2019 Annual Report

Highlights
CENTER FOR CANCER & CELL BIOLOGY
The link between taste & neurological disorders
Understanding how the brain processes sweet, bitter and umami tastes may one
day help researchers design more effective drugs for neurological disorders. VAI’s
Dr. Juan Du and Dr. Wei Lü revealed for the first time the near atomic-level structure
of calcium homeostasis modulator 2 (CALHM2), a protein that plays critical roles
in processing taste stimuli and mitigating toxicity in brain cells. CALHM2 works by
sensing chemical and electrical changes in its environment — in the taste buds,
for example — and relaying the information back to the brain. Abnormal changes
in CALHM proteins have been linked to Alzheimer’s disease, stroke and other
neurological conditions; fixing these errors may help create viable treatments in the
future.
CENTER FOR NEURODEGENERATIVE SCIENCE
Collaboration & big data help redefine a rare form of dementia
In a 2019 landmark study, more than 100 scientists from around the world —
including VAI’s Dr. Rita Guerreiro and Dr. José Brás — teamed up to investigate
frontotemporal dementia, a progressive syndrome marked by shrinking of brain
regions that govern behavior and speech. FTD is a rare disease, and FTD caused by
genetic mutations is even rarer, making it especially difficult to study. Often, there
simply aren’t enough cases from which to gather sufficient data. The first-of-its-kind
study in FTD encompassed data from 3,403 individuals, and allowed scientists to
identify patterns that tied specific gene mutations to age of onset, disease duration
and age of death. This is particularly important for people and families with these
mutations, for clinicians managing FTD and for scientists developing precision
medicine approaches and methods for tracking disease progression. Findings in FTD
may also have applications in understanding other types of dementia.
CENTER FOR NEURODEGENERATIVE SCIENCE
Investigating a diabetes drug as a way to slow or stop multiple
system atrophy
Multiple system atrophy is a rare neurodegenerative disease that shuts down
the vital systems in the body, such as the ability to move, to regulate heart rate
and to digest food. In its early stages, it often is mistaken for Parkinson’s disease
and, like Parkinson’s, there is no cure. In 2019, researchers at University College
London began a pilot clinical study to see if the diabetes drug exenatide can slow
or stop progression of MSA. Exenatide has already shown promise as a possible
Parkinson’s treatment because it acts on many of the same biological pathways
affected by neurodegenerative diseases. The trial is supported by Van Andel
Institute, the Defeat MSA Alliance, the John Black Charitable Trust and the MSA
Trust.
CENTER FOR NEURODEGENERATIVE SCIENCE
Unlocking the brain’s secret code
Dr. Viviane Labrie is parsing the human genome and the epigenetic code that
regulates it in search of the root causes of neurological disorders that affect
millions around the globe. In spring 2019, she discovered a mechanism that
accelerates aging in the brain and gives rise to the most devastating features of
Alzheimer’s disease. Later, Labrie and her colleagues found a hot spot of epigenetic
marks that may fuel the psychotic symptoms of schizophrenia and bipolar disorder.
Taken together, her findings are charting new paths toward better diagnostic and
treatment methods for a trio of tough-to-treat diseases.
12 | VAN ANDEL INSTITUTE ANNUAL REPORT 2019