Research Group for Paraneoplastic Neurological Syndromes (PNS)
Paraneoplastic syndromes of the nervous system are rare immune-mediated disorders that manifest in individuals with cancer. PNS develops when the immune system's cancer-fighting agents inadvertently attack parts of the brain, spinal cord, peripheral nerves, or muscles, leading to neurodegeneration. Our focus lies on understanding the most prevalent type of PNS: Paraneoplastic Cerebellar Degeneration (PCD).
PCD serves as an autoimmune model for neurodegeneration linked to breast, ovarian, or other gynecological cancers, predominantly affecting women. Onconeuronal Yo autoantibodies, detectable in both serum and cerebrospinal fluid of PCD patients, target cancer cells and Purkinje neurons in the cerebellum. These antibodies contribute to neuronal dysfunction and Purkinje neuron death by interacting with intracellular cerebellar degeneration-related antigens—CDR2 and CDR2Like—expressed ectopically in tumor cells and endogenously in Purkinje neurons.
Advancing Neuroprotective Therapies:
Our primary objective is to pioneer a neuroprotective therapy by delving into the molecular mechanisms that trigger neurodegeneration. The current therapeutic approach involves tumor removal to prevent further neuronal damage. However, PCD symptoms often precede cancer diagnosis, and tumors are frequently too small to be localized at that stage, complicating this treatment. Unfortunately, there is currently no other effective treatment available to counteract the induced neurodegeneration.
Over the past years, we've made significant strides in developing two artificial PCD ex-vivo systems. These innovative systems enable us to observe biochemical cascades both before and after the intake of Yo autoantibodies in the specifically targeted Purkinje neurons of the cerebellum. Through these approaches, we aim to gain valuable insights into the intricate processes underlying neurodegeneration, ultimately paving the way for effective and targeted neuroprotective interventions.
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Future Scholars Wanted:
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Recognition
The group was evaluated as “very good” by the Norwegian Research Council in 2011, and was part of the Helse Vest Research Prize in 2012 and the University of Bergen Research Prize in 2013.