The Development of Drug Therapies for Frontotemporal Dementia Caused by Progranulin Mutations
Pp. 231-291 (61)
Louis De Muynck and Philip Van Damme
In this chapter, we discuss the development of therapies for frontotemporal
dementia caused by progranulin mutations. Although this is a relatively rare and very
specific form of neurodegeneration, the upstream disease cause, being
haploinsufficiency of the growth factor progranulin, offers straightforward opportunities
for therapy development. Substitution of the progranulin deficiency is likely to
counteract the detrimental effects of progranulin haploinsufficiency in patients with
frontotemporal dementia and may prevent the manifestation of the disease in
presymptomatic mutation carriers. As progranulin has neurotrophic and antiinflammatory
properties, therapeutic interventions aimed at augmenting progranulin
levels may also become useful in other forms of neurodegeneration.
Amyotrophic lateral sclerosis, C9orf72, drug development,
frontotemporal dementia, frontotemporal lobar degeneration, granulin,
haploinsufficiency, HDAC inhibitors, motor neuron disease, neuronal ceroid
lipofuscinosis, primary progressive aphasia, progranulin, TMEM106B.
KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND) - VIB, Vesalius Research Center, Laboratory of Neurobiology, Leuven, Belgium - University Hospitals Leuven, Department of Neurology, Leuven, Belgium.