About Parkinson’s disease

Affecting more than 10 million people worldwide and one million in the U.S., Parkinson’s disease is the most common neurodegenerative movement disorder in the world. In the U.S., there are approximately 60,000 new Parkinson’s disease diagnoses each year. As many as 90% of Parkinson’s disease cases have no known specific cause, while the remainder show genetic inheritance. The vast majority of patients are diagnosed between the ages 60 and 70, and the incidence increases with age.

Distinguishing features of Parkinson’s disease include resting tremor, rigidity, slowness of movement and postural instability. There are a variety of clinical features that also commonly occur prior to those, including but not limited to sleep disturbances, constipation and behavioral abnormalities.

The underlying pathology is characterized by the degeneration of dopamine-producing neurons connecting areas of the brain called the substantia nigra to a coordinating center for movement called the putamen. The accumulation of α-synuclein protein aggregates as Lewy bodies within the substantia nigra leading to neuronal degeneration and key clinical manifestations.

GDNF gene therapy for Parkinson’s disease

By enhancing levels of a naturally occurring growth factor, glial cell line-derived neurotrophic factor (GDNF) gene therapy is intended to promote the survival and functioning of vulnerable brain cells that degenerate in Parkinson’s disease. Taking advantage of the brain’s own cellular machinery, GDNF gene therapy provides continuous production of GDNF that may provide an advantage over intermittent protein infusions of synthetic GDNF where levels may be subtherapeutic between infusions.

GDNF gene therapy consists of a delivery vector and a specific genetic payload. The vector is made up of the outer shell of the non-infectious adeno-associated virus serotype 2 (AAV2), which provides the carrying capacity and attachment properties to specific brain cell types and transfer of its genetic payload. The genetic payload carried by AAV2 includes a specific DNA sequence (gene) coding for the GDNF protein. Within target brain nerve cells, the GDNF gene induces production and local release of GDNF protein. The genetic payload also includes regulatory sequences that provide long-term stability of the transferred GDNF gene and continuous production of GDNF protein by the recipient nerve cell.

Direct brain delivery of the AAV2-GDNF therapeutic agent is performed with intraoperative MRI guidance using customized neurosurgical methods and technologies. Real-time brain MRI during surgery provides visualization of the distribution of AAV2-GDNF and allows delivery of the therapeutic agent to be tailored to each individual’s precise anatomical requirements.