MJFF Grants Support AC Immune Work Into Ways to Stop Progression

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by Patricia Inácio, PhD |

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The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has awarded about $1.5 million in grants to AC Immune to support work into small molecules against two proteins that are key players in the neurodegeneration underlying Parkinson’s disease.

The two grants will fund research into molecules able to enter the brain and inhibit the aggregation of alpha-synuclein, a disease hallmark, and that can prevent the activation of a pathway that drives neuroinflammation, called the (NOD)-like receptor protein 3 (NLRP3) inflammasome.

“Our Foundation continues to invest in state-of-the-art research to improve our understanding of a-syn [alpha-synuclein] pathology and neuroinflammation in PD [Parkinson’s disease], with the objective to translate these discoveries into therapeutic strategies for PD,” Marco Baptista, PhD, vice president of research programs at the MJFF, said in a press release. “We are pleased to award these two grants to AC Immune to drive the development of therapies that may slow or stop disease progression.”

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A key feature of Parkinson’s is the accumulation of toxic clumps of misfolded alpha-synuclein protein within dopamine-producing nerve cells, triggering their death. Dopamine is a chemical messenger that allows nerve cells to communicate and, among other functions, helps to regulate movement.

An inhibitor able to enter the brain and prevent the clumping of alpha-synuclein could help to halt disease progression. One MJFF grant will support AC Immune’s early-stage program to develop such molecules.

The other grant will support company research into a small molecule that might treat the disease by blocking the activation of the NLRP3 inflammasome in the brain.

Chronic inflammation is believed to contribute to the loss of dopaminergic neurons, particularly in the substantia nigra, a brain region involved in the control of voluntary movements, and one of the most affected in Parkinson’s disease.

Inflammasomes, a group of immune system proteins, are known to play a key role in the activation of inflammatory responses. Inhibiting the NLRP3 inflammasome was shown to lessen neuroinflammation and improve nerve cell survival in different models of neurodegenerative diseases, including Parkinson’s.

“We are extremely proud to receive these new grants and grateful to the MJFF for their continued support of our efforts to develop novel candidates in PD,” said Andrea Pfeifer, CEO of AC Immune. “A-syn and NLRP3 inflammasome both play a major role in several neurodegenerative diseases representing untapped promising targets for research and development.”

The small molecules are being developed using AC Immune’s proprietary Morphomer platform. This platform allows researchers to create small molecules, called morphomers, that specifically bind to misfolded proteins — such as alpha-synuclein — to break up neurotoxic aggregates and prevent their aggregation and proliferation.

“Our Morphomer technology platform once again demonstrates its potential to deliver brain penetrant small molecule protein aggregation inhibitors and builds on AC Immune’s extensive experience in medicinal chemistry, protein biochemistry, and cell biology related to targeting misfolded and aggregation-prone proteins,” Pfeifer added.