Transcranial Electromagnetic Treatment (TEMT) against

Alzheimer's Disease: Pre-Clinical Efficacy and Clinical Trial in

Progress

Dr Gary W. Arendash, President and CEO

Seminar Topics

Alzheimer’s symptoms and pathogenesis

AD drugs and why they have thus far failed

Neuromodulation therapies

TEMT: Cognitive and Neuropathologic Benefits in mice

Mechanisms of TEMT action

Health concerns of TEMT

TEMT effects on human brain function

Phase I Clinical Trial with TEMT in Alzheimer’s patients

Concluding Remarks

Alzheimer’s Disease Characteristics

Three Stages:

Pre-symptomatic

Mild Cognitive Impairment (MCI)

Alzheimer’s Disease

• Mild AD

• Moderate AD

• Severe/Advanced AD

Typical AD:

A gradual,

progressive loss of

memory over 2-20

years

1

Around 400,000 Australians have dementia

2nd leading cause of death

2

3

Brain Areas Most Impacted by Alzheimer’s Disease

Cerebral Cortex

Hippocampus

Normal Brain Alzheimer’s Brain

Aβ Aggregation:

The Root Cause of AD

Monomer

Dimer

Oligomer

Diffuse Plaque

Compact Plaque

Toxic

Current State of Therapeutics against AD

Four FDA-approved drugs:

- Only mask symptoms; No new drugs approved in 15+ years

Over 100 drugs have failed in AD clinical trials

Therapeutic approaches

- Beta-secretase inhibitors AZD3293, MK-8931

- Antibodies against A BIIB037, Solanezumab

- Metal Chelators PBT2

- Tau aggregation inhibitors LMTM

- Receptor agonists/antagonists ANAVEX 2-73

Why is there still no drug to prevent or treat AD?

1) Crossing the blood/brain barrier; getting into neurons

2) Wrong therapeutic target

3) A single mechanism of action

Neuromodulatory Approaches against AD

Transcranial Direct Current Stimulation (tDCS)

Transcranial Magnetic Stimulation (tMS)

Deep Brain Stimulation (DBS)

Transcranial Ultrasound (tUS)

Transcranial Electromagnetic Treatment

(TEMT)

TEMT = Transcranial RadioFrequency Treatment(TRFT)

TEMT Experimental Conditions

918 MHz (ISM band), pulsed at 217 Hz and modulated

Electric Field of 17–35 V/m; 0.25-1.05 W/kg SAR

Daily 1-hour treatments in early morning & late afternoon

This pre-clinical research involved 7 research laboratories

Long-term TEMT Studies

TEMT started TEMT Duration

Young Adulthood 2M old 7½ months

Mature Adulthood 5M old 8½ months

Old Age 15-17M old 1 month

Advanced Old Age 21-26M old 2 months

Alzheimer’s “Transgenic” Mice and Normal Mice

TEMT Protects AD Mice from Memory Loss

Cognitive Interference Task

1) Pool 1 (3-Trial Recall)

2) Pool 2 (Proactive Interference)

3) Pool 1 (Retroactive Interference)

4) Pool 1 (Delayed Recall)

Tg + TEMT

D

TEMT Improves Memory in Impaired AD Mice

SUMMARY:

TEMT protects against and reverses

cognitive impairment in AD Tg mice,

while even benefiting normal mice

Long-term TEMT does not induce deleterious effects

in brain or peripheral tissues of mice

No effects on brain DNA repair, AO enzymes, oxidative damage

No histologic/gross changes in brain or peripheral tissues

No increase in blood oxidative stress

No change in brain temperature during treatment

Therefore, TEMT provides

cognitive benefits through

“NON-THERMAL” mechanisms

Mechanisms of TEMT Action

1) Disaggregation of A

Direct: Vibration of H-bonds in -sheet proteins bond weakening

(Yarovsky, 2016)

Indirect: Heat Shock Protein production (HSP70,90)

TEMT effects may be Direct or Indirect:

Mechanisms of TEMT Action

2) Mitochondrial Enhancement

Mechanisms of TEMT Action

3) Increased Neuronal Activity

BOTTOM LINE: Multiple Mechanisms of TEMT Action

Reduction in brain neuronal activity is an early

characteristic of AD – correlates with cognitive decline

Control

TEMT

RF Exposure in Animals & Cell Cultures: Hazardous?

Some studies (acute exposure, 2450 MHz exposure) adverse effects

At 900 MHz:

Our own studies demonstrate no deleterious effects of TEMT in mice

Others: No long-term impairment of cognitive performance in rodents

Others: No long-term effects on immune function, oxidative stress, BBB

Others: No DNA damage or genotoxicity in cell cultures

What about cancer in rodents after long-term RF (900 MHz) exposure?

RF exposure (5M to LL) does not initiate or promote any type of cancer

Cancer induction requires breaking of covalent bonds between atoms

- X-rays, UV/gamma waves: frequency/high energy; RF = non-ionizing

Einstein (1905): EM frequencies required to break bonds!!

National Toxicology Program’s Report of Partial Findings (May, 2016)

- Rats given 900 MHz exposure 9 hours/day from gestation through entire life

- 2% of exposed rats developed brain cancer; no control rats did (2% is normal)

Are RF Waves (Mobile Phones; TEMT) Deleterious to Human Health?

One antenna of our TEMT device = GSM 900 phone – same freq./power

Many recent reviews & statements from NIEHS, FDA, FCC, CDC, NCI

No adverse health effects of MF’s (cognition, cancer)

Brain temperature: 0.1-0.2 C at 1.6 W/kg; 1C at 16 W/kg

Beginning in 2004, Swedish researchers reported a doubling in risk

of brain cancer with 10-15 years of MF use

IARC 2011 Report (Class 2B)

Since 2010, larger and better-designed human studies have

repeatedly concluded that RF waves (900 MHz) do not cause brain

cancer

The Interphone Study - >10 years, 13 countriesDenmark study of 358,000 cell phone subscribers – 17 yearsThe Million Women Study – 7 year follow-upNCI’s Surveillance, Epidemiology, & End Results Program (1987-2007) d

National Cancer Institute (2015) “To date, there is no evidence from

studies of cells, animals, or humans that radiofrequency energy can

cause cancer”

Brain Tumor

Incidence in

Sweden from

1970 – 2009:

No increased

risk since 1987 (when cell phones

were introduced)

(Ahlbom & Feychting, 2011)

Effects of RF exposure (900/1900 MHz) on Human Brain Function

All controlled human studies in “Normal” individuals,

acute administration, unilateral

No cognitive effects observed (positive or negative)

Decreases in rCBF observed (PET)

Increases in brain metabolism (FDG-PET) reported

Increases in EEG alpha-wave activity reported

No “long-term” controlled studies in humans. HOWEVER,

1) Heavy MF use over 2 yrs better cognitive perform.

2) MF use 10 yrs 30-40% less risk of hospital. for AD

Phase I Clinical Trial of TEMT in AD Patients – “In Progress”

Subjects: 12-14 patients with mild/moderate Alzheimer’s Disease

- All to receive TEMT (915 MHz, 1.6 SAR); Safety &efficacy evaluated

Treatment Period: 2-months; twice daily in home by caregiver

Primary Outcome Measures: Change from Baseline to Week 8 in

cognitive performance (ADAS-cog, others)

Secondary Outcome Measures: Change from Baseline to Week 8 in:

Brain energy metabolism (2DG-PET)

Functional and anatomic MRI scans

Blood and CSF analysis of AD markers

Study Completion Date: March, 2017; Results presented at AD/PD

For more information on this trial: ClinicalTrials.gov

Protocol #02958930

NeuroEM’s Collaborative Institutions/Companies:

TEMT Device Development

Electromagnetics

Clinical Trials

Concluding Remarks

Our pre-clinical studies indicate that TEMT protects against and reverses

memory impairment in AD mice

Multiple mechanisms are involved, several of which are not provided by any

other AD therapeutic in clinical trials

Based on both human and animal studies, TEMT (915 MHz) appears to be safe

and not hazardous to human health

Our on-going Phase I clinical trial – first long-term RF treatment to the entire

human brain

TEMT may be therapeutic against a number of other neurodegenerative

disorders having aggregation of toxic proteins in their pathogenesis (Down’s

Syndrome, TBI, PD)

“Every great advance in science has issued from a new audacity of imagination”

- John Dewey