Considering a new

approach to treating

Diabetic neuropathy

DISCLOSURES

Bruce Werber DPM FACFAS

Founder and Past President of Amnio Technology 2012-2015

Past President StimStep wireless 2016

Current CEO Anu Life Sciences

Patents

orthopedic plate and screw system 8529608 ndash Terrill et al 2012

acellular placental tissue processing United States Patent 9132156 ndash Werber et al 2015

7 pending patents related to placental tissue 1 pending related to orthopedic biologic implant

Financial relationships

Biotech Products Services and Research (BPSR ndash OTC) COO

Anu LifeSciences llcCEO

AniCell Biotechnologies llc investor and consultantld) amniotic allografts for Animals

There is a single light of science and to brighten it

anywhere is to brighten it everywhere

Isaac Asimov

THE CHALLENGE NON-HEALING WOUNDS AND PAIN

The Problem Diabetic Peripheral Neuropathy66 Type 1 diabetics59 Type 2 diabetics

Non PainfulNot aware

of its

presence

increased

risk of

wounds

Affect almost 50

Of Patients with type

1 and 2

29 Mil people in USA

with Diabetes

90 unaware that they

Have neuropathy

WHO predicts44 of

population by

2030

171 mil in 2000

366 mil in 2030

60-70 have

neuropathy

Painful taking

meds with variety

of adverse events

d

i

a

b

e

ti

c

The Neuropathic ConsequencesMore than 50 develop infected wounds

20 go on to amputationContralateral leg gt50 risk of amputation

5 year mortality after amputation is 68

DSPN cost USA 245Billion year

DFU cost 100k minimum per episode

The Maze of Causation Theories

Dellon et al

fibro-osseous compression sites nerve enlargement and entrapment as diabetic metabolic disease developed

Shimizu et al

Increase type IV collagen and Fibronectin production due to glycation end products Basement

membrane becomes thicker

Dyck et alcompression of the affected No evidence of axonal degeneration

LEEDiabetic nerve enlargement has been demonstrated

ObrosovaCannot replenish free radical scavengers causing slow down of the ATP energy production

Double Crush

Syndrome

Mechanical stiffening of connective tissue affecting

pericytes

Swelling within from extracellular

fluid

Evidence increased diameter on US studies

C-fibers affected

early stages

Authors confirmatory studies ndash Rosenbloom-silverstein 25-26 Tesafye 26

Zhang Lee 242728 Upton-Mccomas 29 Dellon 30

Neuropathic pain is very often refractory to

phamacotherapies along with considerable

unwanted side effects

THE DOWNSIDE OF PHARMACOTHERPYNeuropathic pain is very often refractory to

pharmacotherapies greater than 30 to 50 40 unable to achieve any level of pain relief

along with considerable unwanted side

effects

Remember

Pharmaceuticals are toxins with beneficial

side effects

long-term use of these conventional medications

may lead to significant side effects as well as

abuse 42 4344

pharmaceuticals = high cost to the health system

patients that fail these therapies - suffer

pain and wounds 45

Pharmaceuticals are toxins with beneficial side effects

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

DISCLOSURES

Bruce Werber DPM FACFAS

Founder and Past President of Amnio Technology 2012-2015

Past President StimStep wireless 2016

Current CEO Anu Life Sciences

Patents

orthopedic plate and screw system 8529608 ndash Terrill et al 2012

acellular placental tissue processing United States Patent 9132156 ndash Werber et al 2015

7 pending patents related to placental tissue 1 pending related to orthopedic biologic implant

Financial relationships

Biotech Products Services and Research (BPSR ndash OTC) COO

Anu LifeSciences llcCEO

AniCell Biotechnologies llc investor and consultantld) amniotic allografts for Animals

There is a single light of science and to brighten it

anywhere is to brighten it everywhere

Isaac Asimov

THE CHALLENGE NON-HEALING WOUNDS AND PAIN

The Problem Diabetic Peripheral Neuropathy66 Type 1 diabetics59 Type 2 diabetics

Non PainfulNot aware

of its

presence

increased

risk of

wounds

Affect almost 50

Of Patients with type

1 and 2

29 Mil people in USA

with Diabetes

90 unaware that they

Have neuropathy

WHO predicts44 of

population by

2030

171 mil in 2000

366 mil in 2030

60-70 have

neuropathy

Painful taking

meds with variety

of adverse events

d

i

a

b

e

ti

c

The Neuropathic ConsequencesMore than 50 develop infected wounds

20 go on to amputationContralateral leg gt50 risk of amputation

5 year mortality after amputation is 68

DSPN cost USA 245Billion year

DFU cost 100k minimum per episode

The Maze of Causation Theories

Dellon et al

fibro-osseous compression sites nerve enlargement and entrapment as diabetic metabolic disease developed

Shimizu et al

Increase type IV collagen and Fibronectin production due to glycation end products Basement

membrane becomes thicker

Dyck et alcompression of the affected No evidence of axonal degeneration

LEEDiabetic nerve enlargement has been demonstrated

ObrosovaCannot replenish free radical scavengers causing slow down of the ATP energy production

Double Crush

Syndrome

Mechanical stiffening of connective tissue affecting

pericytes

Swelling within from extracellular

fluid

Evidence increased diameter on US studies

C-fibers affected

early stages

Authors confirmatory studies ndash Rosenbloom-silverstein 25-26 Tesafye 26

Zhang Lee 242728 Upton-Mccomas 29 Dellon 30

Neuropathic pain is very often refractory to

phamacotherapies along with considerable

unwanted side effects

THE DOWNSIDE OF PHARMACOTHERPYNeuropathic pain is very often refractory to

pharmacotherapies greater than 30 to 50 40 unable to achieve any level of pain relief

along with considerable unwanted side

effects

Remember

Pharmaceuticals are toxins with beneficial

side effects

long-term use of these conventional medications

may lead to significant side effects as well as

abuse 42 4344

pharmaceuticals = high cost to the health system

patients that fail these therapies - suffer

pain and wounds 45

Pharmaceuticals are toxins with beneficial side effects

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

THE CHALLENGE NON-HEALING WOUNDS AND PAIN

The Problem Diabetic Peripheral Neuropathy66 Type 1 diabetics59 Type 2 diabetics

Non PainfulNot aware

of its

presence

increased

risk of

wounds

Affect almost 50

Of Patients with type

1 and 2

29 Mil people in USA

with Diabetes

90 unaware that they

Have neuropathy

WHO predicts44 of

population by

2030

171 mil in 2000

366 mil in 2030

60-70 have

neuropathy

Painful taking

meds with variety

of adverse events

d

i

a

b

e

ti

c

The Neuropathic ConsequencesMore than 50 develop infected wounds

20 go on to amputationContralateral leg gt50 risk of amputation

5 year mortality after amputation is 68

DSPN cost USA 245Billion year

DFU cost 100k minimum per episode

The Maze of Causation Theories

Dellon et al

fibro-osseous compression sites nerve enlargement and entrapment as diabetic metabolic disease developed

Shimizu et al

Increase type IV collagen and Fibronectin production due to glycation end products Basement

membrane becomes thicker

Dyck et alcompression of the affected No evidence of axonal degeneration

LEEDiabetic nerve enlargement has been demonstrated

ObrosovaCannot replenish free radical scavengers causing slow down of the ATP energy production

Double Crush

Syndrome

Mechanical stiffening of connective tissue affecting

pericytes

Swelling within from extracellular

fluid

Evidence increased diameter on US studies

C-fibers affected

early stages

Authors confirmatory studies ndash Rosenbloom-silverstein 25-26 Tesafye 26

Zhang Lee 242728 Upton-Mccomas 29 Dellon 30

Neuropathic pain is very often refractory to

phamacotherapies along with considerable

unwanted side effects

THE DOWNSIDE OF PHARMACOTHERPYNeuropathic pain is very often refractory to

pharmacotherapies greater than 30 to 50 40 unable to achieve any level of pain relief

along with considerable unwanted side

effects

Remember

Pharmaceuticals are toxins with beneficial

side effects

long-term use of these conventional medications

may lead to significant side effects as well as

abuse 42 4344

pharmaceuticals = high cost to the health system

patients that fail these therapies - suffer

pain and wounds 45

Pharmaceuticals are toxins with beneficial side effects

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

The Problem Diabetic Peripheral Neuropathy66 Type 1 diabetics59 Type 2 diabetics

Non PainfulNot aware

of its

presence

increased

risk of

wounds

Affect almost 50

Of Patients with type

1 and 2

29 Mil people in USA

with Diabetes

90 unaware that they

Have neuropathy

WHO predicts44 of

population by

2030

171 mil in 2000

366 mil in 2030

60-70 have

neuropathy

Painful taking

meds with variety

of adverse events

d

i

a

b

e

ti

c

The Neuropathic ConsequencesMore than 50 develop infected wounds

20 go on to amputationContralateral leg gt50 risk of amputation

5 year mortality after amputation is 68

DSPN cost USA 245Billion year

DFU cost 100k minimum per episode

The Maze of Causation Theories

Dellon et al

fibro-osseous compression sites nerve enlargement and entrapment as diabetic metabolic disease developed

Shimizu et al

Increase type IV collagen and Fibronectin production due to glycation end products Basement

membrane becomes thicker

Dyck et alcompression of the affected No evidence of axonal degeneration

LEEDiabetic nerve enlargement has been demonstrated

ObrosovaCannot replenish free radical scavengers causing slow down of the ATP energy production

Double Crush

Syndrome

Mechanical stiffening of connective tissue affecting

pericytes

Swelling within from extracellular

fluid

Evidence increased diameter on US studies

C-fibers affected

early stages

Authors confirmatory studies ndash Rosenbloom-silverstein 25-26 Tesafye 26

Zhang Lee 242728 Upton-Mccomas 29 Dellon 30

Neuropathic pain is very often refractory to

phamacotherapies along with considerable

unwanted side effects

THE DOWNSIDE OF PHARMACOTHERPYNeuropathic pain is very often refractory to

pharmacotherapies greater than 30 to 50 40 unable to achieve any level of pain relief

along with considerable unwanted side

effects

Remember

Pharmaceuticals are toxins with beneficial

side effects

long-term use of these conventional medications

may lead to significant side effects as well as

abuse 42 4344

pharmaceuticals = high cost to the health system

patients that fail these therapies - suffer

pain and wounds 45

Pharmaceuticals are toxins with beneficial side effects

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

The Neuropathic ConsequencesMore than 50 develop infected wounds

20 go on to amputationContralateral leg gt50 risk of amputation

5 year mortality after amputation is 68

DSPN cost USA 245Billion year

DFU cost 100k minimum per episode

The Maze of Causation Theories

Dellon et al

fibro-osseous compression sites nerve enlargement and entrapment as diabetic metabolic disease developed

Shimizu et al

Increase type IV collagen and Fibronectin production due to glycation end products Basement

membrane becomes thicker

Dyck et alcompression of the affected No evidence of axonal degeneration

LEEDiabetic nerve enlargement has been demonstrated

ObrosovaCannot replenish free radical scavengers causing slow down of the ATP energy production

Double Crush

Syndrome

Mechanical stiffening of connective tissue affecting

pericytes

Swelling within from extracellular

fluid

Evidence increased diameter on US studies

C-fibers affected

early stages

Authors confirmatory studies ndash Rosenbloom-silverstein 25-26 Tesafye 26

Zhang Lee 242728 Upton-Mccomas 29 Dellon 30

Neuropathic pain is very often refractory to

phamacotherapies along with considerable

unwanted side effects

THE DOWNSIDE OF PHARMACOTHERPYNeuropathic pain is very often refractory to

pharmacotherapies greater than 30 to 50 40 unable to achieve any level of pain relief

along with considerable unwanted side

effects

Remember

Pharmaceuticals are toxins with beneficial

side effects

long-term use of these conventional medications

may lead to significant side effects as well as

abuse 42 4344

pharmaceuticals = high cost to the health system

patients that fail these therapies - suffer

pain and wounds 45

Pharmaceuticals are toxins with beneficial side effects

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

The Maze of Causation Theories

Dellon et al

fibro-osseous compression sites nerve enlargement and entrapment as diabetic metabolic disease developed

Shimizu et al

Increase type IV collagen and Fibronectin production due to glycation end products Basement

membrane becomes thicker

Dyck et alcompression of the affected No evidence of axonal degeneration

LEEDiabetic nerve enlargement has been demonstrated

ObrosovaCannot replenish free radical scavengers causing slow down of the ATP energy production

Double Crush

Syndrome

Mechanical stiffening of connective tissue affecting

pericytes

Swelling within from extracellular

fluid

Evidence increased diameter on US studies

C-fibers affected

early stages

Authors confirmatory studies ndash Rosenbloom-silverstein 25-26 Tesafye 26

Zhang Lee 242728 Upton-Mccomas 29 Dellon 30

Neuropathic pain is very often refractory to

phamacotherapies along with considerable

unwanted side effects

THE DOWNSIDE OF PHARMACOTHERPYNeuropathic pain is very often refractory to

pharmacotherapies greater than 30 to 50 40 unable to achieve any level of pain relief

along with considerable unwanted side

effects

Remember

Pharmaceuticals are toxins with beneficial

side effects

long-term use of these conventional medications

may lead to significant side effects as well as

abuse 42 4344

pharmaceuticals = high cost to the health system

patients that fail these therapies - suffer

pain and wounds 45

Pharmaceuticals are toxins with beneficial side effects

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

Double Crush

Syndrome

Mechanical stiffening of connective tissue affecting

pericytes

Swelling within from extracellular

fluid

Evidence increased diameter on US studies

C-fibers affected

early stages

Authors confirmatory studies ndash Rosenbloom-silverstein 25-26 Tesafye 26

Zhang Lee 242728 Upton-Mccomas 29 Dellon 30

Neuropathic pain is very often refractory to

phamacotherapies along with considerable

unwanted side effects

THE DOWNSIDE OF PHARMACOTHERPYNeuropathic pain is very often refractory to

pharmacotherapies greater than 30 to 50 40 unable to achieve any level of pain relief

along with considerable unwanted side

effects

Remember

Pharmaceuticals are toxins with beneficial

side effects

long-term use of these conventional medications

may lead to significant side effects as well as

abuse 42 4344

pharmaceuticals = high cost to the health system

patients that fail these therapies - suffer

pain and wounds 45

Pharmaceuticals are toxins with beneficial side effects

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

Neuropathic pain is very often refractory to

phamacotherapies along with considerable

unwanted side effects

THE DOWNSIDE OF PHARMACOTHERPYNeuropathic pain is very often refractory to

pharmacotherapies greater than 30 to 50 40 unable to achieve any level of pain relief

along with considerable unwanted side

effects

Remember

Pharmaceuticals are toxins with beneficial

side effects

long-term use of these conventional medications

may lead to significant side effects as well as

abuse 42 4344

pharmaceuticals = high cost to the health system

patients that fail these therapies - suffer

pain and wounds 45

Pharmaceuticals are toxins with beneficial side effects

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

THE DOWNSIDE OF PHARMACOTHERPYNeuropathic pain is very often refractory to

pharmacotherapies greater than 30 to 50 40 unable to achieve any level of pain relief

along with considerable unwanted side

effects

Remember

Pharmaceuticals are toxins with beneficial

side effects

long-term use of these conventional medications

may lead to significant side effects as well as

abuse 42 4344

pharmaceuticals = high cost to the health system

patients that fail these therapies - suffer

pain and wounds 45

Pharmaceuticals are toxins with beneficial side effects

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

A NEW PATHWAY to TREATMENT

And

Neuro-Modulation

A New Paradigm

Biologics

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

VAGUS NERVEmdash controls

everything from blood pressure to

sexual arousalmdashto treat inflammation

associated with PTSD

NERVE STIMULATION conveys a signal to

the spleen where the platelets

receive the signal

This signal ldquoprimesrdquo the platelets

prepping them to form clots if they

encounter a wound anywhere in the body

NEURAL TOURNIQUET reduced bleeding time by 40 percent and

volume of blood loss by 50 percent Within three minutes of

jolting the pigrsquos nerve the researchers measured an increase in

an enzyme associated with clotting at the site of injury

A new Treatment alternative for autoimmune disease

PERCUTANEOUS WIRELESS

NEUROMODULATION

W I R E L E S S P A I N R E L I E F T M

Neuromodulation a pathway to

improved control and avoiding the

morbidities of long term medications

Quell device

WE ALREADY USE ELECTRIC BONE

STIMULATION

HOW DOES NEUROMODULATION WORKActively stimulating targeted nerve to produce a natural biological response Frequency 10HZ

Meta analysis by

Thalkral RCT by

Koel

RBecker

Injury site + charge

Flip polarity to ndash

Promote healing

Blastema - Tissue Regeneration ndash Salamanders

Blastema is the point of regeneration of lost parthellip

Reversing the electrical field creating a shift in polarity allows blastema to

growhellip

if Polarity does not shift then there is no healing

Same in a non healing fracture Dr Robert Becker (bone stimulation upstate NY medical center)

PLACENTAL ALLOGRAFT

OPHTHALMIC HEALING

mdash Tandon R Br J Ophthalmol 201195(2)199-204

At

Presentation

Final

VisitAmniotic Membrane

Transplant

Standard Medical

Care

Day 0 ndash 47cm Day 63 ndash Closed Margin

Patient LM - Comparative

22

Pre injection

painful scar

BedriddenFirst in Man Amniotic Stem Cell Injection Promotes Scar Remodeling and

Healing Processes in Late-Stage Fibrosis

Courtney Hemphill Katherine Stavoe Zain Khalpey

PII S0167-5273(14)00682-2

DOI doi 101016jijcard201404023

International Journal of Cardiology

14 days post injection

no pain

normal turgor

walking without pain

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

PERCUTANEOUS WIRELESS

NEUROMODULATION

W I R E L E S S P A I N R E L I E F T M

Neuromodulation a pathway to

improved control and avoiding the

morbidities of long term medications

Quell device

WE ALREADY USE ELECTRIC BONE

STIMULATION

HOW DOES NEUROMODULATION WORKActively stimulating targeted nerve to produce a natural biological response Frequency 10HZ

Meta analysis by

Thalkral RCT by

Koel

RBecker

Injury site + charge

Flip polarity to ndash

Promote healing

Blastema - Tissue Regeneration ndash Salamanders

Blastema is the point of regeneration of lost parthellip

Reversing the electrical field creating a shift in polarity allows blastema to

growhellip

if Polarity does not shift then there is no healing

Same in a non healing fracture Dr Robert Becker (bone stimulation upstate NY medical center)

PLACENTAL ALLOGRAFT

OPHTHALMIC HEALING

mdash Tandon R Br J Ophthalmol 201195(2)199-204

At

Presentation

Final

VisitAmniotic Membrane

Transplant

Standard Medical

Care

Day 0 ndash 47cm Day 63 ndash Closed Margin

Patient LM - Comparative

22

Pre injection

painful scar

BedriddenFirst in Man Amniotic Stem Cell Injection Promotes Scar Remodeling and

Healing Processes in Late-Stage Fibrosis

Courtney Hemphill Katherine Stavoe Zain Khalpey

PII S0167-5273(14)00682-2

DOI doi 101016jijcard201404023

International Journal of Cardiology

14 days post injection

no pain

normal turgor

walking without pain

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

Quell device

WE ALREADY USE ELECTRIC BONE

STIMULATION

HOW DOES NEUROMODULATION WORKActively stimulating targeted nerve to produce a natural biological response Frequency 10HZ

Meta analysis by

Thalkral RCT by

Koel

RBecker

Injury site + charge

Flip polarity to ndash

Promote healing

Blastema - Tissue Regeneration ndash Salamanders

Blastema is the point of regeneration of lost parthellip

Reversing the electrical field creating a shift in polarity allows blastema to

growhellip

if Polarity does not shift then there is no healing

Same in a non healing fracture Dr Robert Becker (bone stimulation upstate NY medical center)

PLACENTAL ALLOGRAFT

OPHTHALMIC HEALING

mdash Tandon R Br J Ophthalmol 201195(2)199-204

At

Presentation

Final

VisitAmniotic Membrane

Transplant

Standard Medical

Care

Day 0 ndash 47cm Day 63 ndash Closed Margin

Patient LM - Comparative

22

Pre injection

painful scar

BedriddenFirst in Man Amniotic Stem Cell Injection Promotes Scar Remodeling and

Healing Processes in Late-Stage Fibrosis

Courtney Hemphill Katherine Stavoe Zain Khalpey

PII S0167-5273(14)00682-2

DOI doi 101016jijcard201404023

International Journal of Cardiology

14 days post injection

no pain

normal turgor

walking without pain

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

WE ALREADY USE ELECTRIC BONE

STIMULATION

HOW DOES NEUROMODULATION WORKActively stimulating targeted nerve to produce a natural biological response Frequency 10HZ

Meta analysis by

Thalkral RCT by

Koel

RBecker

Injury site + charge

Flip polarity to ndash

Promote healing

Blastema - Tissue Regeneration ndash Salamanders

Blastema is the point of regeneration of lost parthellip

Reversing the electrical field creating a shift in polarity allows blastema to

growhellip

if Polarity does not shift then there is no healing

Same in a non healing fracture Dr Robert Becker (bone stimulation upstate NY medical center)

PLACENTAL ALLOGRAFT

OPHTHALMIC HEALING

mdash Tandon R Br J Ophthalmol 201195(2)199-204

At

Presentation

Final

VisitAmniotic Membrane

Transplant

Standard Medical

Care

Day 0 ndash 47cm Day 63 ndash Closed Margin

Patient LM - Comparative

22

Pre injection

painful scar

BedriddenFirst in Man Amniotic Stem Cell Injection Promotes Scar Remodeling and

Healing Processes in Late-Stage Fibrosis

Courtney Hemphill Katherine Stavoe Zain Khalpey

PII S0167-5273(14)00682-2

DOI doi 101016jijcard201404023

International Journal of Cardiology

14 days post injection

no pain

normal turgor

walking without pain

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

HOW DOES NEUROMODULATION WORKActively stimulating targeted nerve to produce a natural biological response Frequency 10HZ

Meta analysis by

Thalkral RCT by

Koel

RBecker

Injury site + charge

Flip polarity to ndash

Promote healing

Blastema - Tissue Regeneration ndash Salamanders

Blastema is the point of regeneration of lost parthellip

Reversing the electrical field creating a shift in polarity allows blastema to

growhellip

if Polarity does not shift then there is no healing

Same in a non healing fracture Dr Robert Becker (bone stimulation upstate NY medical center)

PLACENTAL ALLOGRAFT

OPHTHALMIC HEALING

mdash Tandon R Br J Ophthalmol 201195(2)199-204

At

Presentation

Final

VisitAmniotic Membrane

Transplant

Standard Medical

Care

Day 0 ndash 47cm Day 63 ndash Closed Margin

Patient LM - Comparative

22

Pre injection

painful scar

BedriddenFirst in Man Amniotic Stem Cell Injection Promotes Scar Remodeling and

Healing Processes in Late-Stage Fibrosis

Courtney Hemphill Katherine Stavoe Zain Khalpey

PII S0167-5273(14)00682-2

DOI doi 101016jijcard201404023

International Journal of Cardiology

14 days post injection

no pain

normal turgor

walking without pain

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

Blastema - Tissue Regeneration ndash Salamanders

Blastema is the point of regeneration of lost parthellip

Reversing the electrical field creating a shift in polarity allows blastema to

growhellip

if Polarity does not shift then there is no healing

Same in a non healing fracture Dr Robert Becker (bone stimulation upstate NY medical center)

PLACENTAL ALLOGRAFT

OPHTHALMIC HEALING

mdash Tandon R Br J Ophthalmol 201195(2)199-204

At

Presentation

Final

VisitAmniotic Membrane

Transplant

Standard Medical

Care

Day 0 ndash 47cm Day 63 ndash Closed Margin

Patient LM - Comparative

22

Pre injection

painful scar

BedriddenFirst in Man Amniotic Stem Cell Injection Promotes Scar Remodeling and

Healing Processes in Late-Stage Fibrosis

Courtney Hemphill Katherine Stavoe Zain Khalpey

PII S0167-5273(14)00682-2

DOI doi 101016jijcard201404023

International Journal of Cardiology

14 days post injection

no pain

normal turgor

walking without pain

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

PLACENTAL ALLOGRAFT

OPHTHALMIC HEALING

mdash Tandon R Br J Ophthalmol 201195(2)199-204

At

Presentation

Final

VisitAmniotic Membrane

Transplant

Standard Medical

Care

Day 0 ndash 47cm Day 63 ndash Closed Margin

Patient LM - Comparative

22

Pre injection

painful scar

BedriddenFirst in Man Amniotic Stem Cell Injection Promotes Scar Remodeling and

Healing Processes in Late-Stage Fibrosis

Courtney Hemphill Katherine Stavoe Zain Khalpey

PII S0167-5273(14)00682-2

DOI doi 101016jijcard201404023

International Journal of Cardiology

14 days post injection

no pain

normal turgor

walking without pain

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

Day 0 ndash 47cm Day 63 ndash Closed Margin

Patient LM - Comparative

22

Pre injection

painful scar

BedriddenFirst in Man Amniotic Stem Cell Injection Promotes Scar Remodeling and

Healing Processes in Late-Stage Fibrosis

Courtney Hemphill Katherine Stavoe Zain Khalpey

PII S0167-5273(14)00682-2

DOI doi 101016jijcard201404023

International Journal of Cardiology

14 days post injection

no pain

normal turgor

walking without pain

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

22

Pre injection

painful scar

BedriddenFirst in Man Amniotic Stem Cell Injection Promotes Scar Remodeling and

Healing Processes in Late-Stage Fibrosis

Courtney Hemphill Katherine Stavoe Zain Khalpey

PII S0167-5273(14)00682-2

DOI doi 101016jijcard201404023

International Journal of Cardiology

14 days post injection

no pain

normal turgor

walking without pain

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

Day 0 10mm x 11mm x 2mm

Day 60

Fully resolved

Patient BC (Day 0 vs 60)

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

Design Key for our new Paradigm

02 increase amplitude

(volume) of signaling in

recipients body to produce

appropriate proteinsbull

01 Upregulate

recipients body to

heal itself

Electrical Stimulus

amp

Biologic Stimulusbull

03 ldquostem cell function deteriorates with age driving events we know occur with agingrdquo bull Dr David Scadden -

Harvard Stem Cell Institute

04 ldquonerve cells appear to be one mdashsignal to others that itrsquos time to age ldquoDr Lee Rubin Harvard-Harvard Stem Cell

Institute

REVERSE THE PROCESShelliphelliphellipIS IT POSSIBLE

Hamza 68 reports improvement in the vascular function with neuromodulation therapy

causing neurotransmitter release

increased endorphins

inhibiting depolarization of the neurons

Not only can neuropathic pain be inhibited but the possibility of reversing the neuropathy

is potentially possible

Gordon et al 74 in their rat study -- demonstrated that axon regeneration may be

accelerated by brief periods of electrical stimulation

Deogaonkar et al 677576 increases in local capillary blood flow release of

neurotransmitters and cytokines and improved nerve function induced by electric

stimulation to the specific anatomic area 77

SNAKE OIL OR THE REAL DEAL

Functional electrical stimulation helps replenish progenitor cells in the injured spinal cord of adult

rats

Becker D1 Gary DS Rosenzweig ES Grill WM McDonald JW

Front Hum Neurosci 2015 Oct 199586 doi 103389fnhum201500586 eCollection 2015

Electrical Stimulation Elicits Neural Stem Cells Activation New Perspectives in CNS Repair

Huang Y1 Li Y2 Chen J1 Zhou H1 Tan S1

Exp Neurol 2014 Oct26012-8 doi 101016jexpneurol201209016 Epub 2012 Oct 1

Regeneration of the damaged central nervous system through reprogramming technology basic concepts and

potential application for cell replacement therapy

Matsui T1 Akamatsu W1 Nakamura M2 Okano H3

Int J Neurosci 2015125(10)774-83 doi 103109002074542014971121 Epub 2014 Oct 31

Co-treatment effect of pulsed electromagnetic field (PEMF) with human dental pulp stromal cells and FK506 on the

regeneration of crush injured rat sciatic nerve

Kim YT1 Hei WH Kim S Seo YK Kim SM Jahng JW Lee JH

Up-regulation of MSCrsquos with

Exposure to electrical fields

SNAKE OIL OR THE REAL DEAL

Functional electrical stimulation helps replenish progenitor cells in the injured spinal cord of adult

rats

Becker D1 Gary DS Rosenzweig ES Grill WM McDonald JW

Front Hum Neurosci 2015 Oct 199586 doi 103389fnhum201500586 eCollection 2015

Electrical Stimulation Elicits Neural Stem Cells Activation New Perspectives in CNS Repair

Huang Y1 Li Y2 Chen J1 Zhou H1 Tan S1

Exp Neurol 2014 Oct26012-8 doi 101016jexpneurol201209016 Epub 2012 Oct 1

Regeneration of the damaged central nervous system through reprogramming technology basic concepts and

potential application for cell replacement therapy

Matsui T1 Akamatsu W1 Nakamura M2 Okano H3

Int J Neurosci 2015125(10)774-83 doi 103109002074542014971121 Epub 2014 Oct 31

Co-treatment effect of pulsed electromagnetic field (PEMF) with human dental pulp stromal cells and FK506 on the

regeneration of crush injured rat sciatic nerve

Kim YT1 Hei WH Kim S Seo YK Kim SM Jahng JW Lee JH

Up-regulation of MSCrsquos with

Exposure to electrical fields

Bringing together Neuromodulation and Regenerative Biologics

Developing the possibility

of Stabilizing or reversing

the neuropathic process

02

Cellular

components

Pericytes-gt

MSC-gt growth

factors

03

Activity

Glucose control

Nutrition

Neuromodulation

Improve blood flow

with

Change in electrical

field polarity

frequency

Voltage and

Amplitude

Placental

Tissue

Messenger

microRNA

exosomes

RESULTS WIRELESS STIMULATOR TRIAL

6 patients with painful neuropathy unresponsive to standard of care

treatments

One leg on each patient was treated

Implant wireless stimulator along common peroneal and a second implant

placed along tibial nerve

Each patient used device a minimum 12 hours per day

5 patient reported a 80 reduction in pain at 6 weeks continuing to end of

study at 24 weeks

The implant 13cm long

29

Lateral AP

IMPLANT PLACEMENT ndash FIBULAR NERVE AKA

COMMON PERONEAL

YOU ARE TRAINED TO HEAL YOUR PATIENTS

Yes We need the evidence

But that does not mean you should ignore the possibilitieshelliphellip Allow yourself to think out of the Box

Donrsquot let third parties be the physicians and you the technician

Offer your patients all options covered or nothelliphellip That are safe and appropriate

Thank you for your time

Please feel free to ask your Questions

Bruce Werber DPM FACFAS

602-405-3247

docWerberGmailcom

THANK YOU FOR YOUR TIME

Dr Bruce Werber

All Americans want is the freedom and

security to pursue possibilityhelliphellip

RESULTS WIRELESS STIMULATOR TRIAL

6 patients with painful neuropathy unresponsive to standard of care

treatments

One leg on each patient was treated

Implant wireless stimulator along common peroneal and a second implant

placed along tibial nerve

Each patient used device a minimum 12 hours per day

5 patient reported a 80 reduction in pain at 6 weeks continuing to end of

study at 24 weeks

The implant 13cm long

29

Lateral AP

IMPLANT PLACEMENT ndash FIBULAR NERVE AKA

COMMON PERONEAL

YOU ARE TRAINED TO HEAL YOUR PATIENTS

Yes We need the evidence

But that does not mean you should ignore the possibilitieshelliphellip Allow yourself to think out of the Box

Donrsquot let third parties be the physicians and you the technician

Offer your patients all options covered or nothelliphellip That are safe and appropriate

Thank you for your time

Please feel free to ask your Questions

Bruce Werber DPM FACFAS

602-405-3247

docWerberGmailcom

THANK YOU FOR YOUR TIME

Dr Bruce Werber

All Americans want is the freedom and

security to pursue possibilityhelliphellip

29

Lateral AP

IMPLANT PLACEMENT ndash FIBULAR NERVE AKA

COMMON PERONEAL

YOU ARE TRAINED TO HEAL YOUR PATIENTS

Yes We need the evidence

But that does not mean you should ignore the possibilitieshelliphellip Allow yourself to think out of the Box

Donrsquot let third parties be the physicians and you the technician

Offer your patients all options covered or nothelliphellip That are safe and appropriate

Thank you for your time

Please feel free to ask your Questions

Bruce Werber DPM FACFAS

602-405-3247

docWerberGmailcom

THANK YOU FOR YOUR TIME

Dr Bruce Werber

All Americans want is the freedom and

security to pursue possibilityhelliphellip

IMPLANT PLACEMENT ndash FIBULAR NERVE AKA

COMMON PERONEAL

YOU ARE TRAINED TO HEAL YOUR PATIENTS

Yes We need the evidence

But that does not mean you should ignore the possibilitieshelliphellip Allow yourself to think out of the Box

Donrsquot let third parties be the physicians and you the technician

Offer your patients all options covered or nothelliphellip That are safe and appropriate

Thank you for your time

Please feel free to ask your Questions

Bruce Werber DPM FACFAS

602-405-3247

docWerberGmailcom

THANK YOU FOR YOUR TIME

Dr Bruce Werber

All Americans want is the freedom and

security to pursue possibilityhelliphellip

YOU ARE TRAINED TO HEAL YOUR PATIENTS

Yes We need the evidence

But that does not mean you should ignore the possibilitieshelliphellip Allow yourself to think out of the Box

Donrsquot let third parties be the physicians and you the technician

Offer your patients all options covered or nothelliphellip That are safe and appropriate

Thank you for your time

Please feel free to ask your Questions

Bruce Werber DPM FACFAS

602-405-3247

docWerberGmailcom

THANK YOU FOR YOUR TIME

Dr Bruce Werber

All Americans want is the freedom and

security to pursue possibilityhelliphellip

THANK YOU FOR YOUR TIME

Dr Bruce Werber

All Americans want is the freedom and

security to pursue possibilityhelliphellip