Interventions for Reading Disabilities in NF1
Interventions for Reading Disabilities in NF1
Neurofibromatosis Type 1 (NF1) is a common genetic disorder that is associated with a four
 times greater risk of learning disabilities, including reading disabilities, and a deficiency
 of neurofibromin - a protein important in a signaling pathway that regulates learning and
 memory. Our previous work (NS49096) demonstrated that school-age children with NF+RD can
 respond to standard phonologically-based reading tutoring originally developed to treat
 reading disability in the general population. Combining our work with that by other
 researchers suggesting that a medication (Lovastatin) may counteract the effects of the
 deficient neurofibromin, and possibly ameliorate learning disabilities in NF1, the
 investigator propose to examine the synergistic effects of medication plus reading tutoring.
Neurofibromitosis Type 1 (NF1) is a common autosomal dominant neurocutaneous syndrome. The
 most common concern of NF1 is learning disabilities (LDs). Approximately half of children
 with NF1 have LDs, the most common of which are reading disabilities (RDs).The purpose of
 this research is to gain a deeper understanding of the characteristics and treatment of RDs
 in NF1.

 The Investigator will evaluate four different groups (see list below) to determine if there
 are differential outcomes in these groups of children with NF+RD. The first two groups will
 consist of NF1 patients, and the second two groups will consist of participants with RDs but
 without NF1.

 1. Reading tutoring program and a medication called Lovastatin (NF1 patients)

 2. Reading tutoring program and no Lovastatin (placebo) (NF1 patients)

 3. Reading tutoring program (RD participants)

 4. Other Academic "Sham" tutoring (eligible to receive reading tutoring after study
 participation is complete) (RD participants)
Inclusion Criteria:

 This study will be open to all English speakers who meet eligibility criteria regardless of
 race, gender, minority or socioeconomic status. Inclusion criteria to be met are listed
 below:

 1. Individuals ages 8-20 (all participants)

 2. Documented NF-1 (NF patients only)

 3. If female, participant is post-menarche (NF patients only)

 4. If male, participant has reached Tanner Stage 2 (NF patients only)

 5. Participant able to swallow capsule (NF patients only, may be confirmed via
 swallowability test, described below)

 6. Participant's English is sufficient for school (all participants)

 7. Participant must either answer "yes" to question A, or answer "yes" to at least 2
 items for questions B-D listed below:

 A. Has your child ever been diagnosed with a reading disability? B. Did your child have
 trouble learning how to "sound out" words? C. Have you (parent) ever been concerned about
 your child's reading ability? D. Did the school or teacher ever express any concerns about
 your child's reading ability? Swallowability Assessment: We may ask patients to perform a
 capsule swallowability assessment prior to enrollment. We will ask subjects to attempt to
 swallow an empty capsule, matching the same size of the Lovastatin 20mg and 40mg capsules
 to be used in the study, to confirm swallowability. Patients will be provided with up to 2
 capsules as needed to successfully perform the swallowability assessment. If the patient is
 unable to swallow the capsule, enrollment in the study may deferred or declined.

 A child will be excluded if he/she meets any of the following criteria, which will be
 determined by initial telephone screening as well as review of medical/developmental
 history prior to and during testing:

 1. Child 7 years of age or less;

 2. known uncorrectable visual impairment;

 3. documented hearing impairment greater than or equal to a 25 dB loss;

 4. medical contraindication to MRI procedures (e.g., metal devices);

 5. any psychiatric, behavioral, or developmental disorder that would preclude active
 participation in in-depth tutoring sessions

 6. Pregnant at time of screening.

 7. Known conditions which are contraindicated to Lovastatin

 1. Hypersensitivity to the medication

 2. Uncontrolled Epilepsy

 3. Metabolic Syndrome X, High Blood Sugar,

 4. Muscle Damage Due to Autoimmunity

 5. Stroke caused by Bleeding in the Brain, Loss of Memory,

 6. Severely Low Blood Pressure

 7. Liver Problems including Abnormal Liver Function Tests

 8. Severe Renal Impairment,

 9. Serious Muscle Damage that may Lead to Kidney Failure,

 10. Recent Operation or significant Injury

 11. Muscle Pain or Tenderness with Increase Creatinine Kinase,

 12. Habit of Drinking Too Much Alcohol

 13. Pregnant or lactating. - Lovastatin is contraindicated during pregnancy and in
 nursing mothers because it decreases synthesis of cholesterol and other products
 of the cholesterol biosynthesis pathway that are essential components for fetal
 development.

 Children who meet criteria for ADHD, Oppositional Defiant Disorder, adjustment disorder,
 and/or mild depression will be eligible as long as they are not taking psychotropic
 medications, with the exception of stimulant medication for ADHD.

 For pilot participants only:

 Criteria for inclusion/exclusion for pilot participants is outlined below. Children who
 meet criteria for ADHD, Oppositional Defiant Disorder, adjustment disorder, and/or mild
 depression will be eligible as long as they are not taking psychotropic medications, with
 the exception of stimulant medication for ADHD.

 1. Children ages 8-17

 2. Participant is a native English speaker

 3. Participant must either answer "yes" to question A, or answer "yes" to at least 2
 items for questions 2-4 listed below:

 A. Has your child ever been diagnosed with a reading disability? B. Did your child have
 trouble learning how to "sound out" words? C. Have you (parent) ever been concerned about
 your child's reading ability? D. Did the school or teacher ever express any concerns about
 your child's reading ability?

 A child will be excluded if he/she meets any of the following criteria, which will be
 determined by initial telephone screening as well as review of medical/developmental
 history prior to and during testing:

 1. Children 7 years of age or younger

 2. previous diagnosis of Intellectual Disability;

 3. known uncorrectable visual impairment;

 4. documented hearing impairment greater than or equal to a 25 dB loss;

 5. medical contraindication to MRI procedures (e.g., metal devices);

 6. known IQ below 70;

 7. a pervasive developmental disorder; and

 8. any known neurologic pathology, including epilepsy, spina bifida, cerebral palsy,
 traumatic brain injury, optic gliomas, and brain tumors (other than UBOs).

 9. Comorbid severe psychiatric disorders will also be excluded.