ASGT Press Release 

New research shows the effectiveness of gene therapy to treat genetic diseases,
from the ASGT 8th Annual Meeting

RNAi as a potential treatment for Huntington's disease

ST. LOUIS - A study using RNA interference to reduce the toxic effects associated with Huntington's disease was presented today at the 8th Annual Meeting of the American Society of Gene Therapy (ASGT) in St. Louis.

Huntington's disease (HD) is a fatal, dominant neurodegenerative disorder caused by a gene mutation of the protein huntingtin. Therapies for Huntington's disease are often targeted at reducing the disease's toxic effects, or other properties of the mutant protein. Gene therapy using RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing their expression.

A research team led by Beverly L. Davidson, PhD, University of Iowa, tested if RNAi was effective in reducing the disease gene in mice and the associated HD-like symptoms. They found that RNAi reduced the mutant huntingtin levels to 40% compared to control treated mice, resulting in improved motor skills. The therapy also reduced the clumps of mutant protein in brain cells that is characteristic of this class of diseases.

A partial reduction of the mutant huntingtin had a significant impact on the cellular and motor disease in this animal model of Huntington's disease. The data provides support for further development of RNAi for treating diseases such as Huntington's.

Gene therapy successful in treating metachromatic leukodystrophy

A study reporting the results of gene therapy for the disease metachromatic leukodystrophy was presented today at the 8th Annual Meeting of the American Society of Gene Therapy (ASGT) in St. Louis.

Metachromatic leukodystrophy (MLD) is a lethal genetic disease that mainly affects children between 1 and 6 years of age. It is estimated that MLD occurs in 1 out of 40,000 births. MLD is caused by a deficiency of the enzyme arylsufatase A (ARSA), resulting in the accumulation of toxic metabolites in the affected tissues, particularly in the nervous system. No effective treatment is available.

However, Allesandra Biffi and Luigi Naldini, and colleagues from the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy, tested the safety and efficacy of hematopoietic stem cells (HSC) to deliver the therapeutic ARSA enzyme to the affected tissues in mice, which closely resemble the human pathology.

Their research found that HSC gene therapy protected the mice from the major symptoms associated with MLD, including learning and coordination abnormalities. They observed almost complete clearance of toxic metabolites in the affected tissue. Their research provides the first evidence of direct delivery of the ARSA enzyme to the nervous system by the route of the blood cells. These results offer a potential future treatment for MLD patients.

Induced neurogenesis successful in treating Huntington's disease

A study showing the use of induced neurogenesis as a potential therapy for treating Huntington's disease was presented today at the 8th Annual Meeting of the American Society of Gene Therapy (ASGT) in St. Louis.

Neurodegenerative diseases, such as Huntington's diseases, result from genetically programmed degeneration of brain cells, called neurons, in certain areas of the brain, causing uncontrolled movements, loss of intellectual faculties and emotional disturbance.

Sung-Rae Cho, MD from Dr. Steve Goldman's lab at the University of Rochester Medical Center, and colleagues, sought to determine if induced neuro genesis could delay the progression of Huntington's disease in mice. Neuro genesis is the process of adding neurons to the brain.

They injected mice with adenoviruses containing brain-derived neurotrophic factor (BDNF) and noggin, whose combination was previously shown to increase the number of neurons recruited to the neostriata of normal adult rats. This is the part of the brain mediating motor coordination and is affected in conditions such as Huntington's and Parkinson's disease. Researchers found that the mice treated with the growth factors underwent substantial neurogenesis, resulting in a delay of their disease progression and motor impairment, and extended survival.

The American Society of Gene Therapy is a professional non-profit medical and scientific organization dedicated to the understanding, development and application of gene and related cell and nucleic acid therapies and the promotion of professional and public education in the field.

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