by Emerging social issues or opportunities can significantly affect the funding available to develop drugs for certain diseases. When COVID-19 swept the world, funding from Operation Warp Speed led to the development of vaccines in record time. Public awareness campaigns such as the ALS ice bucket challenge can raise money directly for research. This viral social media campaign provided 237 scientists with nearly US$90 million in research funding from 2014 to 2018, leading to the discovery of five genes associated with amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease, and new clinical trials.
How science approaches drug development
To create breakthrough treatments, researchers need a basic understanding of the disease processes they need to improve or block. This requires the development of cell and animal models that can simulate human biology.
It can take many years to vet potential treatments and develop the finished drug product ready for testing in humans. Once scientists identify a potential biological target for a drug, they use high-throughput screening to rapidly assess hundreds of chemical compounds that may have a desired effect on the target. They then modify the most promising compounds to enhance their effects or reduce their toxicity.
When these compounds have poor results in the laboratory, companies are likely to stop development if the estimated potential revenue from the drug is less than the estimated cost of improving the treatments. Companies can charge more money for drugs that significantly reduce death or disability than they charge for those that only reduce symptoms. And researchers are more likely to continue working on drugs that have greater potential to help patients. To get FDA approval, companies must ultimately show that the drug has more benefits for patients than harm.
Sometimes, researchers know a lot about a disease, but the technology available is not enough to produce a successful drug. For a long time, scientists have known that sickle cell disease is caused by a faulty gene that directs cells in the bone marrow to produce red blood cells poorly, causing severe pain and blood clots. Scientists had no way to solve or work around the issue with existing methods.
However, in the early 1990s, basic scientists discovered that bacterial cells have a mechanism to recognize and edit DNA. With that model, researchers began working hard to develop a technology called CRISPR to identify and edit genetic sequences in human DNA.
Technology eventually advanced to the point where scientists were able to successfully target the problematic gene in sickle cell patients and edit it to produce normally functioning red blood cells. In December 2023, Casgevy became the first CRISPR-based drug approved by the FDA.
Sickle cell disease made an ideal target for this technology because it was caused by a single genetic issue. It was also an attractive disease to focus on because it affects about 100,000 people in the US and is costly to society, resulting in many hospitalizations and lost work days. It also disproportionately affects Black Americans, an underrepresented population in medical research.
Drug development in the real world
To put all these pieces of drug development into perspective, consider the leading cause of death in the US: cardiovascular disease. Although there are several drug options available for this condition, there is a continuing need for more effective and less toxic drugs that reduce the risk of heart attacks and strokes.
In 1989, epidemiologists found that patients with higher levels of bad cholesterol, or LDL, had more heart attacks and strokes than those with lower levels. Currently, 86 million American adults have elevated cholesterol levels that can be treated with drugs, such as the common statins Lipitor (atorvastatin) or Crestor (rosuvastatin). However, statins alone cannot achieve their cholesterol goals for everyone, and many patients develop unwanted symptoms that limit the dose they can receive.
So scientists have developed models to understand how LDL cholesterol is created and removed in the body. They found that LDL receptors in the liver remove bad cholesterol from the blood, but a protein called PCSK9 destroys them prematurely, increasing bad cholesterol levels in the blood. This led to the development of the drugs Repathy (evolocumab) and Praluent (alirocumab) which bind to PCSK9 and stop it from working. Another drug, Leqvio (inclisiran), blocks the genetic material coding for PCSK9.
Researchers are also developing a CRISPR-based method to treat the disease more effectively.
The future of drug development
Drug development is driven by the priorities of their funders, whether governments, foundations or the pharmaceutical industry.
Based on the market, companies and researchers tend to study very widespread diseases with devastating societal consequences, such as Alzheimer’s disease and opioid use disorder. But the work of advocacy groups and foundations can improve research funding for other specific diseases and conditions. Policies like the Orphan Drug Act also create successful incentives to find treatments for rare diseases.
However, in 2021, 51% of drug discovery spending in the US was directed at just 2% of the population. a question that researchers and policy makers are still grappling with.
This article is republished from The Conversation, a non-profit, independent news organization that brings you facts and analysis to help you make sense of our complex world.
It was written by: C. Michael White, University of Connecticut.
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