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Fox Foundation Awards AC Immune New Grant to Advance Alpha-Synuclein Imaging Agent

Grant award

The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has awarded AC Immune a new grant to further the development of tracer compounds for Parkinson’s disease (PD).

Specifically, this award continues MJFF support for AC Immune’s alpha-synuclein positron-emission tomography (PET) tracer program, aiming for an accurate imaging agent of the alpha-synuclein protein clumps in nerve cells of the brain that are thought to underlie Parkinson’s development and progression.

Positron-emission tomography (PET) is a non-invasive imaging technique that enables the visualization of the metabolic processes in the body. A PET tracer that is alpha-synuclein specific would allow scientists to study the distribution and alterations of these toxic clumps as the disease progresses.

AC Immune researchers has identified several PET tracer compounds with high affinity and selectivity to alpha-synuclein deposits. They did so by screening the company’s library of small molecules for suitable alpha-synuclein PET tracer candidates.

This “molecular collection,” also known as the Morphomer platform, enables the identification of a new class of low molecular weight compounds. This platform, in turn, allows for the generation of small molecules — called morphomers — that specifically bind to misfolded proteins, working to break up the neurotoxic clusters and prevent protein aggregation.

Importantly, these molecules can reach the brains of non-human primates, adding to their potential as a central nervous system tracer.

A lead alpha-synuclein PET tracer candidate, ACI-3024, entered a Phase 1 clinical trial of its ability to capture pathological alpha-synuclein in neurodegenerative diseases like Parkinson’s. The study is assessing the safety, tolerability, and interactions between the body and ACI-3024 (pharmacokinetics and pharmacodynamics) in healthy volunteers.

Jan Stöhr, PhD, head of Non-Alzheimer’s Disease Proteinopathies at AC Immune, will give an oral presentation about this alpha-synuclein PET tracer program at the Fox Foundation’s 13th Annual PD Therapeutics Conference set for Oct. 15 in New York City.

“We are very proud to be working together with MJFF on our a-syn [alpha-synuclein] PET tracer program, which offers patients the potential for earlier diagnosis of PD and facilitates the development … of imaging agents capable of earlier detection and disease monitoring, as well as the development of a broad pipeline of effective therapeutic candidates focused on the prevention and treatment,” Andrea Pfeifer, PhD, CEO of AC Immune, said in a news release.

The Fox Foundation first began supporting AC Immune’s program for alpha-synuclein-specific tracer compounds in 2015. If the program is successful, it could offer a first imaging agent capable of accurately identifying and monitoring Parkinson’s progression.

AC Immune is also working to develop oral small molecule alpha-synuclein inhibitors, and anti-alpha-synuclein antibodies to treat Parkinson’s and related diseases.

The grant amount was not released.

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Imaging Tracer with Potential to Bolster Clinical Trials of Parkinson’s and Its Treatments Favored by EMA

123I-FP-CIT SPECT tracer

The European Medicines Agency (EMA) endorsed an imaging test that can help in identifying Parkinson’ patients with early stage disease but likely to progress quickly — people who might be best suited to taking part in clinical trials.

Development of this clinical assessment tool — which targets disease biomarkers — came through collaborative work involving Critical Path for Parkinson’s (CPP) Consortium, a part of the Critical Path Institute (C-Path), the non-profit group Parkinson’s UK, and several pharmaceutical companies.

“This endorsement from the European Medicines Agency represents many years of hard work and incredible collaboration among companies, universities, and charities facilitated by the Critical Path Institute,” Diane Stephenson, executive director of CPP, who led the effort, said in a press release.

“Through our global project, we’ve been able to bring all the data and expertise together to make a powerful case, so we’re delighted that this endorsement from the EMA will improve the quality and chances of success for future trials of Parkinson’s treatments,” Stephenson added.

The method requires the intravenous injection of a radioactive tracer called 123I-ioflupane, or 123I-FP-CIT, which can be detected by single-photon emission computed tomography (SPECT) imaging. The tracer binds very specifically to dopamine transporter sites on the neurons that are lost to Parkinson’s disease, allowing scientists to detect alterations in dopamine transport — a hallmark event in the disease’s development.

Working as a kind of enrichment biomarker for early stages of Parkinson’s disease, the radioactive tracer helps to differentially diagnose between essential tremor and other parkinsonian disorders, such as progressive supranuclear palsy or multiple system atrophy, and Parkinson’s “subjects with high likelihood of progressing in clinical motor disability.”

The tracer has been available in the European Union since 2000 with the brand name DaTSCANTM, and in the United States since 2011 as DaTscan. In 2015, the U.S. Food and Drug Administration issued a letter of support for the use of this imaging biomarker as a “prognostic biomarker for enrichment in trials for Parkinson’s disease.”

“These brain scans in themselves are not new, but until now there has not been a clear consensus that they can and should be used to select participants for clinical trials,” Stephenson said.

“The use of these brain scans is already being included in new clinical trials at Biogen,” said Michael Ehlers, MD, PhD, executive vice president of research and development at Biogen. “We believe that this new approach will introduce greater efficiency in terms of cost and speed, while ensuring that the right patients are being included in our trials.”

Due to the progressive nature of Parkinson’s, the best approach to slow, stop, or reverse the disease would be by intervening as early as possible. But disease manifestations can be subtle in its early stages, complicating trial recruitment.

Previous reports suggest that up to 15 percent of patients taking part in trials of new Parkinson’s therapies may not be the best candidates to measure potential efficacy, because of scant change in their motor symptoms during the time-limited course of such studies. In its early stages, disease progression can be difficult to predict.

“Being able to rule out individuals who are unlikely to have Parkinson’s could be the difference between a successful trial and failure,” said David Dexter, PhD, a professor at Imperial College London and deputy research director of Parkinson’s UK. “This is a vital step forward in our mission to deliver, as quickly as possible, better treatments, and one day a cure, to people living with Parkinson’s.”

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Source: Parkinson's News Today