Personalized Hearing Devices Translational and Personalized Medicine Initiative

Personalized Hearing Devices Translational and Personalized Medicine Initiative Research Day Oct 8, 2015

Personalized Hearing Devices • Dr. Terry Young, Genetics, Memorial University • Principal Investigator • Dr. Susan Stanton, Hearing Science and Audiology, Western University, Co- PI • Dr. Ian Bruce, Auditory Engineering Laboratory, Mc. Master University, Collaborator • Anne Griffin, Audiologist and Research Associate, Young Lab

Personalized Hearing Devices • HEARING LOSS: – very common – highly genetic condition • To date, more than 100 genes implicated in hearing loss • Most genetic hearing loss caused by single mutation

Personalized Hearing Devices • Young Lab discovery projects over last 12 years: • Founder Population of Newfoundland Labrador • Over 200 probands with hearing loss • Many large multiple-generation pedigrees • Many family members willing to help – motivated by the potential for a better future for people with hearing loss

Personalized Hearing Devices GENE DNA CHANGES TYPE TMPRSS 3 c. 782+3 del. GAG WFS 1 c. 2146 G>A Missense PCDH 15 c. 1583 T>A Point Mutation KCNQ 4 c. 806_808 del. CCT Deletion GJB 2 GJB 6 c. 35 del. G c. del D 13 S 1830 Frameshift c. 782+3 del. GAG Frameshift/SNP c. 101 T>C Large Deletion MTRNR 1 Point Mutation A 1555 G SMPX c. 99 del. C Frameshift COCH c. 208 C>T Missense TECTA C. 2657 A>G Missense GJB 3 c. 94 C>T FOXL 1 c. 976_990 del c. 70 T>A c. 94 C>T Missense Deletion

PERSONALIZED HEARING DEVICES • What translational opportunities are generated by these discoveries? • Hearing aids most common treatment for permanent hearing loss • Major advances in technology with introduction of digital signal processing • Vastly more potential than is currently utilized

Personalized Hearing Devices • The trouble with hearing aids……. - they don’t do enough for HEARING - informed by VERY limited auditory data - there is huge digital capacity BUT No Clear Rationale for how to PERSONALIZE

Personalized Hearing Devices

Personalized Hearing Devices • Good News: Other measurements of auditory function are available! • Cost prohibitive to determine develop detailed auditory profiles through these tests alone • Greatest difficulty: heterogeneity of hearing loss • Need population(s) with homogenous hearing loss • Even Better News: We have homogenous populations!

Personalized Hearing Devices • Phase 1: Infrastructure and proof of concept studies • • Subjects: 3 families: known genetic cause of hearing loss Translational Genomics Hearing Research lab in GFW Deep phenotyping studies Computer modelling of detailed auditory profiles • Phase 2: Industrial partner, new hearing aid algorithms • To address specific functional deficits • Test on family members • Test on other populations for generalization of technology

WFS 1 2005. A 020 Site: GFW Age: 35 yrs TEN 500 750 1000 1500 2000 3000 4000 Unmasked 58 58 54 56 48 28 16 TEN level 70 70 masked 84 82 78 76 74 72 64 TEN 500 750 1000 1500 2000 3000 4000 Unmasked 62 64 58 52 50 34 18 TEN level 70 70 masked 88 86 78 74 70 72 68

Personalized Hearing Devices Many thanks to : all the participating families all our volunteers and supporters Town of Grand Falls-Windsor/ Excite Corporation: Partner and grant proponent. Funding agencies are acknowledged unofficially (pending formal announcement of project)