MJFF, Merck partner on service for biomarker detection in Parkinson’s

Biomarker linked to nerve cell dysfunction, disease progression in patients

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by Andrea Lobo |

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Merck, in collaboration with the Michael J. Fox Foundation for Parkinson’s Research (MJFF), is providing a service to the scientific community to detect low levels of phospho-serine [pS65]-Ub, a biomarker associated with nerve cell dysfunction in people with Parkinson’s disease.

The SMCxPRO platform is an ultrasensitive immunoassay system that can detect extremely low levels of established disease biomarkers. As a result, it can accurately detect small changes in biomarkers associated with Parkinson’s progression, and monitor patients’ response to therapies.

MJFF is supporting the use of the technology through funding from its “Biomarkers to Support Therapeutic Trials Program,” which is designed to aid the development, optimization, and validation of disease biomarkers.

“Ultrasensitive assays allow us to research multiple biomarkers we know play a role in disease progression. These would be valuable to diagnose and stratify patients and for future therapeutic development,” Nicole Polinski, PhD, director of research resources at MJFF,  said in a press release.

“Current known therapies for [Parkinson’s disease] can treat symptoms but do not slow or halt disease progression. We are hopeful this collaboration will contribute to improved quality of life for patients,” Polinksi added.

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Merck says MJFF support is making research possible

Parkinson’s disease is a neurological disorder caused by the progressive dysfunction and death of dopaminergic neurons, the nerve cells responsible for producing dopamine — a neurotransmitter, or a chemical neurons use to communicate. This impairs dopamine signaling in the brain, which ultimately causes the disease’s symptoms.

By the time motor symptoms do become visible, about 60% to 80% of dopaminergic neurons are already lost or dysfunctional. One biomarker of dopaminergic neuron dysfunction is phosphorylated ubiquitin, or pS65-Ub, which is thought to target damaged mitochondria for degradation. Mitochondria are cells’ powerhouses, whose dysfunction is commonly observed in Parkinson’s and other neurological conditions.

Phosphorylation is a chemical alteration that entails the addition of a phosphate group to a protein, in this case, ubiquitin. Serine, an amino acid that serves as a protein building block, plays a critical role in this process, with serine65 being the target site for the phosphorylation event.

Using the SMCxPRO immunoassay technology to assess cell dysfunction represents a significant step forward in developing new treatment options for people fighting [Parkinson’s disease].

The process of ubiquitin phosphorylation, specifically at serine65, is regulated by the functional interplay of PINK1 and parkin proteins. These proteins are essential for maintaining mitochondrial quality control and safeguarding neurons from damage.

However, the detection of pS65-Ub requires extremely sensitive methods. These are now available using the SMCxPRO system, according to the researchers. The Single Molecule Counting (SMC) technology offers the possibility to detect extremely low protein levels, allowing for previously undetectable proteins to now be quantified.

“Using the SMCxPRO immunoassay technology to assess cell dysfunction represents a significant step forward in developing new treatment options for people fighting [Parkinson’s disease],” said Jean-Charles Wirth, head of science & lab solutions at the Life Science business sector of Merck.

“We’re proud to offer our service through support from The Michael J. Fox Foundation to make this research possible,” Wirth added.