Sunday, August 30, 2015

Forecast # 1: Preventing Alzheimer's Disease

A. Sources:

"Lifting the Curse of Alzheimer's," Gary Stix, Scientific American, May 2015, pages 50-57

Images courtesy of Alzheimer's Association at

What is Alzheimer's Disease?

Take the Brain Tour to see how Alzheimer's Disease affects the brain:

Watch the video to understand what happens to a person with Alzheimer's:

B. Analysis: 

A treatment for the prevention of Alzheimer's Disease is possible! Right now, a groundbreaking study is being conducted in the Colombian province of Antioquia by Francisco Lopera, a neurologist who has devoted his research, since 1987, to working with over 5,000 members from 26 extended families who are genetically pre-disposed to a familial form of Alzheimer's. This mutation of the disease, called Paisa, has been traced back to the time of the conquistadors in the 16th century and is unique to the people of this region. It was found to be located on chromosome 14 by Lopera and his team. If the gene is inherited it is guaranteed that one will develop early onset Alzheimer's. 20% of the population of this region develops Alzheimer's before the age of 50.

Lopera, a native of Antioquia, is driven to focus on prevention the disease, rather than treatment of the progression of it, by the mere fact that of the 413 clinical trials that have taken place from 2002 to 2012, whose objective is to stop the progression of the disease, more than 99 percent have failed. His conclusion: treating the disease may be too late once the symptoms have become apparent and that the focus must be shifted toward prevention. The 26 Colombian families are ideal subjects for Lopera's study and clinical trial because Alzheimer's is predictable in this group and researchers can work backward 10 to 15 years to calculate when to start giving the drug, crenezumab, to stop the disease. They are also ideal in that they have close-knit family structures and are more likely to show up for treatments and testing, because of their natural inclination for caring for the sick, in contrast to the depersonalization of medicine taking place in the U.S. and Europe. As a result, this has increased the chances for accuracy in the study.

Lopera's trial, The Alzheimer's Prevention Initiative, began administering the drug crenuzumab (and placebos) to participants of the trial in 2013. Brain scans and spinal taps will determine if the drug stops the accumulation of beta-amyloid, the amino acid which causes plaque build up in the brain, causing the cognitive effects of Alzheimer's. Psychological tests are also conducted to observe changes in cognitive ability.

If, after 5 years of administering the drug, the course of Alzheimer's is found to be altered or halted in the subjects, then the clinical trial would expand to include healthy elderly people who do not have the Paisa mutation but have shown evidence of recent pathological changes in the brain.

My life is personally affected by vascular dementia, a disease with similar symptoms to Alzheimer's. My mother has received a formal diagnosis of vascular dementia in the past year.

C. Bullet Answers:

Global: In 2015, 46.8 million people in the world are living with dementia. The world will spend 818 million U.S. dolIars on treating Alzheimer's this year.

National: 5.3 million in the United States are currently living with the disease.

Local and Personal: In Minnesota, it is believed that there are more than 100,000 people living with the Alzheimer's and other forms of dementia. On a personal level, it affects everyone living with the disease and their caretakers. The average family caring for a member with Alzheimer's or dementia can expect to spend, at least, $215,000 on care and treatment of the disease. Not only does it cost financial resources but it costs time and energy, and the emotional toll it takes on families is immeasurable.

What can happen in the next 2 years: Lopera's trial will continue, providing insights for the advancement in the prevention of Alzheimer's. Other research throughout the world will continue in the advancement of treatment of those already suffering from the disease.

What can happen in the next 20+ years: The number of people living with dementia is expected to almost double every 20 years, reaching 74.7 million and 131.5 million by 2050. The resources devoted to Alzheimer's is expected to increase to 2 trillion U.S. dollars by 2030. If Lopera's trial proves to be successful, then it will expand to include non-familial Alzheimer's and other types of dementia. This could result in an actual decline in the number of people suffering from the disease, possibly even an obliteration of the disease. This could ultimately, decrease the amount of or even eliminate the need for resources specifically needed for Alzheimer's research and treatment.

Possible Positive Outcomes:
- It is possible that Lopera's clinical trial, concluding in 2021, will result in the shift in focus to prevention of the disease, therefore this population will not have to deal with the negative effects of the disease at all. If Alzheimer's can be prevented, then resources that are now being spent to treat and care for Alzheimer's can be directed to the research and treatment of other diseases.
- On a more personal level, the likelihood of my mother's quality of life being affected by the results of the trial is slim, because phase one's results of Lopera's trial will not be confirmed until 2018 and the trial will be concluding in 2021. It may affect myself, or my children's chances of developing dementia and may increase our chances for long, normal and healthy lives.
- Positive scenario: a drug with no negative side effects is developed to stop the manifestation of Alzheimer's and dementia.
- Better scenario: there a way of eliminating or mitigating the gene that is responsible for the disease, thus preventing future generations from having Alzheimer's all together. This has been done with other genetic diseases through preimplantation genetic diagnosis in which non-diseased embryonic cells would be implanted in a mother's uterus or through gene therapy, in which a working version of a gene is introduced into the DNA to overcome the disease versions of the gene.
- Best case scenario: A "gene zapper" which corrects flawed genes in utero when they are detected. There could be a test conducted at a prenatal visit and the repair could be done on the spot at an affordable price. Gene zappers have been used to zap the genes responsible for scent in mosquitos to help prevent the spread of disease, so it is not out of the realm of possibility.

Possible Negative Outcomes:
-The drug, crenuzumab, will not have the ability to prevent the disease, resulting in going back to the drawing board for researchers to try to find a different approach to prevention and/or curing Alzheimer's and dementia.
- Preimplantation genetic diagnosis is too expensive.
- Gene therapy is not perfect. It is difficult to introduce new genes into DNA. Working copy does not always mask bad copies of genes and bad copies would always be present, with potential to pass on to future generation.
- "Gene zapper" has costs unknown. May be cost prohibitive to low-income population. Mistakes could occur, affecting wrong genes and causing unintentional harm to healthy genes.

Region of the Future:

1. What else can be done to advance the prevention of Alzheimer's?
2. What are the possibilities of altering genetics to avoid the disease manifesting itself all together?
3. Are we messing with mother nature and the natural selection process by potentially being able to alter our genetic makeup?
4. How will removing Alzheimer's as a means of natural selection affect population growth?

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Just keeping things on the up and up since this is for my students to communicate first.