Treatment of Rett Syndrome With Recombinant Human IGF-1

Enrolled subjects will complete five study periods: screening, two 20-week long treatment
periods, a 28-week break between treatment periods ("washout"), and a follow-up phone call 4
weeks after all treatment ends. Subjects will be chosen at random to receive either IGF-1 or
placebo during the first treatment period and then switch to the alternate medication for the
second treatment period. Therefore, by completion of the trial, all subjects will have
received treatment with IGF-1 for 20 weeks. The study will be double-blinded; meaning,
neither subjects' families nor study investigators will know who is receiving IGF-1 or
placebo at any time. Treatment must be administered by the caregiver twice daily through
subcutaneous (just underneath the skin) injections. Caregivers will be trained by research
nurses in how to administer the medication. Participation in this study will last
approximately eighteen months.

Throughout the course of the trial, investigators will collect information to assess the
effects of IGF-1 and monitor for safety. Families must attend study visits at Boston
Children's Hospital a total of seven times (including the screening visit) over the course of
18 months. These visits cannot be completed at any other hospital. Parents will fill out
questionnaires and undergo a structured interview reporting on their child's health,
behavior, and mood. Subjects will undergo clinical and physical examinations by a study
doctor. Non-invasive devices and cameras will also be used to monitor things like breathing,
hand movements, heart rate, and body temperature. Blood and urine will be collected for
routine laboratory tests to monitor for safety. Investigators will also monitor safety by
asking parents to complete a medication diary and side effect reporting form on a regular
basis. Between trips to Boston Children's Hospital, parents will complete a set of online
questionnaires and undergo a structured interview over the phone.

The cost of travel and lodging during research-related visits to and from the hospital will
not be covered by the study. If a condition or illness is identified during the trial (and is
determined to be unrelated to study treatments), referrals to outside medical care will be
made. Study medications and all research-related materials and services will be provided at
no cost to participants. Parking vouchers will be provided for all study-related hospital
visits.

The study is investigating 5 potential effects:

1. IGF-1 may improve subjects' behavior, communication and/or mood. In order to measure
this, investigators will evaluate subjects every 5 weeks throughout each treatment
period with behavioral and psychological assessments. All of the tests used during these
evaluations are non-invasive. Investigators will ask parents what their impressions are
about their child's behavior and day-to-day activities through a structured parental
interview and various questionnaires.

2. Investigators will examine subjects' brain function through use of a brain- monitoring
device known as electroencephalography (EEG). The EEG measurements will be taken while
investigators present subjects with exercises to stimulate their vision and hearing. EEG
is a non-invasive way of recording the electrical activity of a subject's brain by
applying a net of monitors (electrodes) to their scalp. Through this method
investigators gain insight into how brain processes visual and auditory stimulus.

3. As one of the features of RTT is unstable vital signs, investigators are trying to
determine if IGF-1 has any effect on normalizing subjects' heart rate and breathing
patterns. To measure this, investigators will ask subjects to wear a non-invasive device
that includes three electrocardiogram connectors and two stretchy bands that wrap around
her chest and abdomen to measure heart rate and respiratory patterns.

4. The safety of IGF-1 in children with RTT is very important. Investigators will ask
parents to complete a medication diary and side effect reporting form on a regular
basis. In addition, laboratory tests will be performed every 10 weeks throughout each
treatment period to evaluate the safety of IGF-1. These will be blood tests similar to
those provided in typical clinical care. Subjects will undergo regular non-invasive
comprehensive physical and neurological examinations, tonsil evaluation,
electrocardiogram (ECG), echocardiogram, scoliosis x-ray, bone age x-ray,
ophthalmological exam, and measurements of height, weight and head circumference.

5. Children with RTT often experience unintended, stereotyped hand movements. The Qsensor®
is a non-invasive device worn on a fabric bracelet that continually measures subjects'
movement. Investigators will use the Qsensor® to determine whether or not IGF-1 affects
the presentation of stereotyped hand movements. As such, investigators will ask subjects
to wear the Qsensor® during study visits every 10 weeks throughout each treatment period
and occasionally at home.

Inclusion Criteria:

- Diagnosis of "classic" (or "typical") Rett Syndrome

- Genetic documentation of MECP2 mutation

- Subject must be post-regression (Hagberg Stage 2)

- Subject and caregiver's primary language must be English

- Subject must reside in North America (US and Canada)

- Caregiver must have internet access and be able to complete questionnaires online and
communicate via email

- Subject is stable on current medications for at least 4 weeks

- Subject's regimen of non-pharmacological interventions (physical therapy, speech
therapy, etc.) is stable for at least 90 days

Exclusion Criteria:

- Severe scoliosis (curvature >40 degrees)

- Bone-age greater than 11 years

- Cardiomegaly (enlarged heart)

- Tanner stage 2 or higher breast development

- Allergy to IGF-1

- Prior use of IGF-1, growth hormone, or sex steroids