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Sascha Alles

Postdoctoral Research Fellow

Sascha Alles's picture

Lab Phone Number

604-822-6805

Email Addresses

saschaalles@msl.ubc.ca

Name

Snutch Lab

Building

MSL

Room Number

259

Associated Departments

Djavad Mowafaghian Centre for Brain Health

Professional Profile

PhD, University of Alberta (2016). BSc Hons, Imperial College London (2010).

Canadian Pain Society Award (2012), FoMD UAlberta 75th Anniversary Award (2014), Profiling Alberta’s Graduate Students Award (2015).

Member, Edmonton Pain Interest Group (2012-present); Member, Society for Neuroscience (2015-present); Member, Canadian Association for Neuroscience (2011-present); Member, Canadian Pain Society (2012-present); Member, Pain Society of Alberta (2012-present); Member, Golden Key International Honour Society (2011-present)

Research Area

Migraine is characterized by the recurrence of headache attacks, thought to be triggered by a phenomenon called Spreading Depression (SD). SD is a wave of nerve cell activation followed by inactivity that travels across the brain and believed to underlie migraine aura. Much of our current understanding of migraine comes from studies of familial hemiplegic migraine type-1 (FHM-1), a form of migraine with aura that is caused by mutations in a type of protein called a voltage-gated calcium channel. These channels form pores in the cell membrane of neurons and contribute to the control of electrical excitability in the brain. Our lab is interested in the R192Q (mild form) and S218L (more severe form) human mutations underlying FHM-1. It has been shown that these mutations make neurons ‘hyperexcitable’ and can more readily activate headache mechanisms associated with migraine.

The clinically used gabapentinoid drugs, gabapentin and pregabalin, are poorly understood as they were originally developed to treat epilepsy and have since been adopted to treat chronic neuropathic pain. Recent studies suggest that pregabalin in particular may have potential for treating migraine although how it might affect the underlying migraine mechanisms has not been determined.

In preliminary studies, we have investigated the effects of pregabalin on SD in mice models of FHM-1 that closely mimic the human disease state. We have found that pregabalin indeed exerts specific effects on FHM-1 mutant animals and that these changes are distinct from non-migraine control animals.

To further study the mechanisms of pregabalin effects, we make use of electrophysiological, optogenetic, electroencephalographic, MRI-based as well as state-of-the-art targeted genetic knockdown approaches. This work will provide insights into the potential of pregabalin for treatment in migraineurs as well as the pathophysiological mechanisms of human mutations underlying FHM-1.

Relevant Publications

Cain SM, Bohnet B, LeDue JM, Garcia E, Yung AC, Tyson JR, Alles SR, Han H, van den Maagdenberg AM, Kozlowski P, MacVicar BA and Snutch TP. (2017) In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures. Proceedings of the National Academy of Sciences. Published ahead of print February 21, 2017. DOI:10.1073/pnas.1614447114.

Adams PJ, Rungta RL, Garcia E, van den Maagdenberg AM, MacVicar BA and Snutch TP. (2010) Contribution of calcium-dependent facilitation to synaptic plasticity revealed by migraine mutations in the P/Q-type calcium channel. Proceedings of the National Academy of Sciences 26;107:18694–9. DOI: 10.1073/pnas.1009500107

Alles SR and Smith PA. (2016) The Anti-Allodynic Gabapentinoids: Myths, Paradoxes and Acute Effects. The Neuroscientist. DOI: 10.1177/1073858416628793.