Spinal muscular atrophy (SMA) is a disorder that affects the motor neurons. SMA is caused by
a mutation in a part of the DNA called the survival motor neuron (SMN1) gene, which normally
produces a protein called SMN. Because of their gene mutation, people with SMA make less SMN
protein, which results in the loss of motor neurons. SMA symptoms may be improved by
increasing the levels of SMN protein. The purpose of this study is to determine whether a
drug called a histone deacetylase inhibitor can increase SMN levels.
After undergoing a general medical and neurological evaluation, study participants will
donate a blood sample. Researchers will use this sample to measure SMN levels. They will also
isolate cells from the blood and treat the cells with various drugs that may increase SMN
Spinal muscular atrophy (SMA) is a currently untreatable, autosomal recessive motor neuron
disease that is caused by deficiency of full-length survival motor neuron (SMN) protein. One
promising therapeutic approach to SMA is to pharmacologically increase full-length SMN
protein levels. Several compounds have been shown to increase SMN levels in immortalized cell
lines derived from SMA patients. The objective of this study is to determine baseline SMN
levels in primary peripheral blood cells of SMA patients and heterozygous carriers compared
to unaffected controls and to investigate the effects in vitro of pharmacological compounds
that are expected to increase SMN levels. It is anticipated that these studies will provide
further evidence to support the use of one or more of these compounds in a clinical trial for
SMA patients. The study population will include patients with genetically proven type I, II,
or III SMA and their family members. Blood samples from anonymous, unaffected control
patients will be obtained through the department of transfusion medicine (99-CC-0168). This
is an investigative study that involves blood drawing only. No new therapy will be provided
except the standard of care.
- INCLUSION CRITERIA:
Diagnosis of SMA with genetically proven mutations in the SMN1 gene or unaffected family
members (age greater than or equal to 2 years).
No exposure to valproic acid or any other HDAC inhibitors for a period of at least 2 weeks.
Written, informed consent (and assent, if applicable).
History of valproic acid or other HDAC inhibitor use within the past14 days.
History of bleeding disorder, which would make a blood draw unsafe.