Two Disorders Interfering with Research on Alzheimer’s Disease

Thirty years ago, scientists began to unravel the mystery of the cause of Alzheimer’s disease. This knowledge has brought about a time of great enthusiasm for scientists to develop new therapies to prevent Alzheimer’s disease or to significantly delay symptoms once they exist.

Despite the ongoing progress and new hope that some treatments currently in human trials will change the course of the disease, the first optimism of neuroscientists like me has been significantly softened by reality. rice field. Many treatments have been tested on sound scientific evidence and have been shown to be ineffective in humans with symptomatic Alzheimer’s disease.

The fight against Alzheimer’s disease, like the fight against cancer, does not win in a single glorious “fight”. Instead, I believe that gradual but transformative progress will ultimately lead to success. Unlike cancer, the scientific community does not yet have a “survivor story” to support our efforts. Realizing the reality of ending Alzheimer’s disease requires the cooperation of scientists, pharmaceutical companies, governments and society. Only by recognizing and confronting all the obstacles that impede the development of treatments for Alzheimer’s disease can we be confident that the fight will be successful.

As a medical scientist and director of the McKnight Brain Institute at the University of Florida, who began studying Alzheimer’s disease at the School of Medicine in the late 1980s, we thank you for the extent of our collective scientific progress. I have also come to the calm perception that translating these advances into actual treatments that make a difference to patients suffering from this catastrophic disease is a very complex issue, not just science. ..

There are two important unscientific obstacles that require coordinated efforts by scientists, the citizens involved, society, and our legislators to overcome them. Lack of funds and patent law.

Financing is still behind

Governments in industrialized countries recognize that research funding for Alzheimer’s disease and related dementia is inadequate. This lack of funding has received broader attention. In fact, Bill Gates recently publicly acknowledged the need for more funding and promised $ 50 million to study Alzheimer’s disease.

In the United States, the National Institutes of Health’s funding has increased from $ 503 million annually to $ 1.391 billion over the past five years, with an additional $ 400 million proposed in 2018.

For many, even $ 500 million a year may sound like a lot of money, but given that the current cost to American society from Alzheimer’s disease is about $ 200-250 billion a year, research The money spent on is a reduction in buckets. In addition, I believe this additional funding is appropriate and necessary compared to cancer funding (about $ 6 billion annually from NIH).

Advocates for Alzheimer’s disease and others estimate that the number of individuals suffering from dementia has nearly tripled from 5 million to 13.5 million as the number of long-lived Americans increases.

We’re on the right track, but if we can spend $ 6 billion a year on cancer, we may need to spend that much on dementia to make a difference.

Unrealized goals

One of the challenges in treating this disease is that the brain is full by the time a person shows symptoms of Alzheimer’s disease. Therefore, many research efforts are focusing on prevention.

It is known that more than 20 years before the onset of overt symptoms of dementia, the pathology that causes the disease (protein deposits called amyloid plaques and entanglement of neurofibrils) appears.

These gradually accumulate in the brain, with amyloid leading to abnormal entanglement conditions, which appear to be more closely associated with cognitive decline.

Therefore, if small molecule drugs, antibodies, and even gene therapy can prevent these deposits, they may be able to prevent Alzheimer’s disease. Many studies are underway, but no preventative therapy exists.

Lifestyle interventions such as exercise and “memory-enhancing” mind games have also been investigated as possible ways to stop or delay cognitive decline, but evidence that they actually change the underlying condition. There is little evidence of delaying the course of the disease. ..

I have seen too many people living the healthiest lifestyle, staying intellectually and socially active throughout their lives, and still developing Alzheimer’s disease. They are evidence of the need for treatments that actually alter the underlying pathological and biological processes of the disease.

Surprising obstacles

The major, barely-spoken block to testing and developing the best treatments for prevention is the current patent law.

The cost of conducting the definitive clinical trials needed to test even symptomatic treatment can exceed $ 1 billion, and the cost of preventive trials far exceeds that figure.

Prophylactic trials can take 5 to 10 years or more to get an answer as to whether a drug or intervention is working. Patent protection and market exclusivity may have expired or only a few years left before the drug is approved.

This severely limits the ability of the pharmaceutical sector to invest in preventive research for Alzheimer’s disease. Costs cannot be justified from a business perspective.

This poses a big dilemma. Researchers, and those we want to help, need private sector investment, but the private sector does not have a clear financial incentive to carry out these studies. Pharmaceutical company scientists risk billions of dollars to develop and test preventive therapies for Alzheimer’s disease if approved for use only after the patent that protects Alzheimer’s disease has expired. You can’t make a case. The company will never be able to recover development costs.

That is why our society needs a new financial model to develop preventative therapies that encourage the long-term risky investments needed. One model that can be considered is to allow regulators to grant market exclusivity for a period of time without patent protection, allowing businesses to increase the typical return on investment for “hit” therapies. is. This can be negotiated on a case-by-case basis using the ROI’s pre-specified formula.

bright future

Even when we are heading for the prevention of Alzheimer’s disease, researchers help those who are currently suffering from or may have the disease before developing effective preventative measures. We recognize that we must continue our efforts.

As a field, researchers are learning from our past mistakes. Our knowledge of illness is mercilessly increasing and our tools are better than ever.

In addition, the increase in funding is attracting new researchers with new ideas that have the potential to become game changers. I am optimistic that these advances will not only prevent Alzheimer’s disease, but will also make a difference in people with the disease in the future. In fact, we want to work together to change the glossary of Alzheimer’s disease and related dementia from the inevitable incurable to the preventable and curable.

This article is republished by Conversation, a source of independent, non-profit news, analysis, and commentary from academic experts under a Creative Commons license.