PBT434 Prevents Neuron Loss, Improves Motor Function in Animal Model of Neurodegeneration, Prana Reports

Prana Biotechnology’s investigational compound PBT434 prevented neuronal loss and improved motor function in an animal model of multiple system atrophy (MSA), a condition that shares many of Parkinson’s motor symptoms, according to preclinical data.

MSA is a progressive disorder affecting both involuntary functions, such as blood pressure, breathing, and digestion, and motor function, causing slow movement, rigid muscles, and poor balance. The condition is part of a group of atypical Parkinsonian disorders, which exhibit signs and symptoms of Parkinson’s, but normally do not respond well to treatment with levodopa. These disorders are collectively characterized by an abnormal protein buildup within brain cells.

PBT434 is a small molecule designed to inhibit the aggregation of proteins called alpha-synuclein and tau. These protein clumps are hallmarks of Parkinson’s and atypical Parkinsonian disorders.

Prana’s new data show that its treatment candidate prevents the buildup of alpha-synuclein, preserves nerve cells in animals with MSA, and decreases the number of glial cell inclusions (GCIs) in the brain. GCIs are aggregates of alpha-synuclein in glial cells — cells of the central nervous system that provide support and protection to neurons — and are a hallmark of MSA. These benefits were associated with improved motor function.

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The data will be presented at the International Congress of Parkinson’s Disease and Movement Disorders, taking place Oct. 5-9 in Hong Kong.

“Multiple system atrophy, or MSA, is a devastating orphan disease with limited treatment options. These animal data are robust and indicate that PBT434 has excellent potential to help individuals with MSA,” David Stamler, MD, chief medical officer and senior vice president of clinical development at Prana, said in a press release.

Prana started its first human study of PBT434 in June.

“Having recently started our first human study of PBT434, these data represent an important step as we pursue new treatments for Parkinsonian diseases,” Stamler said.

In 2017, Prana sponsored a study in mice showing that PBT434 prevented the loss of dopamine-producing neurons in a region of the brain called the substantia nigra, which is responsible for movement coordination. Degeneration of these neurons is a feature of Parkinson’s disease.

Other benefits included improvement of motor function and restoration of iron levels in the brain, as well as prevention of alpha-synuclein clumping and elimination of the clumps’ toxic effects.

Previous findings suggested that PBT434 may also protect against cognitive and motor dysfunction by preventing metal-mediated degenerative mechanisms.

Prana and Takeda Pharmaceuticals International are also collaborating to test whether PBT434 may improve gastrointestinal damage associated with Parkinson’s.