• Subproject 1
  Prof. Dr. med. E. Zrenner
• Subproject 2
  Prof Dr. med., Dipl.-Ing. Mathias W. Seeliger
  Dr. rer. nat Regine Mühlfriedel
  Prof. Dr. rer. nat. Uwe Wolfrum
• Subproject 3
  Prof. Dr. rer. nat. Bernhard Weber
• Subproject 4
  Prof. Dr. rer. nat Bernd Wissinger
  (Principal Investigator)
  Dr. rer. nat. Susanne Kohl
• Subproject 5
  Dr. rer. nat. Marius Ueffing
  Dr. rer. nat. Stefanie Hauck
• Subproject 6
  Dr. Christine Wallrapp
• Subproject 7
  Dr. rer. nat. Thomas H. Wheeler-Schilling,
  Franz Badura

Disease Progression assessed by novel Markers and Therapeutic Windows in various Types of Human Cone-Rod Dystrophies

• Prof. Dr. med. Eberhart Zrenner (Principal investigator),
  Center for Ophthalmic Research
  Institute for Ophthalmic Research, Tuebingen, Germany
  http://www.fia.uni-tuebingen.de/zrenner

Objective

• Obtaining genotypically and phenotypically well-characterized cohorts of cone-rod dystrophies
• Identifying highly sensitive markers of progression as a tool for observing the therapeutic effect in regards of safety and efficacy in treatment trials.

Summary

Cone-rod dystrophies are a heterogeneous group of genetic retinal disorders and in most cases lead to severe visual impairment. Rescue of cone function is the most important for good vision in daily human life and the major target in therapeutic approaches. The phenotype spectrum of clinically defined cone-rod dystrophies is notably broad and currently, there are no sensitive markers to observe disease progression, allowing the proper timing of possible treatment intervention or monitoring safety and efficacy in human therapeutic trials.

Subproject 1 is focused on longitudinal investigation of a large cohort of patients affected by cone-rod dystrophies (with M. Stargardt and achromatopsia patients as group of particular interest). The acquired data are expected to provide novel insights regarding the understanding of cone-rod function interdependence, identifying the criteria for estimating the disease natural history and progression rate. It is of central importance for the development of effective treatment modalities aimed at rescuing cone function and preserving and/or restoring vision.

The primary goal is focused on the obtaining of genotypically and phenotypically well characterized cohorts of cone-rod dystrophies with identified highly sensitive markers of progression as a tool for observing the therapeutic effect in regards of safety and efficacy in treatment trials. The primary goal will be utilized within the following tasks:

1. To develop and utilize early diagnostic tests for the modelling the natural history of CRD with a special care given to study photoreceptors in patients with CRD.
2. To quantify the initiation and progression rate of the CRD in a precisely specified cohort and to define the most significant predictive markers of the disease progression.
3. To identify the subtle markers to observe and validate the gene therapy benefits and to assess the neuroprotective therapeutic windows for CRD in humans.
4. To create user-friendly database of phenotype-genotype associated CRD patients' cohort for registering the patients (pseudoanonymous form) suitable for therapeutic trials.