Walter Kaufmann, MD

Department	Neurology
Hospital Title	Senior Associate in Neurology and Director, Rett Syndrome Program Co-Director, Fragile X Syndrome Program Co-Director, Down Syndrome Program
Academic Title	Visiting Professor of Neurology, Harvard Medical School
Phone	617-355-8994
Fax	617-730-0366
Email	Walter Kaufmann
Location	333 Longwood Avenue Room LO-462 Boston, MA 02115

Research Overview

Using a multidisciplinary approach, I seek to understand the basis of cognitive and behavioral problems in children with genetic disorders associated with intellectual disability and autism. My work includes laboratory investigations of molecular pathways, neuroimaging, animal models of disease and clinical trials of targeted, disease-modifying therapies for Rett syndrome, Fragile X syndrome, Down syndrome and autism spectrum disorders.

Delineating behaviors in neurogenetic disorders

As a behaviorally oriented neurologist, I am interested in characterizing the behavioral phenotypes of Rett syndrome, Down syndrome and Fragile X syndrome, particularly the delineation of autism and other disorders of social interaction in these syndromes. This research involves both standardized behavioral tests and novel, non-clinical tests. I have also made use of web-based databases maintained by patients and families, such as InterRett and the Interactive Autism Network (IAN).

Molecular profiling and neural imaging

Using mouse and other experimental models and neuroimaging data from patients, I study the neural circuitry that underlies the behavioral phenotypes of the above genetic syndromes. I also investigate the genes and proteins involved in their pathogenesis, seeking molecular profiles associated with specific neurobehavioral features – in both the syndromes themselves and in non-syndromic autism and intellectual disability. This work involves brain samples and blood-based biomarkers that correlate with disease variation and severity.

Epigenetics

Building on the discovery that Rett syndrome is associated with abnormalities in methylation of the protein MeCP2, I am also interested in the role of epigenetic mechanisms in developmental disorders, particularly in autism spectrum disorders for which no genetic cause is known.

Clinical trials

I have served as principal investigator or co-investigator on several clinical drug trials for Fragile X, Down syndrome and idiopathic autism. Currently, at Boston Children’s Hospital, I am principal investigator on a trial for IGF-1 therapy for Rett Syndrome. I am also involved in developing behavioral outcome measures and biomarkers for use in these trials.

While current drugs for disorders such as autism are meant only to control symptoms such as anxiety or disruptive behavior, my goal is to help develop treatments that target the underlying biology and improve patients’ core cognitive and behavioral deficits.

About Walter Kaufmann

A native of Santiago, Walter Kaufmann received his medical education at the University of Chile, where he also completed the greater part of a doctorate program in neurobiology and behavioral sciences. After an internship and residency in Chile, he came to Boston for a research fellowship in the dyslexia neuroanatomical laboratory at Beth Israel Deaconess Medical Center, and a residency in anatomic pathology at Boston Children’s Hospital, where he also worked in the Developmental Disabilities Clinic. Later, he completed a residency and fellowship in anatomic pathology and neuropathology at the Johns Hopkins University School of Medicine and joined the Department of Neurology there. He subsequently moved to the Kennedy Krieger Institute, directing the Fragile X Syndrome Clinic and the Center for Genetic Disorders of Cognition & Behavior. He was also a member of the Epigenetics Center at Johns Hopkins.

Dr. Kaufmann is a member of the scientific review board for the International Rett Syndrome Foundation, founder and chair of the The International Consortium of Rett Syndrome Clinical Researchers (RettSearch), and co-founder and co-principal investigator on the Fragile X Clinical and Research Consortium (FXCRC). He is also part of two Work Groups for the forthcoming Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), including one developing guidelines for intellectual disability, autism and other neurodevelopmental disorders. His research is funded by the National Institutes of Health, Autism Speaks, the Department of Defense, the FRAXA Research Foundation, the International Rett Syndrome Foundation and the Centers for Disease Control and Prevention.

Key Publications

Sansome SM, Widaman K, Hall S, Reiss AL, Lightbody A, Kaufmann WE, Berry-Kravis E, Lachiewicz A, Hessl D. Psychometric study of the Aberrant Behavior Checklist in Fragile X syndrome and implications for targeted treatment. J Autism Dev Disord 2011 Oct 5 [Epub ahead of print]

Kaufmann WE, Tierney E, Rohde CA, Suarez-Pedraza MC, Clarke MA, Salorio CF, Bibat G, Bukelis I, Naram D, Lanham DC, Naidu S (2012) Social impairments in Rett syndrome: characteristics and relationship with clinical severity. J Intellect Disabil Res 2012 Mar; 56:233-47.

Ji NY, Capone GT, Kaufmann WE. Autism spectrum disorder in Down syndrome: cluster analysis of Aberrant Behaviour Checklist data supports diagnosis. J Intellect Disabil Res2011 Nov; 55:1064-77.

Mejias R, Adamczyk A, Anggono V, Niranjan T, Thomas GM, Sharma K, Skinner C, Schwartz CE, Stevenson R, Fallin MD, Kaufmann W, Pletnikov M, Valle D, Huganir RL, Wang T. Gain-of-function glutamate receptor interacting protein 1variants alter GluA2 recycling and surface distribution in patients with autism. Proc Natl Acad Sci 2011 Mar 22; 108:4920-25.

Olmos-Serrano JL, Paluszkiewicz SM, Martin B, Kaufmann WE, Corbin JG, Huntsman MM. Defective GABAergic neurotransmision and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of Fragile X Syndrome. J Neurosci 2010 Jul 21; 30:9929-38.

Carter JC, Lanham DC, Pham D, Bibat G, Naidu S, Kaufmann WE. Selective cerebral volume reduction in Rett syndrome: a multiple approach MRI study. AJNR Am J Neuroradiol 2008 Mar; 29:436-41.

For a list of Walter Kaufmann’s publications on PubMed, click here.