Navigational Chart to the Cures for Heritable Blindness

University of Iowa Institute for Vision Research, 2018

  • Work primarily within a nonprofit, philanthropic culture.

  • Share ideas freely; publish quickly, share detailed methodology when asked.

  • Leave no one behind; work on lots of different diseases (early and late stages) and lots of different genes at the same time.

  • Reduce waste; avoid detailed annual reports, institutional overhead, and unnecessary administrative layers.

  • Work primarily within institutions that are large enough to have the necessary infrastructure to support the work but small enough to allow the close personal involvement of (and real partnership with) institutional leaders at the highest levels.

  • Confine discussions of progress and plans to published papers, formal scientific presentations, scholarly films, and closed meetings with existing and potential major supporters. Avoid engagement in charlatan wars. Avoid becoming the Ponzi police (caveat investor!).

  • Replace animal models with cultured cells whenever possible; use cells for efficacy, animals for safety.

  • Reduce the cost and improve the sensitivity of genetic tests, so that one can find patients who might wish to join trials and, find the remaining disease-causing genes.

  • Develop philanthropically funded GMP facilities to reduce the costs of therapeutic vectors and cells.

  • Employ robotics wherever possible to increase throughput and quality and decrease costs.

  • Develop reusable gene therapy strategies, especially genome editing methods for large and/or expression-sensitive genes.

  • Develop cell therapies based upon patient-derived stem cells, to reduce the risk of immune rejection.

  • Analyze existing clinical data to determine the best timing and anatomic location for therapy.

  • Focus almost entirely on Phase I-II clinical trials with long but fairly conventional follow-up.

  • Carefully evaluate the “better to now” ratio at least quarterly and: 1) avoid changing course for small improvements; 2) avoid delaying clinical deployment of a treatment on the basis of theoretical but currently undemonstrated future improvements; and, 3) be prepared to completely discard any element of the current strategy if a large future benefit in speed (toward the goal) or effectiveness (of the eventual treatments) can be gained by doing so.

  • View every aspect of our work from the perspective of the clinical outcomes we want (and the realities of the diseases we are facing) instead of the perspectives of financial benefit, customary practice, or personal convenience.

  • Do everything with a sense of URGENCY.