Over several decades, in fact, since its very inception, pharma R&D has been playing a crucial role in alleviating diseases of various types – from severe acute infections, to a large variety of non-infectious chronic illnesses, including many dreaded diseases, such as, cancer.
In the battle against diseases, pharma research and development initiatives, both by a large number of academia and also the pharma players, have mostly won, decisively. R&D has been consistently coming out with flying colors, both in finding cures and also in effective disease management, to prolong and improve the quality of life of billions of people, the world over.
However, there is still an important disease area, where pharma R&D has not been successful yet. Without any prior warning, this disease stealthily affects the human brain and completely erases the entire lifetime memory of the person, gradually but surely, over a relatively short period of time. This disease is known as Alzheimer’s, following the name of Dr. Dr. Alois Alzheimer, who first detected it in 1906. Due to its devastating impact on human memory, some, very appropriately, term the Alzheimer’s disease – ‘The memory thief’.
I discussed this subject in one of my previous articles titled, “It Took 90 Years To Accept The Dreaded Disease Discovered In A Mental Asylum”, published in this Blog on December 01, 2014.
A recent alarm for a future epidemic:
A January 6, 2016 paper titled, “Sounding the alarm on a future epidemic: Alzheimer’s disease”, published by the well reputed public research university in the United States, ‘The University of California, Los Angeles (UCLA), made the following noteworthy observation:
“If the aging trend illustrates the success of public health strategies, it also raises the specter of a major public health crisis – a sharp rise in the number of people living with Alzheimer’s disease.”
Causing havoc in many lives and families:
‘Alzheimer’s Disease Education and Referral (ADEAR) Center’ of the United States, currently ranked Alzheimer’s disease as the sixth leading cause of death in the United States, but recent estimates indicate that the disorder may rank third, just behind heart disease and cancer, as a cause of death for older people.
According to Mayo Clinic, the frightful disease – Alzheimer’s, is progressive in nature. At the onset, the afflicted persons may exhibit just mild confusion and some difficulty in remembering.
Tragically, in around five years or a little after, Alzheimer’s would erase the entire lifetime memory of most of the affected persons, when they may even forget the important people in their lives and undergo dramatic personality changes.
The dreaded disease – Alzheimer’s, still without any effective medication in place, has been causing havocs in many lives and families since long, involving many great international personalities too. It is one of those ailments, where the disease process mostly commences almost a decade before the visible appearance of above clinical symptoms.
Worldwide Projections of Alzheimer’s Disease Prevalence:
The above UCLA report highlights the worldwide projections of Alzheimer’s disease prevalence from 2005 to 2050, which includes both the early and late stage patients.
According to this report, the number of people afflicted by this total memory-erasing disease, would grow from 35.26 million in 2015 to as high as 106.23 million populations in 2050, as follows:
|Year||Alzheimer’s disease prevalence (in Millions)|
Similar situation in India:
The situation in India seems to be no different, though we are living today in the midst of the hype of ‘Demographic Dividend’.
According to the March 2012 report of ‘The Population Reference Bureau’ of Washington DC of the United States, India’s population with ages 60 and older, who are more prone to Alzheimer’s disease, is projected to increase dramatically over the next four decades, from 8 percent in 2010 to 19 percent in 2050. By mid-century, this age group is expected to encompass 323 million people, a number greater than the total US population in 2012.
Currently available treatment:
At present, there are no treatments available that can stop or slow down the progression of Alzheimer’s disease in the brain of the affected persons.
As I wrote earlier, very often the onset of this disease starts decades before the visible manifestation of even preliminary symptoms. Thus, there is a critical need for early medical interventions to arrest the disease progression.
Again, quoting Mayo Clinic, current Alzheimer’s disease medications and management strategies may at best temporarily improve symptoms. These symptomatic treatments can sometimes, help Alzheimer’s patients maximize cognitive and other related functions to the extent possible, and thereby maintain independence for a little while longer.
Many earlier research had postulated that plaques and tangles are primarily responsible for the permanent damage and destruction of nerve cells.
While the plaques are abnormal clusters of beta-amyloid protein fragments between nerve cells, tangles are twisted fibers made primarily of a protein called “tau” that accumulates in the brain cells, damaging and killing them.
The appearance of these two in the brain structure makes the affected persons suffer from almost irreversible memory loss, altered thinking pattern and associated behavioral changes, which are usually serious in nature.
However, I shall discuss below about a very recent research that is focusing on a different and novel target.
Key hurdles in Alzheimer’s drug development:
Despite all these, almost at a regular interval, we have been getting to know about various new studies on Alzheimer’s disease, mostly from academic and scientific institutions. It clearly vindicates, at least, the global academia and also some pharma players, are working hard to get an effective key to unlock the pathway of Alzheimer’s disease process.
The hurdles in developing a suitable drug for effective treatment of Alzheimer’s disease are many. A paper titled, “Researching Alzheimer’s Medicines: Setbacks and Stepping Stones Summer 2015”, published by the Pharmaceutical Research and Manufacturers of America (PhRMA) – a trade association of leading biopharmaceutical researchers and biotechnology companies of the United States, cited the following three major reasons as examples:
- Scientists still do not understand the underlying causes and mechanisms of the disease. It remains unknown whether many of the defining molecular characteristics of the disease are causes, effects, or signs of progression. This scientific knowledge gap makes the identification and selection of viable targets for new medicines difficult.
- Current preclinical models of Alzheimer’s disease are limited in the extent to which they can be extrapolated or translated to the human condition. Better models are needed to facilitate preclinical testing of drug candidates and better predict the effects of the drug in humans.
- The absence of validated, non-invasive biomarkers to identify disease presence and progression means the diagnosis is delayed until an individual becomes symptomatic. This makes it particularly challenging to evaluate, enroll, retain, and follow up with patients in clinical studies. It also makes it challenging to assess the effects of the drug candidate. Ultimately, this leads to long and very expensive clinical trials.
The PhRMA publication also states that “researchers believe that no single medicine will be able to defeat Alzheimer’s; rather, several medicines will probably be needed to combat the disease. Thus, researchers need not one, but an array of options to prevent or treat Alzheimer’s disease.”
High rate of R&D failure, with flickers of success:
The above PhRMA publication also indicates, between 1998 and 2014, 123 medicines in clinical development have been halted and have not received regulatory approval.
In this rather gloomy R&D scenario, there are also some flickers of success in this pursuit.
In a recent study, the scientists at the University of Southampton announced that their findings added weight to evidence that inflammation in the brain is what drives the disease. A drug, used to block the production of these microglia cells in the brains of mice, had a positive effect. The study, therefore, concluded that blocking the production of new immune cells in the brain could reduce memory problems seen in Alzheimer’s disease. This finding is expected to pave the way for a new line of treatment for Alzheimer’s disease.
Currently, most drugs used for the treatment of dementia targeted amyloid plaques in the brain, which are considered as a key characteristic of people with the Alzheimer’s disease. According to an article published in Forbes on March 20, 2015, several amyloid-clearing drugs have failed to show statistically significant benefits in large clinical trials. Notable among those are Bapineuzumab – developed by Elan Pharmaceuticals, Pfizer and Johnson & Johnson failed in 2009; Solanezumab of Eli Lilly failed in 2012; and so did Gantenerumab of Roche in 2014.
The latest study, as quoted above, published in the journal ‘Brain’, on January 8, 2016 suggests that targeting inflammation in the brain, caused by a build-up of immune cells called microglia, could halt progression of the disease.
Another flicker of hope is, another drug being developed by Biogen Idec for the treatment of Alzheimer’s disease appeared to slow down the inexorable cognitive decline of patients’, though in a small and a preliminary study.
Lack of research funding is a critical impediment:
Be that as it may, many experts believe that not enough is still being done in Alzheimer’s research, especially in the area of funding.
“Dementia is the biggest health and social care challenge of our generation, but research into the condition has been hugely underfunded. This lack of funding has hampered progress and also restricted the number of scientists and clinicians working in the dementia field.”
As an illustration, MNT mentioned that in the United States Alzheimer’s research received US$504 million in funding from the National Institutes of Health (NIH) in 2014, while cancer received more than US$5 billion. Breast cancer alone received more funding than Alzheimer’s at US$674 million.
Quoting an expert in this field the report highlighted, “Other diseases have demonstrated that sustained investment in research can improve lives, reduce death rates and ultimately produce effective treatments and preventions. We have the tools and the talent to achieve breakthroughs in Alzheimer’s disease, but we need the resources to make this a reality.”
From the published research reports, it appears that the quest to decipher the complicated Alzheimer’s disease process continues, at least by the academic and scientific institutions, with equal zest.
These scientists remain committed to finding out the ‘magic bullet’, which would be able to effectively address the crippling disease. As a result, the research has also moved from discovery of effective amyloid-clearing drugs to search for new molecules that targets inflammation in the brain, caused by a build-up of immune cells called microglia.
Undeniably, the challenges ahead are still too many.
Nevertheless, enough confidence is also building up to halt the epidemic of Alzheimer’s by overcoming those hurdles, the world over. Experts are hoping that both a cure and also successful preventive measures for the disease, are not too far anymore.
Though some Global Pharma majors invested significantly to discover effective drugs for Alzheimer’s disease, overall research funding in this area is still far from adequate, according to the Alzheimer’s Society.
For various reasons, not many pharma players today seem to believe that it would be financially prudent for them to make significant investments in developing new molecules for the treatment of Alzheimer’s – the disease that robs memory of millions of people, completely, and without any prior warning whatsoever.
‘The Memory Thief’ continues to prowl, undeterred, still eluding otherwise brilliant Pharma R&D, across the world.
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.