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