Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)

The investigators are recruiting children for a research study using a medication known as
IGF-1 (mecasermin or INCRELEX) to see if it improves the health of children with Rett
syndrome (RTT). To participate in the study your child must be female, between the ages of 2
to 12 and have a genetic diagnosis (MECP2 deletion or mutation) of Rett Syndrome. As you may
know, there is no treatment for this illness. Currently, the standard management of Rett
syndrome is supportive, which means attempting to prevent complications and treatment of
symptoms.

This study involves testing an investigational drug, which means that even though IGF-1 is
approved by the Food and Drug Administration (FDA) for use in children, it has not been used
before to treat Rett syndrome specifically. Information from this research will help
determine whether the drug should be approved by the FDA in the future for the treatment of
Rett Syndrome.

There are five major goals to this study:

1. As one of the features of Rett Syndrome is unstable vital signs, the investigators are
trying to determine if IGF-1 has any effect on normalizing your child's pulse, blood
pressure and breathing pattern. During PHASE 2, a device called BioRadio® will be used
to monitor vital signs in a non-invasive way. This information will be recorded and
stored on the accompanying laptop. Before starting PHASE 2, the investigators would
like to "beta-test" the BioRadio® in PHASE 1. As such, the investigators may ask you to
try using the BioRadio® with your child to test the fit and the performance of the
equipment. Should you choose to enroll your child in PHASE 2, the investigators will
then ask that your child wear the BioRadio® for two hours, on two consecutive days
every four weeks.

2. The safety of IGF-1 in children with Rett syndrome. The study personnel will ask you to
complete a medication diary and side effect reporting form on a regular basis. They
will assist you in completing this by telephone interviews. Your child will undergo 2
lumbar punctures performed at the bedside in the clinical research facility. In
addition, laboratory tests will be performed throughout the study to evaluate the
safety of IGF-1. These will be blood tests similar to those provided in routine
clinical care. Your child will undergo regular non-invasive comprehensive physical
examinations including neurological and eye examination, tonsil evaluation,
electrocardiograms (ECG), measurement of height, weight and head circumference.

3. IGF-1 may improve your child's behavior, communication and speech. In order to measure
this, the investigators will evaluate your child once during each month of treatment
with neurodevelopmental assessments and a neurological exam. All of the tests used
during these evaluations are non-invasive. the investigators will also ask you what
your impressions are about her behavior and day-to-day activities through a structured
parental interview and various questionnaires.

4. We will examine your child's cortical function through use of electroencephalography
(EEG) in conjunction with presentation of visual and auditory stimuli. EEG is a
non-invasive way of recording the electrical activity of your child's brain by applying
a net of electrodes to her scalp. Through this we gain insight into how neural function
correlates to the progression of behavioral abnormalities seen in individuals with RTT.
By understanding how this electrical brain activity produces the abnormal behaviors
seen in RTT, we will be better able to identify whether or not treatment with IGF-1
affects the way the brain communicates with the body.

5. Children with Rett Syndrome are often unable to regulate their body temperature and
will sometimes experience "flushing" in their cheeks or have exceptionally cold hands
or feet. The Qsensor® is a non-invasive device worn on a fabric bracelet that
continually measures your child's perspiration level and body temperature. We would
like to use the Qsensor® to determine whether or not IGF-1 improves your child's
ability to regulate her body temperature. As such, we ask that your child wear the
Qsensor® during each study visit. This wrist-worn sensor has been demonstrated to be
safe and comfortable but may cause a slight gray discoloration where the sensor
contacts your child's skin. This discoloration will go away in less than a day. The
Qsensor® is not waterproof, therefore may not be worn in the shower or while your child
is washing her hands. If you believe the device is broken, please contact the study
team immediately.