Are We Forgetting to Develop Vaccines for Diseases other than COVID?

Don’t get me wrong, we are not overdoing it with COVID-19. The rollout of vaccines and generating herd immunity are desperately needed.

We all long for a return to pre-pandemic social life, free travel and safely hugging loved ones. Over a year of lockdowns and restrictions is having a serious impact on our mental health.

What I am asking is that we apply the same urgency to other devastating diseases.

Alzheimer’s disease, the most common form of dementia, is progressing silently. It is an insidious pandemic affecting over 6 million people in the US. It is not an infectious disease but as life expectancy is increasing, the social and economic burden on our health system and society is growing continuously: by 2050 the costs are predicted to rise to $1.1 trillion in the US.

Scientists are facing challenges that have slowed the development of a treatment. For one, the neurobiological mechanisms are complex. Brain proteins that execute essential functions in the healthy brain, start to misfold and form toxic deposits leading to neurodegeneration. Alzheimer’s hallmark proteins are amyloid-beta and Tau, but additional co-pathologies have been identified. The specific set of misfolded proteins varies between patients making it difficult to deliver the right treatment. Second, because of the variable onset and progression of the disease, the right moment to deliver a treatment is hard to predict. In most cases diagnosis happens late – too late – cognitive symptoms are detected once irreversible loss of neurons has taken place. In addition, various factors – gender, genetics, lifestyle, and education – influence who will suffer from Alzheimer’s and when it will start.

A focus on people living with Down syndrome could be the key to tackling Alzheimer’s. They are at increased genetic risk of developing Alzheimer’s due to an extra copy of chromosome 21 causing an overproduction of amyloid-beta. In fact, people living with Down syndrome make up the world’s largest population of individuals predisposed to getting Alzheimer’s.

Improvements in social integration and medical care have led to a dramatic increase in life expectancy in Down syndrome, from an average 25 years three decades ago, to 60 years today. This has exposed Alzheimer’s disease in Down syndrome and made it the main medical concern of the community. Indeed, it is unacceptable to lose these hard-earned years of life to dementia.

Trying to find an Alzheimer’s treatment for people living with Down syndrome seems costly and challenging as adequate tools need to be developed and validated for this specific population. But the body of literature on the topic has grown, thanks to pioneering studies on the genetics of Down syndrome and growing interest from researchers.

Today, we know that Alzheimer’s pathology can be detected in the early forties of people living with Down syndrome, about 2–3 decades earlier than in the general population, with first signs of mild cognitive impairment occurring around age 50 and dementia appearing around age 54.

Amyloid-beta increases at a rate that is twice as high in people living with Down syndrome compared to the general population and the cascade of events follows a specific, repeatable sequence: amyloid-beta increases first, then Tau becomes pathological before neurodegeneration kicks in and leads to functional loss. Knowing this time course could make it easier to predict the most effective time point to address Alzheimer’s in individuals with Down syndrome.

An active immunization strategy for Alzheimer’s consists of a vaccine designed to generate antibodies specifically targeting amyloid-beta, preventing its accumulation and boosting the clearance of the deposits. Based on the above, this approach would be most effective at early stages and might prevent the subsequent cascade of events.

The successful completion of the first clinical study evaluating an Alzheimer’s vaccine in individuals with Down syndrome has shown that vaccination is safe and can lead to the desired immune response and generate antibodies in people with Down syndrome.

Moving forward, we should continue to include genetic populations into clinical research and improve collaborations. They are highly motivated to contribute to research that aims to improving their life expectancy and quality of life. In addition, findings could be translated into strategies for a cure against Alzheimer’s disease in the broader population helping millions. The recent pledge by the National Institutes of Health to increase research funding in Down syndrome is certainly a step in the right direction, but we must all work together to ensure this momentum is not lost.

Vaccines have proved both their effectiveness in protecting us from infectious diseases and the power of global collaboration. Now, we must apply these lessons and develop new applications to overcome global health challenges beyond infectious diseases.

Dr. Andrea Pfeifer is Chief Executive Officer and co-founder of AC Immune SA. Dr. William Mobley is Distinguished Professor of Neurosciences at UC San Diego, where his laboratory studies the biology of Down syndrome, in particular the emergence of Alzheimer’s disease. He served as a site principal investigator in the recently completed AC Immune-sponsored vaccination trial in people with Down syndrome.