Drug Delivery Technology

rejection. As a result of these concerns, an FDA advisory committee was held in April 2008 to determine the safety of developing cellular therapies from human embryonic stem cells and whether these products could be safely tested in humans. A main concern raised was the ability of embryonic stem cells to generate teratomas –– tumor formations containing tissue from all three germ layers. Evidence indicates that teratomas may arise from the administration of embryonic stem cells that have not been fully differentiated. Furthermore, some experts have stated that because some embryonic stem cell therapies may contain a heterogenous mixture of cells with different degrees of differentiation, there is a possibility that these cells may migrate and differentiate into inappropriate cells.

Adult Stem Cells: A
Good Alternative?

Critics against embryonic stem cell research claim that adult stem cells may offer the same potential. Although less flexible then their embryonic counterpart, adult stem cells are multipotent. This means that they can produce different types of related cells. In the body, adult stem cells primarily help maintain homeostasis and assist in the repair of damaged tissues. This less controversial option is closer to the market than embryonic stem cells, with several late-stage adult stem cell products in development.

Although used therapeutically for the past 30 years in the form of bone marrow transplants, adult stem cells have some limitations that complicate their comparison to their embryonic counterpart. Despite the fact that they

are found in many different tissues, including adipose tissue, liver, and blood, adult stem cells are relatively rare and hard to isolate in large amounts. Historically, they have been difficult to culture because they stop dividing and lose potency over time. As a result of these challenges, adult stem cell therapies were thought of as products that could only be produced in limited quantities using cells obtained from one or more donors for each patient needing treatment.

New innovations in adult stem cell culture have allowed some companies to develop adult stem cell therapies that do not have these constraints. One such company is Athersys, Inc., a biopharmaceutical company that is developing a novel stem cell product called MultiStem that contains multipotent adult progenitor cells (MAPC). MultiStem does not have product limitations seen in other adult stem cell products. This product has benefits, such as the ability to be made from stem cells obtained from a single donor and may be produced on a large scale, allowing the development of a standardized pre-made product. Additionally, most adult stem cells have the ability to develop into a limited number of cell types and tissues. MultiStem, however, has been found to exhibit a broad plasticity and is able to form a large number of different cell and tissue types, giving this product a promising therapeutic potential.

Vol 9 No 6

JUNE 2009

On the Road to
Clinical Trials
In January 2009, Geron announced
that the FDA had approved its
investigational new drug application
(IND) for GRNOPC1, making this the

first human embryonic stem cell therapy to begin human clinical trials. Additionally, it signifies the start of a potential new class of therapies and paves the way for more of these therapies to start clinical trials. GRNOPC1, made from oligondendrocyte progenitor cells derived from human embryonic stem cells, is being developed to restore spinal cord function. For Geron, this announcement represents over a decade of research. Moreover, it represents the clearance of many significant challenges, including an earlier hold on the start of clinical trials by the FDA.

Geron plans to start human clinical trials for GRNOPC1 later this year using patients who have documented evidence of complete spinal cord injury. This therapy will be injected into the injury site within 7 to 14 days after the injury occurs. Results from animal studies indicate that GRNOPC1 is safe and does not exhibit evidence of teratoma formation. In addition, these studies show that this product could improve locomotor activity in a variety of different animals.

Advanced Cell Technology, a biotechnology company focused on developing stem cell therapies for regenerative medicine, hopes to follow Geron in forming human clinical trials for its embryonic stem cell product. The company is expected to file an IND for its product, retinal pigmented epithelial (RPE) cell therapy, later this year. RPE is being developed as a treatment of retinal degenerative diseases like age-related macular degeneration. To help initialize the process, Advanced Cell Technology has already completed a pre-investigational New Drug meeting regarding the requirements.