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Page 10 of 24 Neuroimmunol Neuroinflammation 2019;6:15 I http://dx.doi.org/10.20517/2347-8659.2019.019

13. Ketogenic diets in parkinson’s and alzheimer’s

Matthew C. L. Phillips, Deborah K. J. Murtagh, Linda J. Gilbertson, Fredrik J. S. Asztely,
Christopher D. P. Lynch

Department of Neurology, Waikato Hospital, Hamilton 3204, New Zealand

Aging is accompanied by a mild decline in bioenergetic capacity on many structural levels (molecule,
organelle, and cell) in cells throughout the body. In neurons afflicted by Parkinson’s (PD) and Alzheimer’s
(AD), this decline is pathologically accelerated. Given that they alter multi-targeted nutrient sensors,
metabolic therapies such as calorie restriction, intermittent fasting, and high-fat, low-carbohydrate
ketogenic diets may be able to restore the bioenergetic decline at all these structural levels; ketogenic
diets are probably the most sustainable of these options in PD and AD. In 2017, we developed a protocol
to support 47 people with PD randomized to either a low-fat or ketogenic diet for 8 weeks. Primary
outcomes were between-group changes in motor and nonmotor scores from baseline to week 8. By the
end of the study, the ketogenic group showed clinically and significantly greater nonmotor score baseline
improvements (41% compared to 11%), particularly in urinary problems, pain, fatigue, daytime sleepiness,
and cognitive impairment. In mid-2019, Waikato Hospital will coordinate a similar randomized controlled
study in patients with mild AD. Primary outcomes will be between-group changes in cognition, function,
and quality of life scores from baseline to week 12.

14. Pharmacological annotation of polygenic risk in individuals with psychiatric disorders

Murray J. Cairns, William Reay

School of Biomedical Sciences and Pharmacy, The University of Newcastle, NSW, Australia

With high rates of heritability, the genetic analysis of psychiatric disorders is seen as an important
strategy to identify the molecular determinants of its pathogenesis and therefore more specific targets for
therapeutic intervention. In many respects, large genome wide association studies have delivered on this
expectation, by revealing hundreds of genomic loci. Several significant challenges, however, remain to
be overcome before we can more effectively capitalize on these discoveries, as most of the known genetic
risk is complex and involves hundreds of genes. Where risk loci can be mapped to individual genes, their
small effect size and/or low frequency may, by themselves, not present a compelling case for therapeutic
development. To address this challenge, we are investigating an approach that exploits systems biology to
aggregate genetic burden of complex traits into clinically actionable pathways. We have been exploring
this concept with both SNP array and whole genome sequencing data for individual participants in the
Australian Schizophrenia Research Bank cohort and identify several existing compounds that could
potentially be directed with more biological specificity to patients with higher levels of risk in associated
pathways. While some of these drugs have been used in schizophrenia, or are under investigation for use
in the disorder, many are approved for use in other conditions and have not been considered in the context
of psychiatric treatment. This approach has the potential to provide mechanism for precision treatment of
schizophrenia and other psychiatric disorders, particularly in difficult treatment resistant cases.