate
mofetil vs. placebo. After a 4-week washout period, subjects will undergo blinded crossover
from active study drug to placebo or from placebo to active study drug.

Subjects and caregivers will be evaluated in person in the University of Rochester Batten
Center (URBC) at screening/baseline, and at weeks 8, 12, and 20. In addition, subjects will
be evaluated by their local clinician who is a formalized member of the research team. Such
contacts will occur at Weeks 2, 4, 14, 16, and any unscheduled or early termination visits.
There will also be regular telephone contact between the URBC and the local clinician.

We have selected the dosage currently FDA approved for use in children being treated for
prophylaxis of renal transplant rejection.

Inclusion Criteria:

- JNCL as determined by a characteristic clinical presentation and confirmatory genetic
evidence.

- Able to walk 10 feet without assistance beyond that required due to vision
impairment.

- Subjects with local treating clinician (pediatrician or neurologist) willing to
conduct the trial according to the protocol, good clinical practice, and applicable
regulations.

- Subjects with a parent/legal guardian willing to accompany them to all study visits,
oversee study drug compliance, and monitor and report to local treating
clinician/investigator and the URBC investigative personnel any signs of adversity.

Exclusion Criteria:

- Inability to tolerate oral administration of medications

- Concomitant medical condition, which, in the opinion of the local treating clinician,
the parent(s)/guardian, or the URBC study investigator would place the child at
greater than acceptable risk from: 1) travel by plane or car to the URBC on four
occasions over the course of 22 weeks, 2) exposure to mycophenolate mofetil at
protocol defined dosages for periods up to 8 weeks.

- Anticipated inability of the child (on the part of the investigator, parent/guardian,
or URBC study personnel) to comply with the rigors of the protocol..

- Use of disallowed concomitant medications.

- Administration of immunosuppressive medications

- History of any prior exposure to mycophenolate mofetil

- History of hypersensitivity to mycophenolate mofetil, or any other component of the
product

- History of frank gastrointestinal hemorrhage, ulceration, or melena

- White blood cell count < 3000/μL, absolute neutrophil count (ANC) < 1500/μL,
hemoglobin < 10g/dL, or thrombocytopenia <100,000/μL.

- Abnormal liver function (aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) or bilirubin greater than 3 times the upper limit of normal)

- Pregnancy or vulnerability to engage in sexual intercourse based on report of the
parent/guardian, judgment of the local treating clinician/investigator or judgment of
the URBC study personnel.

- Positive Tuberculosis test

- Immunizations not up to date for age according to Centers for Disease Control
guidelines