WHAT IS AD?

Alzheimer’s Disease (AD) is a neurodegenerative disease that primarily affects individuals over 65 years of age. It is characterized by a progressive loss of memory that is due to the dysfunction and loss of brain cells (neurons) in brain areas important for cognition. While the exact cause of AD is unclear, many AD researchers believe the root cause is aggregation of two abnormal proteins (Aβ and p-tau) that are present inside neurons. Initially, single Aβ proteins self-aggregate to form Aβ oligomers, which then stimulates phosphorylation of the second protein into p-tau and aggregation of single p-tau proteins into p-tau aggregates (See figure on right). Multiple toxic processes are induced by these Aβ and p-tau oligomers that result in the dysfunction or death of neurons. The presence of both these oligomers inside neurons is an early pathogenic event, occurring before overt signs of AD memory loss.

To our knowledge, there is no known AD therapeutic that has been shown to break-up Aβ and p-tau oligomers inside neurons – which is where they appear to cause the dysfunction and death of neurons. NeuroEM has evidence that Transcranial Electromagnetic Treatment (TEMT) breaks up both Aβ and p-tau oligomers inside (and outside) neurons. Although this is probably TEMT’s primary mode of action against AD, there are several other beneficial actions of TEMT that NeuroEM has identified, including an increase in neuronal energy production (mitochondrial enhancement). This is important because a very early sign of AD, perhaps a decade before AD diagnosis, is reduced energy production in the brain as shown in PET scans.

AD disease has three stages:

  • Pre-symptomatic:

    No cognitive impairment, but loss/dysfunction of neurons starts to occur. This stage begins 10 or more years before any noticeable memory loss.

  • Mild Cognitive Impairment (MCI):

    Modest impairment of short-term (immediate) memory as neuronal loss/dysfunction continues.

  • Alzheimer’s Disease:

    Substantial short-term and long-term memory impairment, with eventual total loss of intellect – all this over the course of 2 to 20 years.

WHO GETS AD?

Alzheimer’s Disease (AD) is indiscriminate in striking everyone irrespective of their race, gender, location, occupation, income, or activities. In 2019, an estimated 6 million Americans have AD, which accounts for 70 percent of all cases of dementia. One in eight people aged 65 and older have Alzheimer’s disease and half of people age 85 and older have AD. Another 5-6 million American have Mild Cognitive Impairment (MCI), which precedes AD. Thus, NeuroEM Therapeutics’ target market in the U.S. currently numbers between 10-11 million Americans.

The number of people suffering from AD is growing rapidly, with the number of U.S. patients expected to triple by 2050. One in three Americans will die with AD, with one new case being diagnosed every 68 seconds. It has recently been estimated that over 500,000 Americans die of Alzheimer’s complications every year, and AD is the third leading cause of death in the U.S. The cost of caring for AD patients today is $200 billion/year and is expected to grow to $1.2 trillion/year by 2050 if an effective treatment is not found. The U.S. market for AD drugs in 2015 was approximately $3 billion – The market could approach $20 billion annually with the approval of a disease-modifying therapeutic against the disease.

CURRENT AD DRUGS

There is no effective preventative or treatment for AD, with current FDA-approved drugs only temporarily slowing the rate of cognitive decline, if at all. These AD drugs only mask the disease’s symptoms and are not “disease-modifying”. To date, all clinical trials involving drug treatment in AD patients have universally failed to provide long-term benefit. AD drugs not only do not get into the brain well, but more importantly they have extreme difficulty getting inside the brain’s neurons – which is where oligomeric Aβ and oligomeric p-tau reside as the probable causes of AD memory impairment. Even if they did get into neurons, current AD drugs generally do not target these two oligomeric proteins. NeuroEM’s electromagnetic technology, which we believe directly and uniquely attacks both Aβ and p-tau oligomers inside neurons, may represent an effective treatment in the near future for AD patients.

NEUROMODULATION AGAINST AD

In addition to TEMT, there are several other neuromodulatory (non-drug) approaches that are currently being clinically investigated as potential treatments for AD. Transcranial Magnetic Treatment (tMS) involves clinical visits to administer magnetic waves to the brain through several large magnets placed on the head during each treatment. Deep Brain Stimulation (DBS) requires invasive surgical implantation of several electrodes deep into the brain; the electrodes are then connected to a subcutaneously-placed battery/activation unit. Both approaches provide stimulation effects on neuronal activity, but have thus far not been shown to affect the memory decline of AD patients in Phase II/III clinical trials or to affect the AD process. Another approach, Transcranial Ultrasound (tUS), applies ultrasound to the head in order to open up the blood/brain barrier, which apparently allows some as yet unknown agent to enter the brain from the blood to activate certain brain cells. tUS requires clinical MRI monitoring before and after a treatment, with potentially toxic gadolinium being infused prior to scanning. The first clinical trial with tUS in AD patients is currently underway. Clinical trials are also underway with photomodulation, which involves treatment with flickering LED light at 40 Hz via glasses (Cognito Therapeutics) or transcranial treatment (Vielight).

tMS

DBS

tUS