Parkinson’s disease (PD) affects about 1.2 percent of the elderly population, who are 71 years of age or older, worldwide. In the U.S., it is estimated that 60,000 Americans receive a PD diagnosis each year. Males are one and a half times more likely to develop Parkinson’s disease than females are. With the anticipated changes in demographics due to the number of seniors within the population, if no disease-modifying treatment is discovered, The Parkinson’s Foundation Prevalence Project estimates that the number of people who have PD in the U.S. will reach 930,000 by 2020 and 1.2 million by 2030.

New PET Tracer and Parkinson’s Disease

Diagnosing Parkinson’s Disease

Noninvasive imaging techniques provide researchers a way to visualize a patient’s metabolic processes: One technique is performed using the positron emission tomography (PET). This tool can be used to diagnose a variety of conditions, including brain diseases, like Parkinson’s. In addition, the PET scan is used to recognize the mechanisms known to cause the symptoms associated with Parkinson’s disease, to help determine the severity of PD by detecting changes in various regions of the patient’s brain and to evaluate how the patient is responding to the Parkinson’s medication being taken.

Understanding Tracers

When a PET scan is performed, a radioactive compound, which is referred to as a tracer, is injected into the patient’s bloodstream. This material travels to the patient’s brain. A 3D image showing the distribution of the tracer within the various areas of the brain is generated. These images are interpreted and the pathology of the patient is determined. There are several tracers used during PET scans. The tracer used helps the physician gain specific information about the disease. These tracers functionally dissect the various aspects of PD.

The 14th International Conference on Alzheimer’s and Parkinson’s Diseases: A New Tracer

At the 14^th International Conference on Alzheimer’s and Parkinson’s Diseases as well as other neurological disorders related to these two diseases that was hosted in Lisbon, Portugal, the findings of a new study, Identification and Characterization of Selective and High Affinity Small Molecules for Positron Emission Tomography (PET) Imaging of Pathological Alpha-Synuclein, were presented by the clinical-stage, biopharmaceutical company, AC Immune SA.

Alpha-Synuclein and Parkinson’s Disease

Patients with PD, have clumps of alpha-synuclein built up within their brains. These clumps are called Lewy bodies and they are toxic. These clumps eventually lead to the death of neurons. Other protein aggregates that are known to influence Parkinson’s disease include beta-amyloid and tau protein aggregates, both of which are commonly seen in those with Alzheimer’s disease; however, the exact process of these two aggregates in relation to PD remains a mystery.

Searching the Morphomer Platform

After detecting Lewy bodies, AC Immune SA searched its library of molecules looking for an acceptable PET alpha-synuclein tracer candidate to use. This robust molecular collection (aka Morphomer platform) makes identifying a new compound possible. In turn, this allows morphomers, which are small molecules that are specifically generated to bind with misfolded proteins that form into neurotoxic clusters (e.g., Lewy bodies) and break them up; thus, inhibiting the ability of the protein to form a cluster.

Once researchers found molecules with the ability to prevent the creation of neurotoxic clusters, the molecules were evaluated to determine how well they would survive while inside another living organism as well as their proficiency at penetrating the brain. Using primates (non-human), the researchers identified molecules that could easily enter into the brain, while offering a fast elimination cycle. Both of which are characteristics desired for the peripheral nervous system tracers. In the near future, the PET alpha-synuclein tracer’s clinical trials will begin.

In a press release, Andrea Pfeifer, PhD and CEO of AC Immune SA stated that, “These data show the potential for what may be the first PET tracer for PD, which we are now moving into a Phase 1 trial.” Pfeifer added, “We believe that therapeutic developments coupled with the diagnostic tools needed to properly identify and select patients allow[s] us to follow disease progression and confirm [the] potential efficacy of therapeutic interventions. This will provide critical differentiation for our product candidates and benefits patients with neurodegenerative diseases.”

With support from the Michael J. Fox Foundation for Parkinson’s Research, the search for a PD cure continues: According to the foundation, we are nearing a breakthrough.

 

Sources

1. https://www.parkinson.org/Understanding-Parkinsons/Statistics
2. https://parkinsonsnewstoday.com/positron-emission-tomography-pet/
3. https://www.globenewswire.com/news-release/2019/03/29/1788111/0/en/AC-Immune-Presents-New-Data-on-Alpha-Synuclein-PET-Tracer-at-AD-PD-Conference.html
4. https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd191576
5. https://www.parkinson.ca/michael-j-fox-foundations-big-strides-in-parkinsons-research-we-are-much-closer-to-finding-a-cure/