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.
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.
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.
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.
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.
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.
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.|
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:
• 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.
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.