engineering personalized medicine aimbe feb 22 2011

AIMBE

Engineering Personalized Medicine

Michael N. Helmus, Ph.D., Consultant Medical Devices, Biomaterials

Drug Delivery, and Nanotechnology

(508) 767 0585 [email protected]

Feb. 22, 2011

Michael N. Helmus, Ph.D., Consultant [email protected]

Personalized Medicine

'The molecular methods that make personalized medicine

possible include testing for variations in genes, gene

expression, proteins and metabolites, as well as new

treatments that target molecular mechanisms. Test results

are correlated with clinical factors - such as disease state,

prediction of future disease states, drug response, and

treatment prognosis - to help physicians individualize

treatment for each patient'

Personalized Medicine Coalition

www.personalizedmedicinecoalition.org/sci

encepolicy/personalmed-101_overview.php

Personalized Medicine to Drive New Technology Less Invasive Therapies

Custom Implants

Biosensors

Implantable biosensors, eg CHF

Telemetered devices and implants

Molecular Diagnostics

Genomic basis of Disease

Local and Targeted Drug Delivery

Pharmacogenomics

Tissue Engineering

Cell Therapy

New Imaging, eg. Histologic Grade

OCT

Personalized Medicine:

Local and Targeted

Diagnostics and Therapeutics

to allow “individualized

treatment for each patient”


Leverage Potential Disruptive Technologies

Drug Delivery

Therapeutic Polymers

Biodegradables

Tissue Engineering

Stem Cells

Smart Materials

Imaging, e.g. Molecular Imaging

Genomics

Proteomics

Glycomics

Computation

NanoStructures

MEMS

Telemetered/sensored implants


Fu

nct

ion

ali

ty -

Bio

com

pati

bil

ity

Rec

ellu

lari

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on

, an

d n

eogen

esis

of

tiss

ue

Time

Passive Biomaterials

Bioactive, Biodegradables

& Drug Delivery Tissue Engineering

Disruptive Biocompatibility Based Technologies

Genomics Identifying effective Therapies


Interventional Placements

of Implantable Devices and Treatments e.g. CABG, Heart Valves, Joints

Tissue Engineered Constructs, Chordae Tendon

Repair, Biodegradable

Injectables for Heart Failure

Funct

ional

ity

Time

Surgical

Interventional -

Stents MIS

Disruptive Technology: Surgical Procedures

Niche Market: Elderly?

History of Stent Grafts

for AAA

Genomics Identifying Effective

Therapies


Nanopores for drug

delivery

Nanoenabled Diagnostics and Therapies

Nanoparticles to cross The blood brain barrier: Diagnostics, drug delivery

Gold shell nanoparticles for

Tumor ablation

Nanofiber Scaffolds for

Vascular prostheses &

Tissue engineering

Nanodiagnostics for point of care

Diagnosis: infectious disease,

biomarkers

Quantum Dots for Molecular Imaging

Nanoporous filters: Drug delivery, Hemodialysis, Plasmapheresis, Oxygenation – Celgard has been available for 30 + years


Implantation of tissue

engineered construct.

Tissue Engineered Devices

Biopsy/tissue sample for autologous cell

&/or isolation of stem cells.

Culturing of cells to expand if needed.

Scaffolds: Decellularized tissue,

Polymer, Biodegradables,

Bioderived, eg collagen

Seeded scaffolds for

direct implantation or

growth of tissue in

bioreactor

Healed device

http://products.asminternational.org/meddev/viewPicture.aspx?id=487273&now=633645207888125000


Small Molecules

Proteins/Growth Factors

Gene Transfection

Remodeled Organ

In Situ Healing

Injectables to

recruit

bmc’s/tissue

stem cells to

Regenerate in

situ.

Identification of Drivers for New

Technology

• Cost Containment

• New Diagnostics and Point of Care

• Infectious Disease

• Epidemic/Pandemic Surveillance

• Biomarkers for Disease

• Enablement for interventions: e.g.

vulnerable plaque

Personalized

Medicine

Cleveland Clinic announces its top 10 medical

innovations of 2010

1. Molecular imaging biomarker for early detection of Alzheimer's Disease

2. Targeted T-cell antibody for metastatic melanoma

3. First cancer vaccine approved by the FDA

4. Jupiter Study: Statins for healthy individuals

6. Telehealth monitoring for individuals with heart failure

7. Endoscopic weight-loss procedure

8. Exhaled nitric oxide (NO) breath analysis for diagnosing asthma

9. Oral disease modifying treatment for multiple sclerosis

10. Capsule endoscopy for diagnosis of pediatric GI disorders

http://www.cleveland.com/healthfit/index.ssf/2010/11/2010_innovations_summit_clevel.h

tml

• New Therapeutics

– Cancer

– Infectious Disease

– Immune Disease

– Minimally/Less Invasive Procedures

– Implants

– Tissue Engineering

Drivers for New Technology cont.


Commercializing Technology

Pulling Technology across the Valley of Death

Product Commercialization

Discovery &

Research

Development &

Engineering

Manufacturing &

Marketing

“Valley of Death”

Value

•The bridge to commercialization

• Proof of principle in a clinically relevant setting

• Drivers for Development

• Cost Containment, New Therapies, New

Diagnostics and Point of Care Medicine

•Intellectual Property

Commercializing


Recent Examples

Personalized Medicine

* Microfluidics chip can spot rare cancer cells in blood

Mass General Hospital - microfluidics chip to detect groups of rare

tumor cells in a patient's blood sample. The technique could help

improve research into cancer metastasis and spare patients from

undergoing invasive procedures used for collecting tumor samples. MIT

Technology Review (10/5)

*J&J Invests in New Noninvasive Cancer Test

Johnson & Johnson (J&J) has announced that it is investing $30 million

in a new test that could detect—and help doctors treat—a variety of

cancers from a simple blood draw, according to reporting by Yahoo

Canada News. While experts concede that such a test is still years away,

some are predicting that it could revolutionize cancer detection and

treatment.

AdvaMed Smart Briefs

http://ca.news.yahoo.com/j-j-helps-develop-blood-test-spot-1-20110102-211742-558.html


Setting Expectations

How to innovate while addressing concerns.

Suggests need to establish well delineated practice

guidelines as the technology translates into the

clinic

(CNN) – Cancer breakthrough -- or nightmare?

January 11, 2011

“A simple blood test. It's able to detect minute quantities of cancer cells

that might be circulating in your bloodstream.

It's reported to be able to detect a single cell. It's intended to allow

cancer patients to start treatment much earlier.

It's supposed to save lives. It's a cancer breakthrough.

But it's not that simple. The test could just as easily start a cancer

epidemic.”

http://www.cnn.com/2011/HEALTH/01/03/cancer.test/index.html?iref=allsearch

Personalized medicine. Personalized medicine includes the detection of disease

predisposition, screening and early disease diagnosis, prognosis assessment,

pharmacogenomic measurements of drug efficacy and risk of toxic effects, and the

monitoring of the illness until the final disease outcome is known. JS Ross, GS Ginsburg, The Integration of Molecular Diagnostics With Therapeutics

Jeffrey S. Ross, MD, Geoffrey S. Ginsburg, MD, PhD American Journal of Clinical Pathology. 2003;119(1)

http://www.medscape.com/viewarticle/447846

http://www.medscape.com/viewarticle/447846

When its

personal, its

not quick

enough!!!

When it becomes personal!!

Hi Fever, fainting, coughing

ER visit, immediate admission to ICU

Chest X-Ray consistent with bacterial infection

Hi dose Antibiotics

Rapid progression to BiPap and intubation and ventilator

within 4 days with continuing deterioration

Discussion with family

About 4 weeks prior: Exposure to Polyurethane sealant during

renovation, poor ventilation, walls exposed

2 weeks prior: reexposure to Polyurethane sealant

Immediately administered prednisone and antifungal (as precaution)

Lavage indicated no fungal or bacterial involvment

Stopped Antifungal

9 days on ventilator

Diagnosis hypersensitivity pneumonia


Disease Management

Admission

Circulating WBC Biomarkers

Circulating Antibodies

Biosensors

Radiology

Complete blood count

Complete metabolic profile

Blood gases or pulse

oximetry

Bronschoscopy, Bronchoalveolar lavage,

transbronchial biopsy

Thoracoscopic or open-lung biopsy

Radiographically guided transthoracic aspirate

Legionella, Chlamydia, Mycoplasma serology

Fungal serology

Evaluation for congestive heart failure,

pulmonary embolus, neoplasm, connective

tissue disease

Deteriorating patient without definitive

diagnosis of cause

Earlier impetus for lavage and biopsy

Earlier treatment with steroids

Eliminate diagnosis of fungal infection

Eliminate or reduce need for ventilation

More rapid recovery, mitigating DVT

Personalized Medicine Early Disease Diagnosis: Molecular Pathology

Screening

Subclinical Disease processes

Predisposition

Bilateral below knee DVT

Increased heparin, Vena cava filter

Indication of allergic reaction to due to skin hives/rash

Suspicion heparin allergy, change to LMW heparin

Significant bodywide rash

Warfarin therapy

Post release, discovery of hi FVIII disease


Disease Management cont.

Hospital based complications

DVT Increase heparin, Vena Cava Filter

Heparin Allergy LMW Heparin

More severe Heparin Allergy Warfarin

Personalized Medicine Mitigating Complications: Molecular Pathology

Screening Pharmacogenomics

Subclinical Disease processes

Biosensors High FVIII disease

Identification of Heparin allergy

Earlier Warfarin administration

Pharmacogenetics Titrate Warfarin dose

When can Warfarin dose be

eliminated

Micromechanical Sensing & Detection

Nanotechnology Approaches to Sensing and Detection

Dr. James S. Murday Dr. Richard J. Colton, Naval Research Laboratory

http://www.frtr.gov/pdf/meetings/dec04/murday_12-04.pdf

C nanotube networks: Detection via field-

induced polarization of adsorbates on

SWNT surface

BioFETs: thin for efficient sensing (~2 nm).

source drain; specific attachment of DNA or protein

Biosensors Will Drive Personalized Medicine


INSTRUMENTATION/PACKAGING

• Spectrometry

• Light Scattering

• Microfluidics

• Nanosensors

• Biochips

• Thin film transistor arrays

• Scattering techniques

• Tissue culture techniques

MODELING

• Computational modeling:

- biomolecules

- crystallographic structures

- biokinetics and dosimetry

• Tissue-light interactions modeling

APPLICATIONS

• Disease Biomarkers

• DNA/Gene expression

• Chemical and Biotoxin Exposure

• Pathogen sensing

• Molecule detection

• Single molecule detection

Biosensor Development

Modified from:

http://www.ornl.gov/sci/biosensors/abstg_orgchart.pdf#search=%22Advanced%20Biomedical%20Scie

nce%20and%20Technology%20Group%22

Personalized Medicine to Drive New Technology

Local and Targeted

Diagnostics and Therapeutics

to allow “individualized

treatment for each patient”

Drug Delivery,

Tissue Engineering

& Cell Therapy

Biomarker &

Disease

Detection

Less Invasive

Procedures

Michael N. Helmus, Ph.D., Consultant Medical Devices, Biomaterials

Drug Delivery, and Nanotechnology

(508) 767 0585

engineering personalized medicine aimbe feb 22 2011

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