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The Race to Restore Memory

By MARILYN SOLTIS
It’s one of the most frightening of possibilities. You or a loved one gradually forgetting a lifetime of memories. Alzheimer’s is a brain-wasting disease that gradually takes away a person’s ability to think and take care of themselves or others.
 
Many of the scientific world’s best and brightest are searching for answers to this affliction that strikes at the heart of an aging population.  Research cuts across many areas, from pharmaceuticals to diet and exercise, herbs, holistic remedies, stem cell therapy, anything that might restore fading cognitive function.
   
Perhaps one of the most exciting and innovative developments is the culmination of ten years of work by the University of California,  North Carolina’s Wake Forest University and other scientists across the country. MIT lauded their breakthrough as one of the top ten technological breakthroughs of 2013.
   
These neuroscientists believe they will be able to implant a small memory device into a group of human volunteers and have it widely available within a decade. CNN reported that the team of American neuroscientists believe they have discovered how “long-term memories are made, stored and retrieved and how to replicate this process in brains that [are]damaged, particularly by stroke or localized injury.”
   
Ted Berger, professor of biomedical engineering at the University of Southern California in Los Angeles said they record a memory being made, in an undamaged area of the brain, and use the data to predict what a damaged area downstream should be doing. Electrodes are used to stimulate the damaged area to replicate the action of undamaged cells. They have looked at how electrical signals travel through neurons to form those long-term memories and then use mathematical modeling to mimic the movements using electronics.
   
Today, about 80,000 people have brain implants that provide deep brain stimulation to treat epilepsy and Parkinson’s disease so the concept is already in place. The neuroscientists now have to shrink their sequipment down to a manageable device.
   
The implant will not work for people with advanced dementia but Berger thinks that drugs and implants could be used together to treat early dementia.  The action of the cells around the damaged area could be enhanced by the drugs and the memory implant would replace lost cells in the middle of the damaged area.

Stem Cell Research

   
The Alzheimer’s Association funds research in stem cell therapy and have issued statements saying the organization believes stem cells have the potential to repair brain damage caused by neurological conditions.
   
The association is hopeful about future advances. It states, “In Alzheimer's disease, nerve cells die in a random way, interrupting the complex inter-connections of nerve cells in the cortex (the outer layer of the brain). It is this network of cells that facilitates our memories, personalities and behavior patterns. Because of the loss of many different nerve cell types in the brain in Alzheimer's disease and the impact that the disease has on communication between cells, developing stem cell therapy for Alzheimer's disease is more complicated and challenging than for some other neurological conditions.” They see long term possibilities for stem cell research, although they do not foresee Alzheimer’s and other forms of dementia as being the first to benefit from this area.
   
The Italian Parliament sees it differently. On May 16 of this year the Italian Senate voted in favor of a new bill already approved by the Chamber of Deputies to set aside three million euros for a clinical trial of stem cell treatment devised by the Stamina Foundation in Turin. It is the first time a parliament has ordered a clinical trial.
   
The Stamina Foundation says their treatment transforms a patient’s own mesenchymal stem cells from bone marrow into newly minted nerve cells to treat neurodegenerative diseases including Alzheimer’s. The International Society of Stem Cell Research disputes this claim saying there is “no compelling evidence from clinical trials that such cells provide benefit to patients with neurological conditions”.

Drug Research


The Alzheimer’s Association funds researchers looking at new treatment strategies and advocates for increased federal funding for Alzheimer’s research.  According to researchers the currently available FDA-approved drugs that treat the symptoms of the disease may temporarily help memory and thinking problems in half the people who take them, but don’t treat the underlying causes of Alzheimer’s.
   
Scientists are now aiming to modify the disease process by targeting different brain changes caused by Alzheimer’s resulting in a cocktail of medications similar to many cancer treatments and AIDS. The group lists promising targets currently under study:

  • Beta-amyloid is the chief component of plaques, a hallmark of Alzheimer’s. Researchers are developing medications aimed at every point in amyloid processing including preventing beta-amyloid from clumping into plaques and using antibodies against beta-amyloid to clear it from the brain.
  •   Inflammation.  There has been a great deal of research about the molecules involved in the body’s overall inflammatory response and they are now looking into what aspects of inflammation are specific to the brain that may point to anti-inflammatory treatments.
   •   Insulin resistance.  Researchers are looking into the role of insulin in the brain and how brain cells use sugar and produce energy.

When it’s Too Good to Be True
   
With so much at stake and millions of aging boomers afraid Alzheimer’s will strike them or a family member, it’s critical that scientific research and journals conform to strict standards. A year ago the leading journal Science published an article about a drug called bexarotene, a skin cancer drug that cut the amount of beta-amyloid in mice by half in just three days. The drug reversed Alzheimer’s symptoms, allowing the mice to resume their nest building. Even their sense of smell was restored.
   
Even though the drug was never tested on people suffering from Alzheimer’s disease, patients desperately wanted the drug and some doctors were willing to prescribe it.
   
Just one year later, in May of this year, the same journal recommended in a “technical comment” that bexarotene should not be tested on patents. When fellow scientists tried to reproduce the same results they failed.
   
This has raised questions about the strategy of targeting this amyloid in the fight against Alzheimer’s. Some scientists question whether these plaques are a cause or effect of the disease.
   
Another major disappointment in the war against Alzheimer’s was Baxter International’s announcement this May that it will stop late stage trials of an antibody treatment after it failed to slow mental decline in patients. The drug, Gammagard, was the only remaining drug in late stage development for the disease.

Some Recent Studies about Cognitive Health

Eat Less
   
Eating less may be one of the key factors in decreasing changes in the brain that lead to aging and neurodegenerative diseases such as dementia and Alzheimer's. A recent study published in the Journal of Neuroscience showed that fewer calories delayed the loss of brain cells in mice as well as preserving cognitive function
   
Conducted by the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology and Howard Hughes Medical Institute, researchers found that calorie restriction activates an enzyme called Sirtuin 1 (SIRTs1) which studies have linked to protection from age-related impairments. A pharmacological SIRT-1 activation compound could be a useful tool for humans if proven safe. The mice were fed 30% fewer calories in the study.

•   Tau protein, the chief component of neurofibrillary tangles, is a hallmark of brain abnormality. Scientists are looking at ways to keep tau molecules from collapsing and twisting into tangles.

    •  Brain imaging and biomarkers. Clinical trials are underway which look at various brain imaging studies and the testing of blood or spinal fluid hoping to diagnose Alzheimer’s in its earliest and most treatable stages.


Skin Cancer

Researchers at the Albert Einstein College of Medicine in New York found that people who had skin cancer were nearly 80 percent less likely to develop Alzheimer’s than those who did not have it, according to research published in the May issue of Neurology.

Obesity


Increasing rates of obesity could significantly increase the number of people living with dementia according to evidence presented at the European Congress on Obesity in Liverpool. Jessica Smith, Research Officer at the Alzheimer’s Society, said: “It’s easy to see the immediate impact of piling on the pounds but we can’t afford to ignore the long-term effects. Evidence shows that obesity increases the risk of developing dementia. This study highlights the impact obesity will have on the numbers of people with the condition in the future. The changes that cause dementia develop over many years, so maintaining a healthy weight and exercising regularly—especially in mid-life—are hugely important in reducing your risk.”

Mediterranean Diet

Eating a Mediterranean Diet of fruits, vegetables and olive oil while avoiding red meat and saturated fat has been linked with preserving cognitive function according to a study published in Neurology. Academics at the University of Alabama and the University of Athens looked at the dietary habits of 17,478 people to see how closely they followed a Mediterranean diet and gave participants tests measuring memory and thinking abilities over an average of four years. The study found that healthy people following a Mediterranean diet were 19 percent less likely to develop thinking and memory problems.

   
Cinnamon : Two compounds found in cinnamon, cinnamaldehyde and epicatechin, may be useful in delaying or preventing the effects of Alzheimer’s according to UC Santa Barbara scientists Roshni George and Donald Graves in a study published in the Journal of Alzheimer’s Disease, which states that the compounds have been shown to prevent the development of the filamentous “tangles” that characterize Alzheimer’s in brain cells. Older people are more susceptible to these twists and tangles, and Alzheimer’s patients develop them in larger amounts.
   
Other studies have shown a high correlation between Type 2 Diabetes and the development of Alzheimer’s. The elevated glucose levels associated with diabetes lead to oxidative stress, a common factor in both diabetes and Alzheimer’s. Cinnamon has been shown to be beneficial in managing blood glucose.

Chemical Approach A team of scientists at the University of Liverpool and Callaghan Innovation have developed a new chemical approach, harnessing the ability of sugars, based on the blood-thinning drug heparin to block the actions of BACE, responsible for creating the amyloid protein that causes memory loss.


Published: June 15, 2013
Issue: Summer 2013 Issue