Crawford TO From enigmatic to problematic: the new molecular genetics of childhood spinal muscular atrophy. Neurology. 1996 Feb;46(2):335-40. Review.
Czeizel A, Hamula J A hungarian study on Werdnig-Hoffmann disease. J Med Genet. 1989 Dec;26(12):761-3.
Emery AE Population frequencies of inherited neuromuscular diseases--a world survey. Neuromuscul Disord. 1991;1(1):19-29. Review.
Evangeliou A, Vlassopoulos D Carnitine metabolism and deficit--when supplementation is necessary? Curr Pharm Biotechnol. 2003 Jun;4(3):211-9. Review.
Feldkötter M, Schwarzer V, Wirth R, Wienker TF, Wirth B Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet. 2002 Feb;70(2):358-68. Epub 2001 Dec 21.
Fischer U, Liu Q, Dreyfuss G The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell. 1997 Sep 19;90(6):1023-9.
Merlini L, Stagni SB, Marri E, Granata C Epidemiology of neuromuscular disorders in the under-20 population in Bologna Province, Italy. Neuromuscul Disord. 1992;2(3):197-200.
Tein I, DiMauro S, Xie ZW, De Vivo DC Valproic acid impairs carnitine uptake in cultured human skin fibroblasts. An in vitro model for the pathogenesis of valproic acid-associated carnitine deficiency. Pediatr Res. 1993 Sep;34(3):281-7.
Tein I, Xie ZW Reversal of valproic acid-associated impairment of carnitine uptake in cultured human skin fibroblasts. Biochem Biophys Res Commun. 1994 Oct 28;204(2):753-8.
Thurston JH, Hauhart RE Amelioration of adverse effects of valproic acid on ketogenesis and liver coenzyme A metabolism by cotreatment with pantothenate and carnitine in developing mice: possible clinical significance. Pediatr Res. 1992 Apr;31(4 Pt 1):419-23.
Van Wouwe JP Carnitine deficiency during valproic acid treatment. Int J Vitam Nutr Res. 1995;65(3):211-4.
Multi-center Phase II Trial of Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy (SMA CARNI-VAL Trial)
Interventional studies are often prospective and are specifically tailored to evaluate direct impacts of treatment or preventive measures on disease.
Observational studies are often retrospective and are used to assess potential causation in exposure-outcome relationships and therefore influence preventive methods.
Expanded access is a means by which manufacturers make investigational new drugs available, under certain circumstances, to treat a patient(s) with a serious disease or condition who cannot participate in a controlled clinical trial.
Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.
Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.