: Spinal muscular atrophy (SMA) is a genetic disease, frequency 8 per 100,000 live births, with a high mortality during infancy and no known treatment. Death is secondary to severe, progressive restrictive lung disease. New information regarding the nature and function of the SMN protein and the availability of new pharmacologic agents now make it possible to consider clinical trials in this disease. The first goal of this project is to perform short term, open label pilot trials of three drugs that have shown promise either in patients or in models of SMA. The trials will be 6 month, open label using riluzole, albuterol and sodium 4-phenylbutyrate. All pediatric age groups from birth to 18 years will be included. Proposed outcome measures depend on age with there being 3 groups: 0 to 2 years, 2 to 5 years and 5 to 18 years. Information regarding tolerability, dosing schedule and administration of these drugs will be important for designing Phase III trials. A Medical Monitor will review parameters for drug toxicity and a Data Safety and Monitoring Committee will protect subjects' safety. The second goal is to correlate biological markers with clinical phenotype, clinical outcome measures and response to therapy. Blood samples for DNA (SMN2 copy count) and SMN mRNA and buccal smear for SMN protein will be obtained. A positive response in biologic markers after treatment will be evidence in favor of advancing to phase III clinical trials. The correlation between biologic markers and clinical outcome measures will aid in determining which drug may be the most likely to show efficacy in a phase III trial. A long-term goal will be to find a biologic measure that might replace cumbersome clinical outcome measures. Thirdly, a parallel study will be conducted to establish validity and reliability of the Peds-QLTM tool in 240 patients who elect not to enter drug trials. The last goal of this continuing proposal is to establish and maintain reliability of the clinical outcome measures for all AmSMART centers using annual inter-rater reliability testing. The Academic Computing Services department at University of Texas Southwestern Medical Center in Dallas will be the Statistics and Data Management Center. This continuing project is an important step toward our ultimate goal of finding an effective treatment for SMA.
| Iannaccone, Susan T; Hynan, Linda S; Morton, Anne et al. (2009) The PedsQL in pediatric patients with Spinal Muscular Atrophy: feasibility, reliability, and validity of the Pediatric Quality of Life Inventory Generic Core Scales and Neuromuscular Module. Neuromuscul Disord 19:805-12 |
| Kaufmann, Petra; Iannaccone, Susan T (2008) Clinical trials in spinal muscular atrophy. Phys Med Rehabil Clin N Am 19:653-60, xii |
| Finkel, Richard S; Hynan, Linda S; Glanzman, Allan M et al. (2008) The test of infant motor performance: reliability in spinal muscular atrophy type I. Pediatr Phys Ther 20:242-6 |
| Iannaccone, Susan T (2007) Modern management of spinal muscular atrophy. J Child Neurol 22:974-8 |
| Iannaccone, Susan T; Smith, Stephen A; Simard, Louise R (2004) Spinal muscular atrophy. Curr Neurol Neurosci Rep 4:74-80 |
| Iannaccone, Susan T; Hynan, Linda S; American Spinal Muscular Atrophy Randomized Trials (AmSMART) Group (2003) Reliability of 4 outcome measures in pediatric spinal muscular atrophy. Arch Neurol 60:1130-6 |
| Iannaccone, Susan T; American Spinal Muscular Atrophy Randomized Trials (AmSMART) Group (2002) Outcome measures for pediatric spinal muscular atrophy. Arch Neurol 59:1445-50 |
