Appendix 1. Agenda for 1998 Retinal Gene Therapy Workshop

Retinal Gene Therapy Workshop

Emory University Conference Center
Atlanta, Georgia
February 21 and 22, 1998

Organized by William W. Hauswirth and Roderick R. McInnes

Sponsored by the Foundation Fighting Blindness

Saturday, February 21

8:15 PM - Gene Therapy for Inherited Retinal Degenerations: Are you Ready?

Phil Noguchi (Food and Drug Administration)

Sunday, February 22

08:00 AM - Welcome

Jerry Chader (Foundation Fighting Blindness)

08:05 AM - A General Introduction to Inherited Retinal Degenerations

Sam Jacobson - Clinical and Pathological Features
Ed Stone - Genetic Basis of Inherited Retinal Disease

08:35 AM - DNA Viral Vectors

Primary Discussant: Jean Bennett
Secondary Discussants: Battacharya, Gage, Kumar-Singh, Li, Muzyczka

Some Questions: What aspects of DNA viral vectors currently look most favorable in the retina, and why? What are the major problems with these vectors, and what are the most promising approaches for overcoming these problems?

09:10 AM - RNA Viral and Nonviral Gene Delivery

Primary Discussant: Rusty Gage
Secondary Discussants: Bennett, Lewin, Li, Muzyczka, Saperstein

Some Questions: What aspects of RNA viral vectors and nonviral gene delivery currently look most favorable in the retina, and why? What are the major problems with these systems, and what are the most promising approaches for overcoming these problems? How important is regulated expression and how might it be best achieved?

09:50 AM - Alternative Gene Therapies

Primary Discussant: John Flannery
Secondary Discussants: Goff, LaVail, Li, Nickerson, Wong, Zack

Some Questions: Are there useful approaches for more general retinal gene therapy in addition to gene replacement or inactivation of specific dominant negative alleles? Do anti-VEGF, anti-apoptotic factor, neurotrophin, growth factor or cytokine genes offer viable alternative strategies?

10:25 AM - Break

10:40 AM - Animal Models

Primary Discussant: Gus Aguirre
Secondary Discussants: Baehr, Farber, Goff, LaVail, Travis, Valle, Wong

Some Questions: What animal models of retinal diseases are most relevant to clinical disease and which are (or will be) the most convincing as preclinical models. Are additional animal models needed?

11:15 AM - Mechanisms of Retinal Degeneration

Primary Discussant: Don Zack
Secondary Discussants: Aguirre, Baehr, Farber, Flannery, Nickerson, Travis, Wong

Some Questions: What information about general retinal biology is needed to better understand retinal degeneration and cell death? How might this data allow more effective gene therapy strategies?

11:50 PM - Target Human Retinal Diseases

Primary Discussant: Ed Stone
Secondary Discussants: Battacharya, Humphries, Lewis, Sieving, Zack

Some Questions: What human retinal diseases should be first considered for gene therapy, and why? What retinal diseases are (or will be) most amenable to gene therapy approaches? Which need further attention, and at what level?

12:25 PM - Lunch

01:25 PM - Proof of Principle

Primary Discussant: Pete Humphries
Secondary Discussants: Bennett, Flannery, Jacobson, Laties, Sieving

Some Questions: What research milestones must be reached prior to a clinical trial? Are additional experimental results needed? What sorts of retinal injection-related or therapeutic gene-related pathology might be expected in humans? Can this be eliminated or minimized?

02:00 PM - Patient Populations and Clinical Criteria

Primary Discussant: Sam Jacobson
Secondary Discussants: Csaky, Laties, Lewis, Saperstein, Sieving, Stone

Some Questions: What patient populations exist that could be used for Phase I and II retinal gene therapy trials. What ethical and logistical problems can be anticipated? What clinical assays exist for gauging the effectiveness of a retinal gene therapy trial? How could they be employed effectively in a Phase I or II trial? What problems exist?

02:45 PM - Other Human Trials

Primary Discussant: Ric Boucher
Secondary Discussants: Csaky, LaVail, Muzyczka, Noguchi, Verma

Some Questions: What lessons can be learned from other human gene therapy trials?

03:20 PM - Role of Industry

Primary Discussant: Marty Glick
Secondary Discussants: Brazzell, Gonda

Some Questions: What is the current role of industry in retinal gene therapy? What should be done to enhance commercial interest and to increase academic-commercial interactions?

03:55 PM - Break

04:10 PM - Alternatives to In Vivo Gene Therapy

Primary Discussant: Ray Lund
Secondary Discussants: Chader, Csaky, Laties, LaVail, Valle

Some Questions: What is the status of research on transplantation alternatives to retinal gene therapy? Is ex vivo therapy a viable alternative? Are the risk/benefit ratios for alternative therapies predictable and, if so, how do they impact on an overall strategy for treating retinal disease vs. gene therapy?

04:45 PM - Workshop Overview

Primary Discussant: Inder Verma
Secondary Discussants: All participants

Some Questions: Is the field on sufficiently firm scientific footing to bring retinal gene therapy to the clinic in the near future?

05:25 PM - Discussion

06:00 PM - Workshop Adjourns