Wearable HATH-1 Auditory Therapy:

Total Hearing Effect?Michael DeSalvio, John Chi, Michael Nguyen, Kevin Ip,

Khine Win

WHAT: THE?

John Chi – Electrical Engineer: System architecture, Software design

Michael J. DeSalvio - Molecular Biologist: Interface design, Biocompatibility

Kevin Ip - Molecular Biologist, Regulatory Contact

Mike Nguyen – Molecular Biologist and Lab Specialist: Drug delivery design, GLP contact

Khine Win – Material Science and Engineering: Fluid transport design, process fabrication

We are not researchers, we are designers!

Problem

Most hearing loss is caused by damaged cochlear hair cells, which do not regenerate

Hearing loss now affects 1 in 5 American teenagers (JAMA, 8-17-2010)

15% of adults between 20-69, 26 million adults, suffer from noise-induced hearing loss (NIHL, National Institute on Deafness and Other Communication Disorders)

25-40% of 60+ in US is hearing impaired - worsening (Yueh et al, 2003)

Current Solutions

Cochlear Implant Hearing Aids Underlying cause

not addressed (hair cell destruction)

Cochlear Implant

• FDA approved in 1984• Approximately $40,000 for procedure• As of 2009, 188,000 worldwide received implants. (Davis, J

2009 Peoria Journal)• Cochlear Implants rely on electrical connections to

auditory nerve, destroying existing structures in the ear• Infection, physical damage to unit, wear and tear

(permanent)• Developed by Cochlear Limited Australia, Advanced

Bionics, Cochlear Corporation, Med-El, etc.

Hearing Aid

Removable prosthetic Many different shapes and sizes $150 to $5,000 Many different manufacturers and designs No surgery Can be bulky and cumbersome Need constant adjustment (feedback, loud noises)

HATH-1 Therapy

Math1 allows transdifferentiation of cochlear cells into functioning auditory hair cells

These transgenic cells shown to be stable and growing after 10 weeks with significant restoration of auditory function (2003, Izumikawa)

Need multiple injection sites Need to distribute throughout cochlea using

micropump to optimize hair cell regeneration densit

HATH-1 Effectiveness

Routes of Entry

Two routes of entry into ear Systemic Route: drug circulates through blood

stream Local Application to inner ear (targeted drug

delivery)

www.gizmowatch.com

Device

Microfluidic circulating pump delivers drug safely to delicate cochlear region

Intracochlear drug delivery device to deliver chemotherapy

Built-in Piezoelectric ABR testing

Extracochlear stimulation maintains auditory regions in brain

FDA Class 2 Device and Class 2 Software

Prototype (Animal model)

Advantages

Does not destroy vestibular structure Temporary prosthetic surgical solution Permanent hearing restoration No need for post-treatment prosthetic Monitored treatment developmet Maintenance is almost identical to existing

cochlear implant

Disadvantages

• Suppress vestibular (balance) system function—with sometimes only minor effects on hearing.

• Risk of developing meningitis• General risk of infection• Cost: $45,000- $150,000 total cost

Where and When

Business location local to Southern California Group competencies allow most development

to take place in-house Approximately 3 years to market with drug

delivery device Milestone 1 – Develop prototype Milestone 2 – 510K Registration with FDA Milestone 3 – Commence clinical trials Milestone 4 – Complete clinical trials

How does it work?

• Delivering Hath 1 transcription factor and other drugs

• Microfluidic pump system with inlet and outlet tubule for delivery

• Use of intracochlear imaging system to monitor distribution of delivered substances

• Use of Extracochlear stimulation during recovery period

• 10 week treatment course

Khine Figure: Prototype (Human Model)

How is it Different?• Does not remove vestibular hair cells

http://www.surgeryencyclopedia.com/Ce-Fi/Cochlear-Implants.html

• Can monitor hair cell growth through non-invasive ABR testing

• Higher distribution of delivered substances compared to delivery

through RWM

• Extracochlear stimulation does not destroy cochlea as opposed to

intracochlear device

Cochlear Anatomy Contains two & three

quarter turns (Basal, Middle & Apex)

3 fluid filled spaces located in parallel

scala vestibuli, tympani & cochlea duct

Fluid contains ionic compositions of Na+, K+, Ca2+ & Cl- (Endolymph & Perilymph)

Surgery

Surgery Opening in the basal turn is

made Carbide micro drills modified

fitted with insertion stops Medical grade adhesive &

dental cement are used Almost identical to already

used implant surgery

System Overview

Extracochlear Stimulator

• Can re-stimulate portions of the brain responsible for hearing even after prolonged “atrophy.” Documented patient Baron Jack Ashley, UK House of Lords

• Can improve hearing after complete deafness

• Reliable and efficient, long life cycle

• Restore hearing without damaging structures in ear canal

Michael N

Fluid Transport System (overview)

Microfluidic pump

Inlet tubule +

precision thermal flow sensor

Reservoir(contains Artificial

perilymph solution)

outlet tubule +

precision thermal flow sensor

Ear

Microcontroller

Fluid Transport (Materials)

Polyetheretherketone (PEEK) tube Biocompatible Excellent mechanical and thermal

resistance Good for application require

vacuum environment ISO 10993 standard & fully USP

Class VI, FDA, NSF and European Pharmacopoeia criteria

Fluid Transport (Materials)

Polyetheretherketone (PEEK) tube Biocompatible Excellent mechanical and thermal

resistance Good for application require vacuum

environment ISO 10993 standard & fully USP Class

VI, FDA, NSF and European Pharmacopoeia criteria

Fluid Transport

Precision thermal sensor Utilizing temperature shift caused by fluid flow Relationship between temp and volume of fluid

flow Microfluidic pump Nano Liter application Zero net transfer Continuous inflow and outflow (not reciprocating

QFD – Power Subsystem

QFD – Power Subsystem

QFD - Battery

Input

Tubing Materials Microprocessors Casing Materials Drug Sensors Circuitry Pumps Software and updates

Change Over Time

Wearing of pumps Degradation of

tubing Degradation of drug Circuitry corrosion Loosening of

delivery template

Degradation/loosening of seals

Degradation of battery Wear on moving parts Degradation of

synthetic endolymph Bodily immune

response

Noise External heat/cold Water/humidity Leaking User opens device Device falls off Blunt force trauma Bubbles in fluid line Flow regulation

failure

Electromagnetic interference

Intracochlear tissue Internal heating Battery failure, leaking Charging mechanism seizes Particulates in fluid line Software bugs Overheating Accumulation of biofilm

Control Factors Water tight seals Flow rate sensors Heat sensors Pressure sensors Electromagnetic

shielding Ultrasonic

agitator for fluid lines, bubble trap

Redundant systems (firmware, tubing, pumps)

Sealed battery compartment

Accessible internal components for servicing

Use biologically inert materials

Consistent software reviews

Reversible flow – self backflushing

Simulation environments

Error States

Cooked/frozen drug Short circuit Clogged pump

mechanism Premature emptying

of drug reservoir Seizure of motor Cracked casing

Water infiltrates system

Infection Memory/firmware

failure Device fails to

charge

Ideal Function

Correct dosage Distribution of drug Motors powered correctly Body accepts implant No leakage ABR measurement of intracochlear cell restoration Healthy cochlea, restored hearing

Summary

Site specific target allows for precise calculation of dosage

Targeted drug delivery which mitigates drug exposure to other tissues (HATH-1 effects in body)

Can be used for middle ear cancers and tumorsCan be used in conjunction with surgery to deliver

antibiotics No additional equipment or maintenance once

treatment is complete

Questions?