The objectives of this trial are: to establish a safety profile for use of Hydroxyurea in
children with Type I Spinal Muscular Atrophy; to identify reliable outcome measures for HU
treatment in Type I SMA; and to detect the clinical efficacy of HU treatment in children
with Type I SMA.
SMA is a neuromuscular disorder characterized by degeneration of spinal cord motor neurons
and muscular atrophy. SMA is classified into three clinical subtypes according to the
severity and age of onset (Types I, II and III). Type I SMA (also called severe, infantile
or acute SMA, or Werdnig-Hoffman disease) is the most severe phenotype. The onset of
symptoms is within the first 6 months of life, and weakness of intercostal muscles and lack
of airway protection lead to respiratory insufficiency and aspiration pneumonia, often
resulting in early infant death.
In our laboratory, our preliminary results indicate that HU treatment significantly
increases both SMN mRNA expression and intact SMN protein levels in vitro. These data
confirm previous observations that in vitro treatments of SMA lymphocytes with hydroxyurea
resulted in augmentation of the SMN2 gene expression in a dose and time related manner.
Based on these exciting pre-clinical data, coupled with the well-documented side-effect
profile of HU in children, we are conducting a pilot clinical trial using HU in children
with Type I SMA. This clinical trial study is intended to establish the safety profile in
children with Type I SMA; to identify reliable outcome measures; and to detect the possible
clinical efficacy of HU treatment in children with Type I SMA.
Inclusion Criteria:1. Laboratory confirmation of a homozygous deletion or mutation of the
SMN1 gene 2. Clinical Diagnosis of Type I SMA (never achieved independent sitting) 3.
Onset of disease before the age of 6 months 4. Enrollment in study within 6 months of
Exclusion Criteria:1. Known hematological disorders, such as chronic anemia (defined as
platelet count less than 100,000/mm^3) in two contiguous measures in two weeks 2. Severe
systemic disorders such as congenital heart disease, other major birth defects involving
internal organs, or severe birth asphyxia 3. Participation in SMA clinical trials for
other experimental drugs 4. Requiring continuous respiratory support before the initiation
of HU treatment