It Took 90 Years To Accept The Dreaded Disease Discovered In A Mental Asylum

In 1908 Dr. Alois Alzheimer discovered a memory erasing, attitude destroying and human dignity stealing deadly disease coined after his name, researching on a patient in a mental asylum.

The disease, in the absence of still any effective treatment, converts a lively human being gradually into a vegetative state, ruthlessly, though the life keeps ticking erratically before it finally extinguishes.

Despite advancement of medical science at a break neck speed, is it not quite surprising that it took 90 years, from 1908 to 1998, to formally accept the root cause of Alzheimer’s disease in the medical science?

Still the greatest mystery of this disease is why it strikes mostly at an advancing age. Other risk factors include ailments such as, diabetes, depression, cardiac conditions and sedentary life style.

I deliberated on this issue in one of my earlier blog posts titled, “Alzheimer’s Disease: Robs Memory: Steals Dignity: Escapes Treatment” of August 11, 2014, though on a different perspective.

A flash back on the disease:

A September 2014 article of Dr. Rod Tanchanco, published in the ‘History News Network’, elucidates how Dr. Alzheimer discovered this deadly disease in a Mental Asylum.

As Dr. Rod Tanchanco narrated, the germination of this discovery started with an orderly and industrious homemaker Auguste, a 50 year old housewife, who started making uncharacteristic mistakes in preparing home meals – a task in which she had been quite proficient for long.

With the progress of time, Auguste gradually started wandering aimlessly around the apartment, leaving many unfinished work in the house. Her attitude and behavioral pattern also started changing noticeably. Concerned with these changes, her husband Carl had no other choice but to take her to the local mental asylum.

The physician’s in the asylum described her as suffering from a weak memory, persecution mania, sleeplessness, and restlessness that rendered her unable to perform physical or mental work. However, the psychiatrist sensed that there was something special about Auguste and Dr. Alois Alzheimer decided that he should see Auguste for himself. The limited treatments included the use of sedatives and warm baths.

After thorough examination, what struck Dr. Alzheimer was Auguste’s relatively young age (51) as he had seen many cases of mental deterioration in much older patients that prompted him to theorize that age-related thickening of the brain’s blood vessels led to brain atrophy.

After about five years of progressive mental and physical decline, Auguste died in 1906. The official cause of death was stated as blood poisoning due to bedsores. However, Dr. Alzheimer suspected that behind her mental illness was a strange disease and perhaps examining her brain would offer some clues.

Discovery of the disease:

When Dr. Alzheimer examined Auguste’s brain sections under the microscope, his inkling was proved to be a reality. He described changes in the neurofibrils – the protein filaments found in brain cells. He also saw peculiar deposits that he referred to as “millet seed-sized lesions.” These pathologic findings, which are now known as neurofibrillary tangles and amyloid deposits, characterize the brains of patients suffering from Alzheimer’s Disease.

Skeptical initial response:

As Dr. Rod Tanchanco highlights, Dr. Alzheimer’s discovery was not immediately well received, as correlating mental or neurologic disorders with histopathologic findings was not firmly established nor accepted by his peer groups at that time.

Acceptance after long 90 years:

Ninety years later, in 1998, researchers re-examined Auguste’s original brain sections and confirmed the presence of neurofibrillary tangles and amyloid plaques. There is still no cure of this life-threatening disease, and the burden on the afflicted continue to remain mind-boggling.

According to Dr. Tanchanco, one of the most prominent psychiatrists in the early 1900s called Emil Kraepelin, first mentioned the term ‘Alzheimer’s Disease’ in the 1910 edition of his textbook on psychiatry. The disease was still poorly understood, but one of the most famous medical eponyms was born with it.

Where are we today?

All current treatments for Alzheimer’s cannot stop the underlying decline and death of brain cells. Thus, as more cells die, Alzheimer’s continues to progress.

Experts are cautiously hopeful about developing Alzheimer’s treatments that can stop or significantly delay the progression of Alzheimer’s. A growing understanding of how the disease disrupts the brain has led to potential Alzheimer’s treatments that short-circuit fundamental disease processes.

A laudable initiative has come to the fore recently in this arena. Having experienced something like the ‘law of diminishing return’ in pursuit of high resource intensive R&D projects aimed at critical disease areas such as Alzheimer’s, 10 big global pharma majors reportedly decided in February 2014 to team up with the National Institutes of Health (NIH) of the United States in a ‘game changing’ initiative to identify disease-related molecules and biological processes that could lead to future medicines.

This Public Private Partnership (PPP) for a five-year period has been named as “Accelerating Medicines Partnership (AMP)”. According to the report, this US federal government-backed initiative would hasten the discovery of new drugs in cost effective manner focusing first on Alzheimer’s disease, Type 2 diabetes, and two autoimmune disorders: rheumatoid arthritis and lupus. The group considered these four disease areas among the largest public-health threats, although the span of the project would gradually expand to other diseases depending on the initial outcome of this project.

New drug development concepts:

A. Two new treatment approach strategies:

The protein beta-amyloid (plaques) has long been considered a sign of Alzheimer’s disease. Some of the new Alzheimer’s treatments in development target microscopic clumps of plaques.

According to Mayo Clinic, beside other studies, following are the two newer strategies aimed at beta-amyloid (plaques):

  • Immunization strategies:

Most current immunization studies focus on administering antibodies against beta-amyloid from outside sources instead of enhancing a person’s immune system.

One large research effort is exploring the value of intravenous (IV) infusions of a product derived from donated blood. This product contains naturally occurring anti-amyloid antibodies from the donors.

Some other studies are investigating laboratory-engineered (monoclonal) antibodies.

  • Production blockers:

This may reduce the amount of beta-amyloid formed in the brain. Research has shown that beta-amyloid is produced from a “parent protein” in two steps performed by two different enzymes. Several experimental drugs aim to block the activity of the two enzymes.

B. The concept of heart-head connection:

Another interesting area, among many, that the Mayo Clinic highlights is the concept of heart-head connection.

Growing evidence suggests that brain health is closely linked to heart and blood vessel health. Our arteries nourish our brain. The risk of developing Alzheimer’s appears to increase as a result of many conditions that damage the heart or arteries. These include high blood pressure, heart disease, stroke, diabetes and high cholesterol.

In addition, a strong genetic Alzheimer’s risk factor is one form of a gene for a protein that carries cholesterol in the blood (apolipoprotein E). Strategies under this concept include:

- Available drugs for heart disease risk factors: Researchers are investigating whether drugs now used to treat high blood pressure, diabetes and high cholesterol may also help people with Alzheimer’s or reduce the risk of developing the disease.

- Drugs aimed at new targets: Additional projects are looking more closely at how the connection between heart disease and Alzheimer’s works at the molecular level to find new drug targets.

- Lifestyle choices: Researchers have explored whether lifestyle choices with known heart benefits, such as exercising on most days and eating a heart-healthy diet, may help prevent Alzheimer’s disease or delay its onset.

A large new database of Alzheimer’s disease patients:

Meanwhile, the Coalition Against Major Diseases (CAMD), which is a formal consortium of pharmaceutical companies, research foundations and patient advocacy/voluntary health associations, with advisors from federal agencies, has released a new database of more than 4,000 Alzheimer’s disease patients who have participated in 11 industry-sponsored clinical trials.

According to the Critical Path Institute, which oversees the coalition, this is the first database of combined clinical trials to be openly shared by pharmaceutical companies and made available to qualified researchers around the world. It is also the first effort of its kind to create a voluntary industry data standard that will help accelerate new treatment research on brain disease, as patients with other related brain diseases are expected to be added.

A large number of researchers believe that sharing these data from more than 4,000 study participants will speed development of more-effective therapies.

CAMD is funded by a cooperative agreement with the USFDA and a matching grant from the Science Foundation Arizona.

Conclusion:

It took 90 years to accept the cause of this memory erasing, attitude destroying and human dignity stealing deadly disease that was first discovered in a mental asylum by Dr. Alois Alzheimer.

Thereafter, discovering a safe an effective medicine for the treatment of Alzheimer’s disease has rather been very slow, if not frustrating, especially for the afflicted patients and their families. Some global pharma majors have even announced jettisoning research initiatives in this area.

Even with the application of modern day’s cutting edge science and technology, it is still difficult to fathom, how many years would still remain in waiting for a breakthrough treatment option for Alzheimer’s disease.

In a scenario like this, even today, the very thought of becoming a victim of this life-threatening disease sends shivers down the spine of many.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

 

 

Alzheimer’s Disease: Robs Memory: Steals Dignity: Escapes Treatment

At a well reputed Mumbai Club, quite unexpectedIy, I bumped into Sumeet (name changed). It has indeed been a long while since we met at his home in South Mumbai. He came there with his wife Shilpa (name changed). Sumeet, was literally an icon of yesteryears in every respect, a bright engineer with MBA and a much-accomplished leader of his time who retired at the turn of the new millennium.

“How are you Sumeet da?”, I started off cheerfully, as he was looking all around.

“Very well, very well and you?”, he replied softly with a faint quivering of his lips, but without any eye contact.

“I am good Sumeet da, but have you recognized me?” I queried with apprehension.

Turning his face towards Shilpa, Sumeet hesitatingly replied, “No. But have we met before?”

The innocent question struck me as lightning from nowhere, making me a bundle of emotion momentarily. With a lump in my throat and clenching my fists, I struggled hard to regain my composure.

Sumeet, one of the the brightest of brights, from earlier years of our generation, is now a victim of a dreaded illness called Alzheimer’s Disease (AD). The disease has robbed him of his priceless memory, changed his behavior beyond recognition, kidnapped him from his own self, and has stolen most of his much-valued dignity in life, mercilessly.

Alzheimer’s Disease (AD) in brief:

Alzheimer’s Disease (AD), as known to many, is the most common form of dementia, accounting for 60 to 80 percent of all cases, that results in serious memory loss and other intellectual and behavioral traits of individuals, serious enough to interfere with a person’s daily life and tasks.

AD has been defined as, a neurodegenerative type of dementia, in which the death of brain cells causes memory loss and cognitive decline. The total brain size shrinks with AD, as the tissue has progressively fewer nerve cells and connections. Brains affected by AD would always show tiny inclusions in the nerve tissue, called plaques and tangles.

Plaques are found between the dying cells in the brain – from the build-up of a protein called beta-amyloid, while the tangles are within the brain neurons and from a disintegration of another protein, called tau.

Though the abnormal protein clumps and inclusions in the brain tissues are always present in AD, there could be another underlying process also that is actually causing the disease, which scientists are not sure of, as yet.

Be that as it may, with the progression of the disease, besides memory loss, AD precipitates other serious symptoms, such as, deepening confusion about events, time and place; mood and behavior changes; unfounded suspicions about family, friends and even professional caregivers; disorientation; other behavior changes; then difficulty speaking, swallowing and walking. At a late stage, the patients lose the ability to carry on even a conversation and respond to their environment.

Cause:

Although the causes of AD are not quite clear to the scientists, as yet, the disease results from a combination of genetic, lifestyle and environmental factors that adversely affect the brain over a period of time.

Scientists opine that in less than 5 percent of the cases, the causative factors of the AD are specific genetic changes that can almost definitively indicate that a person would develop AD. According to published reports, while the strongest risk gene found so far is apolipoprotein e4 (APOE e4), other risk genes have not been conclusively confirmed, just yet.

Survival rate:

According to published reports, the survival rate of AD patients, after their symptoms become noticeable to others, can range from 4 to 20 years, depending on health conditions, the average being 8 years. In the United States, AD is the sixth leading cause of death.

Not a normal part of the aging process:

Although majority of people with AD are over 60 years of age, it is not just a disease of old age. Up to 5 percent of cases the disease may strike even younger people in 40s or 50s. Women are found to be more prone to AD than men.

Prevalence:

The World Health Organization (WHO) declared dementia, in general, as a priority condition in 2008, through the Mental Health Gap Action Program.

Each year, the total number of new cases of dementia worldwide has been reported as nearly 7.7 million, which means one new case every four seconds.

According to AC Immune SA of Switzerland, AD will be one of the biggest burdens of the future society showing dramatic incidence rates. Over 44 million people were now affected with AD worldwide. Since the incidence and prevalence of AD increase with age, the number of patients will grow dramatically as our society gets older. By 2050 the patient numbers are expected to triple, touching 135 million AD patients worldwide.

India:

According to another report titled, “Priority Medicines for Europe and the World – A Public Health Approach to Innovation” By Béatrice Duthey, Ph.D published on 20 February 2013, the fastest growth of AD in the elderly population is now taking place in China, India, and their south Asian and western Pacific neighbors and has become a major public health concern as the population ages.

AD is the most common kind neurodegenerative disease in India. There are reportedly around 5 million dementia patients in the country of which, roughly 70 to 80 per cent have AD. This number is expected to double by 2030, and the costs involved are expected to increase three times. Besides drugs, costs of ‘care giving’ for AD patients are also expected to rise significantly.

The market and economic impact:

According to AC Immune SA, AD market is currently estimated at US$ 5 billion annually and is expected to exceed US$ 20 billion by 2020.

The global economic impact of AD is shown by its worldwide cost of US$ 640 billion, exceeding 1 percent of gross world product. It can be seen as the most significant health crisis in the 21st century. The 2010 annual costs of treating and caring for patients was  $183 billion in the US alone. This figure is expected to increase to $ 1.1 trillion in 2015.

AD is becoming the third most expensive disease, counting for 30 percent of the US healthcare costs. The medical costs for Alzheimer´s Disease patients are three times higher than for other older patients. Moreover, AD patients mostly live at home resulting in high impact on family’s health, emotional well being, as well as their employment and financial security.

India:

Many elderly people in India live with AD without any treatment, accepting the condition as an unavoidable one and related to the aging process of an individual.

The present day costs of maintaining a patient with AD in India, who has been diagnosed, are reportedly any where between Rs. 50,000 to Rs. 4,50,000. Additionally, many elderly couples are just not frail and living alone these days, as their children may be working in a far off country.

Currently, AD market in India is reportedly around US$ 50 million, growing around 25 percent. More disease awareness initiatives are expected to accelerate the market growth by manifold. Sun Pharma is the market leader in the AD segment. Other, key players are Dr. Reddy’s Laboratories (DRL), Torrent, Glenmark, Ranbaxy, Cipla and Alkem

In fact, Cipla recently reportedly announced an investment of US$ 21 million in Chase Pharmaceuticals of the United States, which is an early-stage drug development company focused on developing novel approaches to improve treatments for Alzheimer’s disease.

In addition, DRL is also making rapid strides in this area. In 2013, the company launched generic Donepezil Hydrochloride tablets for AD in the US market.

Treatment:

There is no cure for AD as of date. There is no disease-modifying treatment for AD even in the global market, either.

Since 2003, there has not been any single innovative drug launched in the global market either for prevention or cure of AD. The available drugs cannot stop the progression of the disease. They just temporarily slow the worsening of dementia symptoms. The situation gets even more complicated as the disease is usually diagnosed late, when already 70 percent of the nerve cells in the brain are dead.

Global researchers are looking for new treatments to alter the course of the disease and improve the quality of life for people suffering from this dreaded disease.

For the treatment of AD, the U.S. Food and Drug Administration (FDA) has approved two types of medications, namely,

-      Cholinesterase inhibitors, such as, Aricept, Exelon, Razadyne, Cognex

-      Memantine, such as, Namenda to treat the cognitive symptoms (memory loss, confusion, and problems with thinking and reasoning) of the disease.

Many doctors prescribe both types of medications together, along with Vitamin E for cognitive changes.

However, Aricept is the only cholinesterase inhibitor approved to treat all stages of AD, from moderate to severe.

Although, Tacrine (Cognex) was the first cholinesterase inhibitor approved, very few doctors prescribe this drug today because of more serious side effects.

According to The Alzheimer’s Association, the world’s leading voluntary health organization in Alzheimer’s care, support and research; the current treatments for AD at a glance are as follows:

Treatments at a glance:

Generic Brand Approved For Side Effects
donepezil Aricept (Eisai/Pfizer) All stages Nausea, vomiting, loss of appetite and increased frequency of bowel movements.
galantamine Razadyne (Janssen) Mild to moderate Nausea, vomiting, loss of appetite and increased frequency of bowel movements.
memantine Namenda/Ebixa (Actavis/Lundbeck) Moderate to severe Headache, constipation, confusion and dizziness.
rivastigmine Exelon (Novartis) Mild to moderate Nausea, vomiting, loss of appetite and increased frequency of bowel movements.
tacrine Cognex (Pfizer) Mild to moderate Possible liver damage, nausea, and vomiting.
vitamin E Not applicable Not approved Can interact with antioxidants and medications prescribed to lower cholesterol or prevent blood clots; may slightly increase risk of death.

India:

In India the treatment is much the same. Besides, patented versions, relatively cheaper generic equivalents of all these drugs are available in the country.

On going drug trials: 

As there are no effective therapies for AD, this therapy segment remains at the top of the list for unmet needs, globally. Disease-modifying therapies could transform this market appreciably.

At the Alzheimer’s Association International Conference held in Copenhagen, Denmark from July 12 to 17, 2014, scientists described five trials that may prevent the onset of the neurodegenerative disease in people not yet experiencing cognitive decline, as follows:

  • Gantenerumab and Solanezumab: Two experimental drugs, , both of which are antibodies designed to bind to amyloid and prevent it from forming brain-damaging plaques.
  • Solanezumab: An experimental anti-amyloid compound.
  • The trial will first pilot a screening test for two genes to see if it can accurately predict risk of mild cognitive impairment. The next phase of the trial will test an experimental compound designed to delay symptoms of mild cognitive impairment and Alzheimer’s disease in people without symptoms.
  •  Crenezumab: Anti-amyloid antibody
  •  An immunotherapy that prompts the body’s immune system to produce antibodies against amyloid protein, and a beta-secretase inhibitor that blocks the production of certain forms of amyloid.

According to Alzheimer’s Disease Therapeutics and Diagnostics: World Market 2013-2023 the following global players hold greatest potential. In particular, the analysis investigates these companies:

• Pfizer
• Eisai
• Actavis
• Lundbeck
• Novartis
• TauRx Therapeutics
• AC Immune.

A large pharma industry association of the United States has indicated in a report that dedicated researchers are currently working on nearly 100 medicines in development for Alzheimer’s and other dementias. These could give future patients a new hope for a future free of AD.

Conclusion:

AD can strike anyone at any time without any visible warning whatsoever. It then robs the person’s memory, steals the individual’s dignity of life, evades all available current treatments, till it is able to extinguish slowly and agonizingly the last flicker of life, mostly much sooner than otherwise it would have been.

Like many other countries, India – the world’s 2nd largest population, is also facing a crisis in dealing with the growing number of AD patients.

These patients require constant support from family/professional caregivers along with medical attention. The progression of the disease leaves patients mostly in semi-vegetative states, at times for years.

If no cure is available for AD, arresting the disease progression becomes a major health challenge in the country. Currently only short term symptomatic treatment is available. Neither is there any organized mechanism for early diagnosis of AD with specific markers, which could lead to early intervention with the most appropriate and effective drugs to address the disease sooner.

Alzheimer’s Disease that turns millions of otherwise boisterous individuals, like Sumeet, into living dead, snatching away everything that a life would possibly demand at its minimum, must feature in the areas of focus of the new national heath policy of India under the new dispensation.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.