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 Sclerosis (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 may need for possible therapy. However, although the potential of combining SCNT technology with ESC research for the future therapies in animals has been demonstrated, it has not yet been accomplished in humans, although members of our team are closing in on this accomplishment. 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 might be ameliorated by insights derived from SCNT-ESC. This proposal marks the beginning of the effort to use human embryonic stem cells (hESC) in a series of experiments whose principle has already been proven in animals and even in early stages in human by members of our team. The focus of our research is to gain a better understanding of ALS. By developing ALS hESC lines, particularly recreating the neuronal niche thought to be awry, researchers will have a novel tool for studying the mechanism of disease. Furthermore, this presumed new model for ALS may also be used to test potential therapies; high throughput screening allows the rapid examination of millions of compounds and may be used to examine gene manipulations and it’s impact on disease. Members of our team have recently reported the first successful derivation of SCNT-embryos from cultured adult cells (skin) in the human. Other members have derived new hESC cell lines under very defined conditions and feel poised to accomplish the next step; the derivation of SCNT derived hESC lines. Upon completion of this project, we may be one step closer to understanding and perhaps stopping the progression of this horrific disease.
Statement of Benefit to California:
The proposed research involves three cutting edge technologies: human embryonic stem cell research, somatic cell nuclear transfer, and patient specific cell lines. 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 tool for developing therapies. 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.