Table of Contents
Background on Gene Therapy
Many diseases are driven by genetic mutations in which the mutated genes can affect the production of proteins. Gene therapy attempts
to address disease biology by introducing recombinant DNA into a patient's own cells, commonly in the form of a functional copy of the patient's defective gene, to address the genetic defect and
modulate protein production and cellular function, which provides therapeutic benefit.
gene therapy, physicians can introduce or re-introduce genes that encode a therapeutic protein. Instead of providing proteins or other therapies externally and dosing them over a
long period, we believe gene therapy offers the possibility of dosing a patient once to achieve a long-term, durable benefit. Gene therapies are typically comprised of three elements: a transgene, a
promoter and a delivery mechanism such as our AAV9 capsid. Once the therapeutic gene is transferred to a patient's cells, we believe the cells may be able to continue to produce the therapeutic
protein for years or, potentially, the rest of the patient's life. As a result, gene therapy has the potential to transform the way these patients are treated by addressing the underlying genetic
Background on Spinal Muscular Atrophy
SMA is a severe neuromuscular disease characterized by the loss of motor neurons leading to progressive muscle weakness and paralysis.
The incidence of SMA is approximately one in 10,000 live births, and one in 50 people are carriers of the SMA gene (approximately six million Americans). SMA is generally divided into sub-categories
termed SMA Type 1, 2, 3 and 4. SMA, and the SMA sub-types, are diagnosed first by identifying the existence of a genetic defect in the SMN1 gene and then determining the number of copies of the
SMN2 backup gene, which correlates with disease onset and severity. If insufficient protein is expressed, muscles do not develop properly. Approximately 60% of