Cantabio’s Therapy Candidate Targeting DJ-1 Protein Shows Potential in Parkinson’s Mouse Model

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by Alice Melão |

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Cantabio preclinical results

Cantabio Pharmaceuticals’ small molecule therapeutic candidate was able to protect dopamine-producing brain cells from death and prevent the loss of dopamine in a mouse model of Parkinson’s disease, according to preclinical data.

The compound targets DJ-1, a protein whose loss is associated with the onset of several diseases, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis (ALS).

“The results provide substantial validation of our in-house DJ-1 drug discovery platform’s ability to generate lead drug candidates and for our DJ-1 targeting therapeutic program’s potential for becoming a disease modifying therapeutic for Parkinson’s and Alzheimer’s disease,” Gergely Toth, PhD, CEO and founder of Cantabio, said in a press release.

DJ-1 has been considered an important biomarker of Parkinson’s because mutations in its coding gene, PARK7, have been linked to the familial form of the disease.

Little is known about the biology of this protein and its potential as a therapeutic target. However, some studies suggest that by targeting DJ-1, cells may be protected from oxidative stress — an imbalance in the body’s capacity to clear toxic chemical compounds produced by cells — and protein misfolding.

Cantabio has selected several small molecule chaperones that can specifically bind to the DJ-1 protein in a manner that supports its structural integrity and function, while protecting it from damage.

The therapeutic candidates identified in the company’s CB101 program have shown an ability to protect brain nerve cells from oxidative stress and protein aggregation toxicity. When administered orally, these compounds were able to protect dopaminergic neurons from death and prevent dopamine loss in a mouse model of Parkinson’s disease.

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“[The] drug candidate provided remarkable protection from the neurodegeneration of dopaminergic neurons, which is a critical hallmark of Parkinson’s disease,” Toth said. “These results provide us confidence in the further development of this drug candidate, and we are in the process of testing it in additional disease models of Parkinson’s and Alzheimer’s disease in order to advance it toward clinical studies.”

These positive preclinical results will be discussed at the upcoming XXV International Symposium on Medicinal Chemistry, taking place Sept. 2-6 in Ljubljana, Slovenia.

The scientific poster, “Identification Of Novel DJ-1 Targeting Small Molecules With Protective Activity In Cellular And In Vivo Models Of Parkinson’s Disease,” will be presented by Toth.

The company is also exploring the use of engineered DJ-1 proteins as a strategy to overcome the effects of DJ-1 protein loss and enhance its protective effect in the brain.

By fusing a small cell-penetrant molecule to the DJ-1 protein, the engineered compound can cross the blood-brain-barrier — a semipermeable membrane that protects the brain — and directly reach brain cells. This approach has also shown potential to protect cells from damage in animal models of Parkinson’s disease.