Alzheimer’s disease – not cracking the nut (yet)

As an anthropologist, market researcher and consultant working with pharmaceutical companies, I follow trends in the medical field. Neuroscience is one of the areas on the rise. Expecting this field to accelerate in terms of drug development, I compiled a comprehensive database of Canadian neurologists and started engaging this audience. Alzheimer’s disease specifically is an area of great unmet need where a massive market is ripe for innovations, pharmacological and otherwise. I recently surveyed neurologists to better understand their perspectives. You can read the results here: https://creativeresearchdesigns.com/examples-of-work

Neuroscience has received significant investment in the past decade.

In the U.S., President Obama launched the Brain Initiative in 2013 with a $100 million US dollar investment. He said: “Today, our scientists are mapping the human brain to unlock the answers to Alzheimer’s… Now is not the time to gut these job-creating investments in science and innovation. Now is the time to reach a level of research and development not seen since the height of the Space Race.”1

A similar investment was made in Canada with the establishment of the Brain Research Fund in 2011, a public-private partnership between Brain Canada and Health Canada. Its website describes the purpose of the investment as follows: “This visionary commitment by the federal government will ensure that Canada continues to be among the leaders in the global challenge to understand brain function and brain diseases.”2 Regional and local initiatives abound.3

However, while research funding is available, many worthwhile initiatives are competing for it.

Brain science is a diverse field; and neurologists often specialize in a particular area.

When I researched Canadian neurologists and potential participants for my Alzheimer’s survey, I noticed that only a subset of neurologists deals with Alzheimer’s and other dementias. Other significant specializations include multiple sclerosis, epilepsy, neuromuscular disorders, movement disorders (incl. Parkinson’s), migraine/ headache and stroke. The patient populations affected by these conditions are quite diverse, with epilepsy, MS, and migraine often affecting younger individuals and dementia, Parkinson’s and stroke primarily being diseases of the elderly.

While there are currently just over a thousand neurologists in Canada,4 only a subset of these would be relevant to a pharmaceutical company marketing a specific neurology drug.   

Many pharmaceutical companies have ventured into the area of neuroscience. According to the website Statistica, the top selling neurological drug products (2016 in the U.S.) are multiple sclerosis treatments, followed by medications for schizophrenia and bipolar disorder.5 Disease onset is typically younger for these conditions, impairment of day-to-day functioning can be significant, and patients remain on treatment for decades. Thus, they present interesting opportunities for pharmaceutical development.

Alzheimer’s disease is overdue for breakthrough discoveries.

But neurological diseases of the elderly have also received significant attention. Alzheimer’s disease, in particular, has proven to be a hard nut to crack. The last new treatment (Ebixa/memantine) came to Canada in 2005, joining the three cholinesterase inhibitors Aricept (donepezil), Exelon (rivastigmine) and Reminyl (galantamine). Neither of these agents are particularly effective in slowing down the progression of the disease. 

Many companies have tried to tackle the challenge of Alzheimer’s disease. Up until now, the path to a brighter future has been littered with unsuccessful clinical trials.6 Just this year, another five major flops joined the long list of previous attempts: Roche/AC Immune’s anti-tau antibody semorinemab, AbbVie/Voyager Therapeutics’ gene therapies, Sanofi/Denali’s RIPK1 inhibitor DNL747, and Eli Lilly’s and Roche’s amyloid antibodies solanezumab and gantenerumab. Biogen’s monoclonal antibody aducanumab is still in the running, but it faces an uphill battle to secure approval.

Will large pharma turn away, and leave the field to small, pre-clinical research companies for the time being? I believe there is reason for optimism about the future of brain research and the development of Alzheimer’s drugs specifically. Public attention and government incentives will continue to stimulate research. According to a recent article, 121 agents were in clinical trials for the treatment of Alzheimer’s disease at the beginning of 2020 (in ClinicalTrials.gov).7 Some are sponsored by large pharma and some by small start-ups. Even if beta-amyloid and tau protein turn out to be less promising drug targets than previously thought, with continued investment in this field, scientists are bound to come up with something eventually.

Non-pharmacological interventions deserve attention in Alzheimer’s.

In my survey among Canadian neurologists, one of the results that I found most interesting was their recognition of the importance of non-pharmacological measures.

Unprompted, Canadian neurologists identified supporting families, caregivers and home care as one of the top investment priorities to improve the lives of people with Alzheimer’s. When presented with a list of possible investment priorities, neurologists again picked ‘improved funding for home care’ along with ‘research into new drug treatments’ as the top two. Increased funding for long-term care facilities was perceived as less important.

Staying at home is certainly preferrable to living in long-term care, particularly under the current circumstances of the pandemic, and specific non-pharmacological interventions have the potential to significantly increase quality of life for Alzheimer’s patients.

One finding that intrigues and delights me is the brain’s storage of musical memories and the effect of music on the brain. It has been shown that memories of music persist while names of loved ones may already be fading into the background. The stimulation of those memories, and the participation in the making of music, can fill those affected by Alzheimer’s with great joy.

One of the projects supported by the Alzheimer’s Society of Canada is Voices in Motion, an intergenerational choir that brings together people with Alzheimer’s disease, caregivers and high school students.8 It combines the joyful act of singing with physical movement and social interaction. Based on findings from this study, researcher Dr. Debra Sheets, Associate Professor in the School of Nursing in Victoria, BC, will create a toolkit of best practices that can be used by other organizations who are interested in starting a community choir for people with dementia.

Early detection and screening are important, and AI may have a role to play in it.

For Alzheimer’s disease as well as for other areas of health, accurate and early diagnosis plays an important role in halting or slowing the disease before its effects become devastating. In fact, when my survey asked about top investment priorities, neurologists mentioned early detection and prevention unprompted. While there has been considerable research into biomarkers and brain imaging technology, more recently a number of companies have tried to harness the power of artificial intelligence for early detection of Alzheimer’s disease.

The Toronto startup Winterlight Labs uses AI to analyze speech patterns to detect cognitive impairment and other brain disorders.9 The company built a tablet-based assessment tool that is already being used in a clinical trial for an Alzheimer’s drug. Tech industry giant IBM, in conjunction with Pfizer, is working on something similar that presumably can predict onset of Alzheimer’s with 71% accuracy.10 Researchers at the Boston School of Medicine have developed a computer algorithm based on AI that can accurately predict the risk for and diagnose Alzheimer’s disease using a combination of MRI, testing to measure cognitive impairment, and data on age and gender.11

In Conclusion

Brain health is responsive to a variety of behavioural, technological and pharmacological interventions. Hopefully, research investments in Alzheimer’s will pay off in the not-so-distant future, and lead to breakthroughs that significantly improve the trajectory of this disease and the quality of life of those affected. I am keeping my fingers crossed.

1: https://obamawhitehouse.archives.gov/BRAIN; https://obamawhitehouse.archives.gov/the-press-office/2013/04/02/fact-sheet-brain-initiative

2: https://braincanada.ca/canada-brain-research-fund/

3: https://blog.braininstitute.ca/mental-health-is-brain-health-a-paradigm-shift/; http://www.camh.ca/en/driving-change/about-camh; https://www.uhn.ca/KNC; https://www.baycrest.org/; https://blog.mtl.org/en/montreal-leads-way-neuroscience-breakthroughs; https://www.mcgill.ca/neuro/

4: https://www.cma.ca/sites/default/files/pdf/Physician%20Data/01-physicians-by-specialty-province-e.pdf

5: https://www.statista.com/statistics/318259/revenue-of-top-20-neurology-products-in-the-us/

6: List of recently failed clinical trials in Alzheimer’s disease

Roche/AC Immune: https://www.fiercebiotech.com/biotech/roche-ac-immune-s-tau-blocking-drug-flops-alzheimer-s-as-biotech-s-shares-halved

AbbVie/Voyager Therapeutics: https://www.fiercebiotech.com/biotech/abbvie-cans-voyager-alzheimer-s-parkinson-s-gene-therapy-pacts

Sanofi/Denali: https://www.biospace.com/article/denali-and-sanofi-pause-alzheimer-s-trial-and-pivot-to-another-drug/

Eli Lilly and Roche: https://www.fiercebiotech.com/biotech/lilly-and-roche-s-antibodies-fail-late-phase-alzheimer-s-test

7: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12050

8: http://alzheimersocietyblog.ca/meet-researchers-debra-sheets-university-of-victoria/

9: https://winterlightlabs.com/

10: https://venturebeat.com/2020/10/22/ibm-and-pfizer-claim-ai-can-predict-alzheimers-onset-with-71-accuracy/

11: https://neurosciencenews.com/ai-alzheimers-16326/

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