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Sakkubai Naidu, MD

Sakkubai Naidu, MD

Dr. Naidu received her M.B.B.S. from the Madras Medical College (MMC), India, in 1962. This was followed by two years as Intern and House Surgeon at the Government General Hospital in Madras, a year as Tutor in Physiology and another as Tutor in Anaesthesiology at MMC. She obtained additional experience in anaesthesiology in Baden, Switzerland prior to completing three years of pediatric training at Coney Island and Kings County Hospitals in Brooklyn. Her interest in neurology had first been awakened by exposure to neuroscience – particularly neuroanatomy — during medical school. Two pediatric neurologists she encountered during pediatrics training – Drs. Kytja Voeller and Stuart Brown – proved crucial influences in her decision to train in child neurology, which she completed at Albert Einstein. During those three years of training Dr. Isabelle Rapin expanded Dr. Naidu’s interests and accomplishments to include neonatal neurology, metabolic and genetic diseases, behavioral and learning disorders, neuropsychology, and degenerative conditions.

Other individuals who played important roles in her training and clinical career development were Drs. Alfred Spiro (neuromuscular diseases), Leslie Wolfson (movement disorders), and Jerome Engel (epilepsy and clinical research). Throughout an extended phase of career development another critical element in the achievement of Dr. Naidu’s remarkable success was the support and encouragement she received from her husband, Kamalakar Naidu, including his unstinting commitment to support and encourage his wife and care for their children during periods of great demands upon his wife’s time and energy despite the demands of his own career as a nuclear engineer. Three children have blessed their marriage – son Ajit, who is now a cardiologist, son Joey, who developed a large-scale landscape business, and daughter Anuradha, who has also become a physician.

Upon completion of her training, Dr. Naidu remained for several years on the faculty at Albert Einstein, followed by two years at the University of Illinois. She then spent seven years at Loyola University Stritch School of Medicine, where she served as Director of the MDA clinic, consultant for the Gilles de la Tourette Society, and Chief of Child Neurology. Dr. Naidu achieved board certification in electroencephalography in 1982, then pursued fellowship training in neonatal EEG/neurology at Port Royal Hospital, Paris, France, in 1983. Her early research concentrations included the role of taurine in childhood epilepsy, the effects of aspartame on early developing brain, neuro-developmental effects of intraventricular neonatal hemorrhage, and the efficacy of clorazepate in treatment of epilepsy. In 1984 she was recruited as Joseph P. Kennedy Jr. Foundation Scholar and member of the faculty at Johns Hopkins and the Kennedy Krieger Institute.

At Hopkins Dr. Naidu formed a particularly close and remarkably productive relationship with Dr. Hugo Moser. Both manifested a remarkably similar capacity for enlisting the collaborative efforts of individuals from diverse professional backgrounds to advance the understanding of pathogenesis, treatment, and outcome of neurological illnesses. The origin of this force was the strong desire to improve the lot of children and their families, with the guiding principle of engaging the efforts not only of individuals possessing the specialized skills of clinical evaluation not limited to the nervous system – including individual biologists, chemists, radiologists, geneticists, and others – but also to alter the direction of whole laboratories and combine the efforts of other research programs. That this rare quality has persisted as an important element of Kennedy Krieger’s leadership in the study of genetically determined neurological diseases after Dr. Moser’s passing is due in no small measure to Dr. Naidu – perhaps something that Dr. Moser foresaw. Thus, in addition to extraordinary devotion to patient care and other academic commitments, Dr. Naidu has maintained her well-planned research efforts.

At Hopkins Dr. Naidu concentrated on leukodystrophic conditions (peroxisomal varieties as well as ascertaining the causes and providing definitions for those of “unknown etiology”), genetic causes of mental retardation, neuronal ceroid lipofuscinosis, and Rett syndrome. She has achieved international standing in all of these areas with efforts and achievements ranging from elucidating pathogenesis and refining clinical descriptions to meticulous clinical trials. To date, Dr. Naidu and her associates have contributed 142 original papers to the peer-reviewed literature. It is a challenging task to report within the compass of this sketch the breadth and depth of these papers. The most striking observation is to note that sixty-eight of these papers concern almost every imaginable aspect of Rett syndrome, a condition concerning virtually all aspects of which Dr. Naidu is among the world’s leading experts. Dr. Naidu was named Director of the Neurogenetics Unit of the Kennedy Krieger in 1989 and attained the rank of Professor in 2000.

Dr. Naidu’s capacity to master all aspects of the neurological problems that engage her interest is exemplified by the fact that her knowledge of Rett syndrome ranges from the behavior, breathing dysregulation, bloating, and constipation of girls with this illness to the complex details of the genetics of the condition and its impact on mechanisms of glutamate receptor density and trafficking. Dr. Naidu has been known, in the apparent attempt to accelerate the rate of progress of understanding, to acquire the bench top skills of molecular genetics. She has published forty-one papers concerning leukodystrophic conditions – particularly those due to peroxisomal dysfunction – but also conditions ranging from Alexander, Krabbe, or Canavan to disappearing white matter and other newly recognized entities in need of definition and further ensuing study. Included among other metabolic conditions upon which she has devoted her attention are studies shedding important light on glycogen storage diseases, non-ketotic hyperglycinemia, neuronal ceroid lipofuscinoses, and Lesch-Nyhan. Eight papers concern movement disorders, five epilepsy, four consider neonatal neurological subjects.

In order to properly gauge the impact of these papers it is worth considering that where most peer-reviewed papers remain uncited or cited only a few times, 83 of these papers have been cited more than ten times, 28 more than fifty times, and ten have been cited more than one-hundred times (a mark rarely achieved in predominantly clinical papers). The most highly cited papers concern dietary therapy for ALD, the neuroanatomy of Rett syndrome, phenotype correlations of peroxisomal complementation groups, localization of Rett syndrome to the Xq28 gene, plasma VLCFA abnormalities of peroxisomal disease patients, MECP2 mutations with and without Rett syndrome phenotype, two publications concerning the elF2B mutation and the pathogenesis of vanishing white matter, and the role of CpG hotspots in spontaneous and familial MeCP2 mutations “in Rett syndrome and beyond” (250 citations). It must not be forgotten that many papers for which there are fewer citations have played very important roles in clinical evaluation and management of patients. Such clinical studies tend to generate fewer citations but may, as her papers have done, provide such a wealth of well worked out detail as to represent the current “last word” on such topics. Dr. Naidu has participated in the publication of forty important and thoughtful chapters that are similarly richly informative, as first or senior author of most.

Dr. Naidu’s extraordinary enthusiasm has drawn numerous individuals under her wings, individuals whose promise she has recognized, mentored, supported, and whose devotion to science she has successfully encouraged. Her ability to enlist and combine the efforts of individuals ranging from the freshest trainee to senior clinicians and scientists from a range of disciplines may best be exemplified by her efforts concerning Rett syndrome. Her engagement of the diverse talents of many individuals who were not intending to study this syndrome enabled her not only to refine clinical understanding, but also to engage Eric Hoffman’s efforts to localize the Rett gene to Xq28 by the study of a particular carefully selected family (Sirianni et al); this subsequently led to the demonstration in the Zoghbi laboratory (Amir et al.) of MeCP2 mutation in Rett syndrome. The Narayanan laboratory was then recruited to generate the first MeCP2 knock-in (A140V mutation) mouse model, with further work underway to attempt the same feat for the R270X mutation. Dr. Naidu is a remarkable judge of the potential of other individuals, whether or not they have recognized such capacity in themselves.

Dr. Naidu’s advocacy for patients and families with rare diseases is matched by her enthusiasm for the encouragement of the development of child neurology in India and elsewhere in the world. She is the leader of the Indian/Southeast Asian community of the CNS. Dr. Naidu has served as an Examiner for the ABPN since 1980. A role model for women, she is really no less a role model for men in child neurology. Her interests outside of medicine are also broad. They include Indian culture and carnatic music, she is a superb cook and a devoted gardener, and an aficionado of theater and art. Her own family has remained a very important center of her life, around which her other families – patients, trainees, colleagues, and admirers – regularly gather.