Mitigating the clinical consequences of genetic mutations that affect the developing nervous system

The research conducted in the Colleen Giblin Research Laboratories (http://www.giblinlabs.org/) located on the 9th floor of the Neurological Institute has been determined by my clinical responsibilities as a child neurologist and Director Emeritus of the Pediatric Neurology Service. The research themes have focused on a group of genetically-determined diseases that affect the developing nervous system. This system includes the brain, spinal cord, peripheral nerves and skeletal muscles. These diseases can destroy the structure and the function of a complex system that ultimately determines the fundamental domains of cognition, social behavior and movement. The immature nervous system is unduly vulnerable to mutations that are scattered throughout the human genome. Arrest or regression of neurological development are common clinical outcomes associated with these mutations, and effective treatments for these relatively common disorders are sadly lacking. Our ultimate goal is to craft effective treatments that will allow these unsuspecting children to rid themselves of their symptoms and realize their full neurological potential. We have invested considerable time and energy investigating three diseases that are emblematic of these basic tenets: Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes (MELAS), Glucose Transporter Type1 Deficiency Syndrome (Glut1DS) and Spinal Muscular Atrophy (SMA). Each disease has devastating effects on the developing nervous system; each is genetically determined, and each has little or no effective treatment. Our research themes address the need (1) to better understand basic disease mechanisms, (2) to create experimental models that faithfully recapitulate the human condition, (3) to improve our understanding of phenotype-genotype correlations, and (4) to identify epigenetic factors that will mitigate disease expression. The child neurology clinical research enterprise receives grant support from federal and non-federal sources including the National Institutes of Health, the Spinal Muscular Atrophy Foundation, the Colleen Giblin Foundation, the Will Foundation and the Muscular Dystrophy Association. Funding from the SMA Foundation supports patient care provided in the SMA Clinic and research that is conducted in the multi-institutional Pediatric Neuromuscular Clinical Research (PNCR) Network for SMA Clinical Trials. The PNCR Network brings together outstanding clinical investigators at four leading academic institutions in the Northeast and provides an opportunity for patients with SMA in this region of the United States to actively participate as research participants in a search for the cure of this devastating childhood motor neuron disease.

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