The objectives of this trial are: to establish a safety profile for use of Hydroxyurea in
children with Types II and III Spinal Muscular Atrophy; to identify reliable outcome
measures for HU treatment in Types II and III SMA; and to detect the clinical efficacy of HU
treatment in children with Types II and III 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 II (intermediate) SMA has its onset
in early childhood (prior to 18 months) and is characterized by the failure to stand or walk
unassisted. Individuals with Type III SMA (mild SMA or Kugelberg-Welander disease)
typically develop symptoms after 18 months of age and display a wide range of clinical
heterogeneity. The clinical spectrum ranges from rapid progressive weakness resulting in
wheelchair dependence in late childhood to patients being able to walk in adult years and
living productive and independent lifestyles for the majority of their lives.
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 Types II and III SMA. This clinical trial study is intended to establish the safety
profile in children with Types II and III SMA; to identify reliable outcome measures; and to
detect the possible clinical efficacy of HU treatment in children with Types II and III SMA.
Inclusion Criteria:1. Laboratory confirmation of a homozygous deletion or mutation of the
SMN1 gene 2. (Type II) Can sit independently but cannot walk without support by the age of
16 months and never achieve independent walking thereafter; OR (Type III) Can walk
independently within the first 2 years of life, but showing rapid progression of weakness
resulting in the loss of idependent ambulation by 6 years of age 3. Patient is older than
16 months and younger than 8 years old at the time of enrollment
Criteria:1. Known hematological disorders, other systemic disorders, or severe birth
asphyxia 2. Participation in SMA clinical trials for other experimental drugs 3. Requiring
continuous respiratory support before the initiation of HU treatment