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Mixed Phase II Results With Gene Therapy in Parkinson’s Disease

Treatment fails to meet primary endpoint (Apr. 19)

Mixed results have been announced from a phase IIb trial of CERE-120 (adeno-associated virus [AAV]–neurturin; Ceregene, Inc.), a gene therapy product designed to deliver the neurotrophic factor neurturin, in patients with Parkinson’s disease (PD). The study did not demonstrate statistically significant efficacy on the primary endpoint (Unified Parkinson's Disease Rating Scale [UPDRS]–motor off). However, one of the key secondary endpoints (daily diary–off score) showed a statistically significant benefit. The trial also provided evidence for the safety of CERE-120 and the dosing methods employed.

A marked placebo effect was observed in that both the sham-surgery control patients and those treated with CERE-120 showed significant improvement after their surgery.

Fifty-one patients with moderately advanced PD who could not be satisfactorily controlled with conventional Parkinson’s medication were enrolled in the study at clinical sites in the U.S. Approximately half of the patients received CERE-120, and the other half received sham (placebo) surgery as a control. The patients were monitored for 15 to 24 months to assess the drug’s safety and changes in PD symptoms using multiple endpoints, such as the UPDRS; daily diaries that assessed motor function throughout the day; and the 39-item Parkinson's Disease Questionnaire (PDQ-39), a measure of quality of life.

According to the drug’s developer, CERE-120 is composed of a harmless AAV vector carrying the gene for neurturin, a naturally occurring protein known to repair damaged and dying dopamine-secreting neurons, keeping them alive and restoring function. Neurturin is a member of the same protein family as glial cell-line–derived neurotrophic factor (GDNF). The two molecules have similar pharmacological properties, and both have been shown to benefit the midbrain dopamine neurons that degenerate in PD. Degeneration of these neurons is responsible for the major motor impairments of the disease.

CERE-120 is delivered by stereotactic injection to the terminal fields (i.e., the ends of the degenerating neurons), located in an area of the brain called the putamen, as well as by injection to the cell bodies for these same neurons, located in a different area of the brain, called the substantia nigra.

PD is a progressive movement disorder that affects an estimated 1 million people in the U.S. Its main symptoms — stiffness, tremors, and slowed movements and gait — are caused by a loss of dopamine-containing nerve cells in the substantia nigra. Dopamine is a neurotransmitter involved in controlling movement and coordination. Thus, PD patients exhibit a progressive inability to initiate and control physical movements. No current treatments can reverse the degeneration of these neurons or cure PD.

Source: Ceregene, Inc.; April 19, 2013.

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