Recombinant DNA Advisory Committee- 9/12-13/94 
Committee Motion 
Dr. Erickson made a motion to approve the protocol to treat 2 adult patients with the 
only other stipulation being a follow-up after the 12 month period of study. Dr. Saha 
seconded the motion. Ms. Meyers added that follow-up should be life long. 
The RAC approved a motion made by Dr. Erickson and seconded by Dr. Saha to accept 
the protocol submitted by Dr. Chester B. Whitley, University of Minnesota, Minneapolis, 
Minnesota, by a vote of 15 in favor, 1 opposed, and no abstentions. RAC approval is 
contingent on the following: (1) the protocol will be limited to 2 adult subjects, and (2) 
patients will be monitored for the presence and expression of the transduced gene for over 
1 year following their participation in the study. 
Summary 
Dr. Chester B. Whitley, University of Minnesota, Minneapolis, Minnesota, may conduct 
gene transfer experiments on two adult subjects (over 18 years of age) with mild Hunter 
syndrome (Mucopolysaccharidosis Type II). The autologous peripheral blood lymphocytes 
will be transduced ex vivo with a retroviral vector, L2SN, encoding the human cDNA for 
iduronate-2-sulfatase (IDS). The transduced lymphocytes will be reinfused into the 
patients on a monthly basis. The study will determine the frequency of peripheral blood 
lymphocyte transduction and the half-life of the infused cells. Evaluation of patients will 
include measurement of blood levels of IDS enzyme, assessment of metabolic correction 
by urinary glycosaminoglycan levels, clinical response of the disease, and monitoring for 
potential toxicity. This Phase I study is to demonstrate the safety of the L2SN-mediated 
gene therapy and to provide a preliminary evaluation of clinical efficacy. 
XV. CLARIFICATION ON NIH/FDA CONSOLIDATED REVIEW/DR WALTERS. 
Dr. Walters made a clarification regarding the motion concerning the NIH/FDA 
consolidated review voted for approval by the RAC. The motion included the necessary 
changes in the NIH Guidelines indicated in the proposed action to allow initial submission 
of the application to FDA Dr. French Anderson inquired about when will the change 
taking place. Dr. Walters said that the guideline changes have to be approved by the NIH 
Director before they are effective. Dr. Wivel added that until that time, the old system 
will stay in place. Dr. Walters’ clarification was accepted by Dr. Miller, who made the 
motion, and by the RAC. 
XVI. REPORT FROM THE WORKING GROUP ON RETROVIRUS VECTORS/DR WTVEL 
On September 7, 1994, the Working Group on Retrovirus Vectors held a telephone 
conference call to discuss the letter dated December 2, 1993, submitted by the late Dr. 
Howard Temin regarding the adequacy of current methods to detect RCR. The Working 
Group members were Drs. Walters, Miller, Straus, Parkman and Brinckerhoff. Dr. Wivel 
summarized the discussion. Dr. Temin asked in his letter, if new RCR are generated by 
recombination of viral RNA sequences, would such recombinant RCR be detectable by 
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