To date, most basic and applied research on human disease is performed with animal models, the majority being mice. Unfortunately, most of what is learned from mouse models is not associated with human disease. Moreover, even with current advanced genetic technology, it is nearly impossible to generate models of rare diseases such as Amyotrophic Lateral Scelerosis (ALS), also known as Lou Gehrig’s disease.
“Therapeutic Cloning” will provide a novel opportunity to study patient specific stem cells allowing one to understand the genetic causes of disease. It is a process known as somatic cell nuclear transfer (SCNT) in which the nucleus of a donor cell is transferred into an egg that has been emptied of its chromosomes. That egg now contains an exact duplicate of the donor's genome, and if all goes well when it is cultured in incubator for five to seven days, an SCNT-embryo will develop into a stage in the incubator for derivation of embryonic stem cells (ESC) which can differentiate into any cell type a patient my need for possible therapy. However, although the potential of combining SCNT technology with ESC research for the future therapies in animals has been demonstrated; there is little data demonstrating its feasibility in humans.
While we understand and respect those who oppose SCNT-ESC research, we are equally sincere in our belief that the life-and-death medical needs of suffering children and adults will be ameliorated by SCNT-ESC work. This proposal marks the beginning of the effort to use human embryonic stem cells in a series of experiments whose principle has already been proven in animals. In our proposed research, we initially aim at understanding ALS following establishment of SCNT-ESC lines. However, there have been no reports of successfully generating SCNT-embryos from cultured adult cells in the human. Therefore, initial development and validation of the lab procedures for embryo development following cloning procedures needs to be accomplished. In our proposed research, we will use depository eggs donated by infertile couples undergoing in vitro fertilization who have had successful therapy and do not wish to keep frozen eggs for future replacement, which will be discarded. Frozen eggs as well as somatic cells from ALS patients will be obtained with informed consent in a controlled and scientific manner. Based on our proven record with successful SCNT in animal studies, we have reasoned that ESC lines can be established from SCNT-embryos which will be genetically identical to ALS patients’ own cells using frozen human eggs.
Upon completion of this project, we will be able to prove the concept of SCNT-ESC research for the development of novel therapies for the treatment of human diseases. Furthermore producing such stem cell lines will provide a novel resource to the biomedical research community to study and understand how genes correlate with the development of disease.
Statement of Benefit to California:
The proposed research involves three cutting edge technologies: embryonic stem cell research, somatic cell nuclear transfer and gene modification. These technologies which are complementary to each other, have yet to be developed and optimized in humans, and when combined, will offer great potential in medicine. The ability to stay close to emerging technologies is paramount to keeping California business at the leading technological edge. In addition to the likely economic benefits to the State of such a commercial program, it is critical to point to the paramount medical benefits to the public of such collaboration in terms of the development of milestone medical therapies for future cell therapy.
Upon completion of this project, we will be able to prove the concept of SCNT-ESC research as a future therapy for numerous diseases. In addition, stem cells derived from SCNT-embryos will likely be a conduit to drug-development, eventually leading to new pharmaceuticals. Furthermore, producing such stem cell lines would establish a novel resource to study the role of individual genes in disease development. With the improvement of cloning methodologies as described in our proposal, SCNT-ES cells could be used as a cellular transplantation resource. Cell therapy technologies overlap with those of gene therapy, cancer vaccines, drug delivery, tissue engineering and regenerative medicine. Collectively, the value of the cell-based markets is estimated to be $26.6 billion in 2005, $56.2 billion in 2010, and $96.3 billion in 2015. The largest expansion will be in diseases of the nervous system and cancer. Skin and soft tissue repair as well as diabetes mellitus will be other major markets. The number of companies involved in cell therapy has increased remarkably during the past few years. In 2006, more than 500 companies have been identified to be involved in cell therapy. Of these, 104 are involved in stem cell therapy.
If the proposed research is successful as anticipated in contributing to the development of cell therapy products, there are likely to be substantial benefits to two critical sectors of the California economy, health care and pharmaceuticals. Additionally, our proposed research will benefit through further refinement and expansion of its SCNT-ESC technology and through collaboration in other areas of biotechnology, including molecular biology and immunobiology. Furthermore, the advancement of ESC research together with SCNT technique will enhance partnership developing programs for start-up as well as established biotechnology companies. Support for this project will help maintain our leadership in embryonic stem cell and cloning technologies and will help a California business to be better equipped to compete for a multi-billion dollar market.