Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy

Participation in this study entails six visits and seven to eight blood draws over 13
months. Each visit entails a stay of two days and one night at the General Clinical Research
Center (GCRC).

Subjects who live within driving distance will be allowed to participate in the study
without an overnight stay through two consecutive outpatient visits. All subjects will be
evaluated at two screening visits 2-4 weeks apart to determine eligibility for
participation. Eligible subjects will be randomized to receive VPA or placebo for the first
six months. At the six-month visit, patients will be evaluated and crossed over to the other
regimen.

Inclusion Criteria:

1. Ambulatory adults with SMA 3 ages 18-60. The diagnosis of SMA must be documented by
the homozygous deletion of both SMN1 genes on standard genetic tests for the
disorder. Patients must be able to walk thirty feet without assistance (i.e. no
canes, walkers).

2. Interest in participating and the ability to meet the study requirements.

3. Women of child bearing age are required to be on birth control or abstain while
participating in the study.

Exclusion Criteria:

1. Non-ambulatory type 3 adults and all type 2 adults.

2. Patients with co-morbid conditions that preclude travel, testing or study
medications.

3. Patients who have participated in a treatment trial for SMA in the 3 months prior to
this trial, or plan on enrolling in any other treatment trial during the duration of
this trial.

4. Patients who are, in the investigator's opinion, mentally or legally incapacitated
from providing informed consent for the study, or are otherwise unable to meet study
requirements or cooperate reliably with study procedures, especially strength
testing.

5. Patients with a need for non-invasive ventilatory support (e.g. BiPAP) for > 12
hours/day

6. Transaminases, amylase or lipase > 3.0 x normal values, WBC < 3.0 or neutropenia <
1.0, platelet count < 100 K, or hematocrit < 30 persisting over a 30 day period

7. Use of medications or supplements which interfere with VPA metabolism and increase
the potential risks of the medications, or are hypothesized to have a beneficial
effect in SMA animal models or human neuromuscular disorders within 3 months of study
enrollment. These agents include riluzole, creatine, butyrate derivatives, growth
hormone, anabolic steroids, daily albuterol use, anticonvulsants, or other HDAC
inhibitors.

8. Women who are pregnant or who intend to become pregnant while participating in the
research study or who are breastfeeding.