Antioxidant Therapy With N-acetylcysteine for Children With Neurofibromatosis Type 1

Children with neurofibromatosis type 1 (NF1) commonly suffer from the effects of cognitive, behavioral, and motor impairments. At present, there is no specific treatment for this NF1 complication. In this project, the investigators will assess the safety and clinical benefit of N-acetylcysteine (NAC) as a pharmacological intervention in children with NF1. This drug choice is based on the recent findings from mouse models to study the central nervous system manifestations of NF1 at Cincinnati Children's Hospital Medical Center (CCHMC). These findings revealed a role for myelin-forming oligodendrocytes in the control of nitric oxide synthases (NOS) and their product, nitric oxide (NO), in maintenance of brain structure and function, including regulation of behavior and motor control. Treating these mice with NAC corrected cellular and behavioral abnormalities. This data from animal models of NF1 along with uncontrolled clinical observations in children with NF1 suggest that the antioxidant compound, NAC, may reduce these impairments. Therefore, the investigators propose performing a single center double-blind placebo controlled, prospective, Phase II study to explore safety, tolerability, and efficacy of NAC on motor behavior and/or learning in children with NF1 aged 8 through 16 years old. Participants will be carefully monitored for side effects. Primary and secondary outcome measures will be administered at baseline, follow-up, and post-treatment.

Inclusion Criteria ѱ: You can be in this study if you have any of the following: 1. Males and females older than 8 years and younger than 16 years old 2. Has a diagnosis of NF1 (neurofibromatosis type 1) 3. Has an abnormal PANESS score 4. Has an intelligence quotient (IQ) at or above 70 5. Participants on stimulant or any other psychotropic medication should stay on a stable dose (no change in dose) for at least 30 days before entering the study and maintain that dose while in the study Exclusion Criteria: You cannot be in this study if you have any of the following: 1. Younger than 8 years or older than 16 years ѱ 2. Do not have a diagnosis of NF1 ѱ 3. IQ below 70 ѱ 4. Had a dose change of any stimulant or psychotropic medication in the last month (30 days) ѱ 5. Are being treated with chemotherapy or had chemotherapy in the last 6 months 6. Have epilepsy ѱ 7. High risk of upper gastrointestinal (GI, the stomach and the small and large intestine) hemorrhage (bleeding). Examples: presence of esophageal varices or peptic ulcers 8. Active intracranial lesions (abnormality found on brain imaging such as an MRI) (stable low-grade glioma is acceptable) or epilepsy diagnosis ѱ 9. Have Major Depression, Bipolar Disorder, Conduct Disorder, Adjustment Disorder, other major Anxiety Disorders, or other developmental psychiatric diagnoses, based on history. ADHD is allowed. 10. For females, pregnancy 11. Is currently using antidepressants, dopamine blocking agents, or mood stabilizers 12. Have any of the following medical devices: implanted brain stimulator, vagal nerve stimulator, ventriculoperitoneal (VP) shunt, cardiac pacemaker, or implanted medication port ѱ 13. Asthma (bronchospasm has been reported as occurring infrequently and unpredictably when NAC is used as a mucolytic agent) 14. Current use of MEKINIST (MEK-inhibitor) or use within 30 days ѱ Indicates Inclusion/Exclusion Criteria for the treatment- and non-treatment cohorts (no mark indicates exclusion requirements for the 12-week treatment-cohort only).