Measuring Levels of SMN in Blood Samples of SMA Patients

Spinal Muscular Atrophy Clinical Trial

Official title:

SMN Levels in Peripheral Blood Samples of SMA Patients and the Effects of Pharmacological Compounds In Vitro

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00061607
• Other study ID #: 030203
• Secondary ID: 03-N-0203
• Status: Completed
• Phase: N/A
• First received: May 29, 2003
• Last updated: October 5, 2017
• Start date: May 19, 2003
• Est. completion date: April 4, 2017

Study information

• Verified date: April 4, 2017
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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 levels.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: April 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

• 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).

EXCLUSION CRITERIA:

History of valproic acid or other HDAC inhibitor use within the past14 days.

History of bleeding disorder, which would make a blood draw unsafe.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Crawford TO, Pardo CA. The neurobiology of childhood spinal muscular atrophy. Neurobiol Dis. 1996 Apr;3(2):97-110. Review. — View Citation

Nicole S, Diaz CC, Frugier T, Melki J. Spinal muscular atrophy: recent advances and future prospects. Muscle Nerve. 2002 Jul;26(1):4-13. Review. — View Citation

Pearn J. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. J Med Genet. 1978 Dec;15(6):409-13. — View Citation