Current Environment:

Research Overview

Dr. Levy directs a clinical research group that is studying the effect of innovative therapies for phenylketonuria (PKU). His group has examined the role of cofactor therapy for stimulating phenylalanine hydroxylase (PAH) and is currently a major site for a clinical trial of alternative enzyme therapy of PKU. Dr. Levy is also an investigator for the national study of the natural history and treatment of urea cycle disorders, a study examining brain imagining in PKU, and a study to determine the feasibility of next generation sequencing in newborn screening.

Laboratory Projects

  1. Cofactor Therapy for PKU: Dietary therapy has been enormously successful in PKU, converting a disease that produced intellectual disability into a disorder that can result in normal growth and development. However, the diet is extremely difficult and because of this most adults and many adolescents do not follow the diet as required, resulting in long-term problems. Some individuals with PKU respond to megadoses of sapropterin dihydrochloride, a synthetic form of tetrahydrobiopterin (BH4), with increased activity of PAH, the defective enzyme in PKU. This results in a lower phenylalanine level and greater tolerance of natural foods, alleviating some of the difficulties of the diet. Our ongoing work is in examining the benefits and long-term results of cofactor treatment in PKU.
     
  2. Alternative Enzyme Therapy for PKU:Phenylalanine ammonia lyase (PAL) is an enzyme that has been found to metabolize phenylalanine in a different direction from the natural pathway that is blocked in PKU. Consequently, this enzyme reduces the blood phenylalanine level in those with PKU and may serve as therapy for PKU, perhaps substituting for the difficult diet. Ongoing studies are examining this therapy to determine if it is safe and offers long-term treatment for PKU.

Research Background

Dr. Levy obtained his M.D. degree from the Medical College of Georgia. Following residences in Pediatrics and Pediatric Pathology at Boston City Hospital, Columbia- Presbyterian Medical Center in New York, and Johns Hopkins Hospital in Baltimore, he served a fellowship in Metabolism under Drs. Mary Efron and Hugo Moser at the Massachusetts General Hospital. Subsequently, Dr. Levy was on the faculty at the Massachusetts General Hospital and also served as Consultant and then Director of the Massachusetts Metabolic Disorders Program. When the New England Newborn Screening Program was established, Dr. Levy became the Chief of Biochemical Genetics.

In 1978, Dr. Levy moved to Boston Children’s Hospital as Director of the Metabolic Program where he expanded the program from a PKU clinic to inborn errors of metabolism, and at the same time directed the New England Maternal PKU Program. Dr. Levy has served as Chair of the Workgroup on Newborn Screening and Follow-Up and Chair of the Newborn Screening Translational Research Network for the American College of Medical Genetics. He is a reviewer for many leading medical journals, is on the Editorial Board of the International Journal of Neonatal Screening, has served on several research advisory boards, is a consultant for several laboratories that are developing new metabolic treatments, has published over 450 peer-reviewed articles on metabolic disorders, and has received a number of national and international awards and honors for research in newborn screening and biochemical genetics.

Selected Publications

  1. S.E. Waisbren, F. Rohr, V. Anastasoaie, M. Brown, D. Harris, A. Ozonoff, S. Petrides, A. Wessel, H.L. Levy. Maternal Phenylketonuria: Long-term Outcomes in Offspring and Post-pregnancy Maternal Characteristics. JIMD Rep. 2015;21:23-33. doi: 10.1007/8904_2014_365. Epub 2015 Feb 25.
  2. Landau YE, Lichter-Konecki U, Levy HL. Genomics in newborn screening. J Pediatr, 2014;164:14-9.
  3. Levy HL, Milanowski A, Chakrapani A, Cleary M, Lee P, Trefz F, Whitely C, Feillet F, Feigenbaum A, Bebchuk J, Christ-Schmidt H, Dorenbaum A, for the Sapropterin Research Group. A Phase-III randomized placebo-controlled study of the efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6-BH4) in reducing phenylalanine levels in subjects with phenylketonuria. Lancet, 2007; 370:504-10.
  4. Levy HL, Burton B, Cederbaum S, Scriver C. Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH4) in phenylketonuria and its use in treatment. Molec Genet Metab, 2007;92:287-91.

Publications