Research into fat metabolism: A first step towards solving neurodegenerative diseases

Research into fat metabolism: A first step towards solving neurodegenerative diseases

Dr. Martin Giera, pharmaceutical chemist and Head of the Metabolomics Group at Leiden University Medical Centre (LUMC), together with dr. Rik van der Kant, neuroscientist at Vrije Universiteit Amsterdam and Alzheimer's Centre Amsterdam UMC, have been awarded a $1.6 million grant from the Chan Zuckerberg Initiative’s (CZI) Neurodegeneration Challenge Network. In collaboration with Priyanka Narayan, neuroscientist at the National Institutes of Health (USA), they will further research on the metabolism of fats in the brain.

Previous research has shown that fats (or lipids) play a major role in various brain diseases. Future drugs that can regulate the metabolism of fats in the brain are expected to have a great chance of stopping or even curing neurodegenerative diseases, such as Alzheimer's and Parkinson's. This research project will contribute towards a better understanding of brain diseases, as well as help accelerate the development of drugs that can repair an impaired fat metabolism. 

Cholesterol accumulation in Alzheimer’s

This new grant follows a $150.000 start-up grant the researchers received 18 months ago. According to project leaders, Giera and Van der Kant: "During the start-up phase, our research groups developed a new way to map fat metabolism in human brain cells. We have shown that certain fats - mainly cholesterol - accumulate in brain cells with specific Alzheimer's disease mutations." Based on these and earlier discoveries, the scientists will initiate a clinical trial of potentially new brain cholesterol-lowering drugs in spring 2023, led by Van der Kant at Amsterdam UMC. 

Follow-up studies in other brain diseases

The larger grant will enable Van der Kant and Giera to test whether fat metabolism is also disrupted in at least six other brain diseases. "You can't just take these cells out of someone's head, which is why we are replicating them. We do that by developing stem cells that can be modified to become identical to brain cells. From those, we can study fat metabolism extensively", Giera explains. “By combining advanced fat (lipid) analysis methods developed at LUMC and stem cell technologies from Amsterdam, it is for the first time possible to study the fat metabolism of these cells.”

Neurodegeneration Challenge Network

Collaboration was an important criteria for this grant. "We are very happy to expand our project with other international experts in this field, such as Priyanka Narayan and others within the Neurodegeneration Challenge Network," van der Kant points out. 

The grant has been awarded to a total of 16 projects with focal points in a variety of neurodegenerative diseases and research methods. These grantees are all part of CZI’s Neurodegeneration Challenge Network, which  brings together experimental researchers from different fields with computational biologists and physicians to better understand the fundamental biology of neurodegenerative diseases.

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