Project 1

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Project 1:
DEVELOPMENT OF CLINICAL OUTCOME MEASURES IN NEURONAL CEROID LIPOFUSCINOSES – NEW TOOLS FOR EVALUATION OF EXPERIMENTAL THERAPIES

 

Project leader
Dr. med. Angela Schulz

 


Project Summary

Neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative diseases in childhood. They are characterized by dementia, visual loss, epilepsy, motor decline, and premature death. No cure is currently available.

First experimental therapy studies are being developed for three NCL forms such as gene therapy and enzyme replacement therapy. However, their evaluation is difficult as the clinical course of NCLs can be variable. This has already been shown using established retrospective clinical scoring systems. However, in order to closely and prospectively monitor disease progression in patients under experimental therapies, additional more detailed and also organ specific evaluation systems are necessary.

This project seeks to develop such outcome measures by (i) improving existing retrospectively used clinical scoring systems for prospective follow-up examinations and (ii) correlating these with organ specific evaluations such as MRI-based brain volumetrics, cardiologic and ophthalmologic examinations.

Data will be collected in the already developed international DEM-CHILD NCL patient database which has been established as part of the European FP7-project DEM-CHILD (funding period 10/2011-09/2014). It contains retrospectively collected clinical data derived from more than 500 NCL patients from 12 participating countries which can be used for statistical correlation in order to develop prospective quantitative clinical outcome measures in NCLs.

These data will contribute to the preparation of trials with newly emerging therapies by follow up of a large cohort of NCL patients.

 

Progressive brain atrophy in a patient with CLN2 disease at age 3.5 years and 5 years.

 

References

  1. Schulz A, Ajayi T, Specchio N, et al. (2018) Study of Intraventricular Cerliponase alfa for treatment of CLN2 disease. New Engl J Med DOI:10.1056/NEJMoa1712649
  2. Löbel U, Sedlacik J, Nickel M, Lezius S, Fiehler J, Nestrasil I, Kohlschütter A, Schulz A. (2016) Volumetric description of brain atrophy in neuronal ceroid lipofusincosis 2: Supratentorial gray matter shows uniform disease progression. Am J Neuroradiol 37:1938-43