History: Prepare a 200- to 300-word history about the National Critical Technology (NCT) technical application your team has selected to solve a local or national problem.

Examples of Research: Cite three detailed examples of research done in the past 3 to 5 years which focused on the NCT technical application your team selected. Include: the funding agency, the principal investigator's name, and the institution where the research is or was being conducted.

Scientific Advancemetns: Based on the research your team has done, explain how the NCT application chosen has advanced scientific knowledge.

The first approved gene therapy procedure was performed on September 13, 1990. Ashanti DeSilvia was a four year old who had severe combined immune deficiency (SCID); she had a very weak immune system that couldn’t fight off a minor viral infection like influenza or chicken pox. Children who have SCID usually develop overwhelming infections and hardly ever live to be adults. Their only hope before 1990 was to be treated with massive amounts of antibiotics, but this has limited results. To help Ashanti, the doctors took some of her white blood cells and inserted the gene that her cells were missing. Then they grew a sufficient amount of new genetically engineered white blood cells and injected them in her blood stream. Her immune system improved enough for her to get out of the sterile environment of her home, go to school, and live the life normal children get to live.

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, has been extensively studied in mice. In 2000, studies showed that gene therapy can extend the life of mice by 30%. While these are promising results, scientists say that it will take at least 5 years before a medicine to treat ALS in humansbecomes available.

Some critics have said that there should never be any form genetic manipulation, regardless of how well intentioned. Some say that somatic (non reproductive) cell therapy should be allowed, but germ (reproductive) cell therapy that might have a harmful affect on future generations. And the supporters of gene therapy say that with the proper regulations and precautions, germ-like therapy is a reasonable addition of the advancement made to date, and an ethically acceptable procedure.

Researches at John Hopkins University and the Salk Institute found that by injecting a gene into mice that promoted muscle growth slowed the normal process of muscle degeneration and preserved nerve cells. This type of gene therapy doubled the mice's life span. The research was lead by Fred H. Gage, professor of genetics, Salk research Brian Kaspar, and Jeffrey Rothstein, professor of neurology at Johns Hopkins University. The researchers showed that nerve cells could be preserved by injecting a adeno-associated virus that carried DNA with a gene that causes the production of IGF-1(insulin growth factor-1) into muscles. IGF-1 then activates Akt, an enzyme which slows programmed cell death.

"This animal study is the first to identify a treatment that slows the disease once symptoms have already appeared, a significant finding that offers insight into the disease mechanism and important therapeutic potential." - Jeffrey Rothstein

Dr. Thomas Jessell is researching a possible treatment for people affected with A.L.S. The focus of the study is a protein known as Hedgehog, which promotes motor neuron formation in stem cells. This study was done in collaboration with Curis Inc. and Project A.L.S. By locating a protein that can significantly help the repair neurons in the brain, it is now possible to synthesize DNA with the gene that makes this protein. This makes it possible for patients to receive gene therapy. The hopes of the study were that a new drug could be developed to regenerate motor neurons, which degenerate in A.L.S. patients.

“The recent study (funded by Project A.L.S. and published by Dr. Thomas Jessell and his associates of Columbia University in collaboration with Curis scientists) demonstrating that stem cells can be converted into motor nerve cells by the addition of Hedgehog, is very encouraging. While a great deal more research needs to be done, the collaboration with Project A.L.S. and its investigators will provide significant insight into the therapeutic potential of the Hedgehog pathway as a treatment option for A.L.S.” - Dr. Lee Rubin, Curis’ Chief Scientific Officer

Researchers at the University of California have found that correcting deficient glia cells, cells that support the motor neurons, can significantly suppress the effects of ALS. They created a mouse model with ALS. Then they successfully treated the glia cells in the mouse using techniques of gene therapy, and slowed the onset of ALS. Researchers believe not only that this discovery could improve the quality of life for people with ALS, but that this task of supplying the patient with normal support cells could completely prevent motor neuron degeneration.

“These results raise hope for a potential new treatment for ALS patients, however, further studies in animals and clinical trials in patients will be needed.” - Erik Storkebaum