Clinical and Neuropsychological Investigations in Batten Disease

Summary

Principal Investigator: Jonathan Mink
Abstract: The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are inherited, autosomal recessive lysosomal storage diseases. Although the NCLs are relatively rare, the childhood variants represent the most common neurodegenerative disorders of childhood, affecting approximately 1:25,000 in the U.S. and with an incidence worldwide as high as 1:12,500. NCL variants are distinguished mainly by their different ages of onset and the rate at which symptoms progress. Juvenile NCL (JNCL), due to the CLN-3 mutation, is one of the more common forms of NCL. Symptom onset for JNCL is between ages 5 to 8, with slow progression until death in the 2nd or 3rd decade of life. The most common early symptoms of JNCL are vision loss, seizures dementia, behavioral difficulties, and impaired motor skills. As the disease progresses, the child becomes increasingly disabled and there is a substantial caregiver burden. There are few quantitative data on the natural history of JNCL. It is known that JNCL includes a broad range of neurological, neuropsychological, and behavioral/psychiatric symptoms. There is progressive loss of speech, language, motor skills, and self-care skills as the disease progresses. In some individuals, aggressive behavior, anxiety, hallucinations, obsessions, or personality changes are prominent. However, it is not known to what degree each type of symptoms contributes to the overall disability and caregiver burden. It is also not known to what degree the seizures and seizure control contributes to disability. Further, it is not known to what extent genotype influences phenotypic variability. We propose three specific aims to determine the natural history of JNCL quantitatively, to characterize the neuropsychological and behavioral phenotype of JNCL, to establish validity and reliability of a rating scale for JNCL, and to determine correlations between phenotype and genotype of individual JNCL subjects. Successful completion of this project will provide the necessary framework for moving forward with clinical trials in this devastating disease. Although JNCL is a rare disease, our research has implications that can be generalized to the study of other degenerative neurologic disorders in children and for preparing translational clinical trials in these diseases.
Funding Period: ----------------2007 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Clinical trials in rare disease: challenges and opportunities
    Erika F Augustine
    Department of Neurology, University of Rochester Medical Center, Rochester, New York, NY, USA
    J Child Neurol 28:1142-50. 2013
  2. pmc Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease)
    Heather R Adams
    University of Rochester Batten Center Study Group, University of Rochester School of Medicine and Dentistry, Department of Neurology, Rochester, New York, NY, USA
    J Child Neurol 28:1128-36. 2013
  3. pmc Batten disease: clinical aspects, molecular mechanisms, translational science, and future directions
    Sarah Bianca Dolisca
    Department of Pediatrics, Georgia Regents University, Augusta, GA 30912 3700, USA
    J Child Neurol 28:1074-100. 2013
  4. pmc Classification and natural history of the neuronal ceroid lipofuscinoses
    Jonathan W Mink
    Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
    J Child Neurol 28:1101-5. 2013
  5. pmc Methodology of clinical research in rare diseases: development of a research program in juvenile neuronal ceroid lipofuscinosis (JNCL) via creation of a patient registry and collaboration with patient advocates
    Elisabeth A de Blieck
    University of Rochester, Rochester, NY 14642, USA
    Contemp Clin Trials 35:48-54. 2013
  6. ncbi NCL diseases - clinical perspectives
    Angela Schulz
    Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Biochim Biophys Acta 1832:1801-6. 2013
  7. pmc Females experience a more severe disease course in Batten disease
    Jennifer Cialone
    University of Rochester, Rochester, NY, USA
    J Inherit Metab Dis 35:549-55. 2012
  8. pmc Quantitative telemedicine ratings in Batten disease: implications for rare disease research
    J Cialone
    University of Rochester, Rochester, NY, USA
    Neurology 77:1808-11. 2011
  9. pmc Quantifying physical decline in juvenile neuronal ceroid lipofuscinosis (Batten disease)
    J M Kwon
    University of Rochester, Rochester, NY, USA
    Neurology 77:1801-7. 2011
  10. pmc Parent-reported benefits of flupirtine in juvenile neuronal ceroid lipofuscinosis (Batten disease; CLN3) are not supported by quantitative data
    Jennifer Cialone
    University of Rochester, Rochester, NY 14642, USA
    J Inherit Metab Dis 34:1075-81. 2011

Scientific Experts

  • Patricia Dickson
  • Jennifer M Kwon
  • Jonathan W Mink
  • Erika F Augustine
  • Jennifer Cialone
  • Heather R Adams
  • Elisabeth A de Blieck
  • Frederick J Marshall
  • Amy Vierhile
  • Heather Adams
  • Nicole Newhouse
  • Sarah Bianca Dolisca
  • Angela Schulz
  • Paul G Rothberg
  • J Cialone
  • Jonathan Mink
  • Leon Dure
  • Ruth Williams
  • Mitali Mehta
  • Katherine Rose
  • David A Pearce
  • Alessandro Simonati
  • Bernard L Maria
  • Alfried Kohlschütter
  • Denia Ramirez-Montealegre
  • Leon S Dure
  • Erika Levy
  • Katherine R Rose
  • A Vierhile
  • J W Mink
  • F J Marshall
  • N Newhouse
  • E F Augustine

Detail Information

Publications11

  1. pmc Clinical trials in rare disease: challenges and opportunities
    Erika F Augustine
    Department of Neurology, University of Rochester Medical Center, Rochester, New York, NY, USA
    J Child Neurol 28:1142-50. 2013
    ..Solutions to these barriers will require multicenter collaboration, partnership with patient organizations, training a new generation of researchers interested in rare diseases, and leveraging existing resources. ..
  2. pmc Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease)
    Heather R Adams
    University of Rochester Batten Center Study Group, University of Rochester School of Medicine and Dentistry, Department of Neurology, Rochester, New York, NY, USA
    J Child Neurol 28:1128-36. 2013
    ....
  3. pmc Batten disease: clinical aspects, molecular mechanisms, translational science, and future directions
    Sarah Bianca Dolisca
    Department of Pediatrics, Georgia Regents University, Augusta, GA 30912 3700, USA
    J Child Neurol 28:1074-100. 2013
    ....
  4. pmc Classification and natural history of the neuronal ceroid lipofuscinoses
    Jonathan W Mink
    Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
    J Child Neurol 28:1101-5. 2013
    ..Better knowledge of the natural histories of these disorders is necessary to shed light on the underlying pathobiology and to develop new therapeutics. ..
  5. pmc Methodology of clinical research in rare diseases: development of a research program in juvenile neuronal ceroid lipofuscinosis (JNCL) via creation of a patient registry and collaboration with patient advocates
    Elisabeth A de Blieck
    University of Rochester, Rochester, NY 14642, USA
    Contemp Clin Trials 35:48-54. 2013
    ..True for many rare diseases, there are no treatments that impact the course of JNCL. The University of Rochester Batten Center's (URBC) mission is to find treatments to slow, halt, or prevent JNCL...
  6. ncbi NCL diseases - clinical perspectives
    Angela Schulz
    Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Biochim Biophys Acta 1832:1801-6. 2013
    ..This article is part of a Special Issue entitled: The neuronal ceroid lipofuscinoses or Batten Disease. ..
  7. pmc Females experience a more severe disease course in Batten disease
    Jennifer Cialone
    University of Rochester, Rochester, NY, USA
    J Inherit Metab Dis 35:549-55. 2012
    ..Future research in sex differences in JNCL may help to further understand the biological mechanisms underpinning the disease course and may point to targeted therapies...
  8. pmc Quantitative telemedicine ratings in Batten disease: implications for rare disease research
    J Cialone
    University of Rochester, Rochester, NY, USA
    Neurology 77:1808-11. 2011
    ..To determine if remote administration of the Unified Batten Disease Rating Scale (UBDRS) Physical Impairment subscale by telemedicine is reliable and feasible across a broad range of disease severity...
  9. pmc Quantifying physical decline in juvenile neuronal ceroid lipofuscinosis (Batten disease)
    J M Kwon
    University of Rochester, Rochester, NY, USA
    Neurology 77:1801-7. 2011
    ..Now that therapies are being proposed to prevent, slow, or reverse the course of JNCL, the UBDRS will play an important role in quantitatively assessing clinical outcomes in research trials...
  10. pmc Parent-reported benefits of flupirtine in juvenile neuronal ceroid lipofuscinosis (Batten disease; CLN3) are not supported by quantitative data
    Jennifer Cialone
    University of Rochester, Rochester, NY 14642, USA
    J Inherit Metab Dis 34:1075-81. 2011
    ..However, our quantitative, prospectively obtained data did not show any change in JNCL disease progression that could be attributed to flupirtine. This study highlights the need for prospective experimental therapeutic research...
  11. pmc Research challenges in central nervous system manifestations of inborn errors of metabolism
    P I Dickson
    Department of Pediatrics, LA Biomedical Research Institute at Harbor UCLA, 1124 W Carson St, HH1, Torrance, CA 90502, USA
    Mol Genet Metab 102:326-38. 2011
    ..Scientific, ethical and regulatory issues are discussed, along with ways to measure outcomes and the conduct of clinical trials. Participants included regulatory and funding agencies, clinicians, scientists, industry and advocacy groups...