For Immediate Release     June 5, 2000

Contact: info@asgt.org

Stem Cell Research Shows Promising Future in Gene Therapy

Denver, CO (June 3, 2000) - Gene therapy researchers reported on innovative approaches to insert genes into cells called hematopoietic stem cells, which divide to produce the wide variety of blood cells. The scientists discussed this research at a press conference today held in conjunction with the American Society of Gene Therapy's 3rd Annual Meeting in Denver, CO.

"Gene therapy is in its infancy as a biomedical science," commented said ASGT President, Savio L. C. Woo, PhD, Professor and Director of the Institute for Gene Therapy and Molecular Medicine at the Mount Sinai School of Medicine, NY. "In order to realize its full potential to treat a variety of diseases in the future, much basic science research and pre-clinical studies will need to be pursued. The work presented here is a promising beginning."

The following summaries of presented material reflect the most up-to-date information in gene therapy research.

---

"Multiple Cycles of ex vivo Therapy for X-Linked Chronic Granulomatous Disease (CDG) Sustain Production of Oxidase-normal Blood Neutrophils"
Presenter: Harry Malech, National Institutes of Health, Bethesda, MD

Chronic Granulomatous Disease (CGD) is an inherited form of immune deficiency in which there is a defect in neutrophil proteins that are critical for fending off disease. One gene therapy approach is to isolate the cells that give rise to all the types of blood cells (including neutrophils) from patients with this defect, introduce the normal genes for these proteins, and transfuse the "corrected" cells back into the patients, a process known as "ex vivo" gene therapy. These precursor cells, also known as hematopoietic stem cells, can be isolated based on specific chemical "tags" on their surface.

H. Malech and his collaborators used this approach in treating patients with an X-linked form of CGD (X-CGD), which accounts for approximately 65% of all cases. They isolated the hematopoietic stem cells from four X-CGD patients, infected the cells with a retrovirus containing the normal gene (in this case, the gp91phox subunit of an enzyme called phagocyte oxidase), grew the transformed cells in culture, and infused them back into the original patients from which the cells were derived. The patients all received two to 4 tansfusions separated by 2 months or more. Three of the four patients had sustained and continuous production of normal neutrophils for 6 to 14 months. Of even greater interest, although still not understood, is the finding that two of the patients who had liver infections that resisted cure by conventional methods resolved during the course of treatment. This suggests that this gene therapy approach could also be effective in treating CGD patients with severe intractable infections, although more targeted studies need to be done.

---

"Multilineage Transduction of Non-human Primate CD34+ Hematopoietic Cells Using RD-114-pseudotyped Oncoretroviruses"
Presenter: P.F. Kelly, St. Jude Children's Research Hospital, Memphis, TN

Although retroviruses are attractive vectors for many reasons, their utility is reduced by the fact that they have difficulty infecting non-dividing cells or cells that lack the appropriate receptor proteins on their surface. Thus, much effort has gone into "engineering" retroviruses to get them to target cell types they normally are unsuccessful at infecting. One particular cell type of interest is the hematopoietic stem cell, the precursor cell that gives rise to the multiple cell types that make up the blood.

P.F. Kelly and his colleagues discovered that they could take a particular retrovirus coat protein (RD114) from a feline retrovirus, put it on the surface of another retrovirus (a process called "pseudotyping"), and successfully introduce the gene for a green fluorescent protein marker into hematopoietic cells isolated from a non-human primate. When the researchers transfused these altered cells back into the monkey, they found that, over time, a large number of different blood cells (various types of T cells, NK cells, B cells, platelets, etc.), were "tagged" with the fluorescent marker. In other words, the hematiopoietic cells were successfully transduced with the new gene to levels that could have clinical impact (i.e., if a therapeutic gene was used). This work suggests that retroviral transduction of human hematopoietic stem cells is now possible.

---

The ASGT is the largest medical professional organization representing researchers and scientists dedicated to discovering new gene therapies. ASGT was established in 1996, and has grown to over 2,400 members. It is committed to promoting and fostering the exchange and dissemination of information and ideas related to gene therapy, encouraging the general field of research involving gene therapy and to promoting professional and public education in all areas of gene therapy.

 ###