by Emerging social problems or opportunities can significantly affect the funding available to develop medicines for certain diseases. When COVID-19 raged around the world, funding from Operation Warp Speed allowed a vaccine to be developed in record time. Public awareness campaigns, such as the ALS Ice Bucket Challenge, can also raise money directly for research. This viral social media campaign provided 237 scientists with nearly $90 million in research funding between 2014 and 2018, leading to the discovery of five genes linked to amyotrophic lateral sclerosis, commonly called Lou Gehrig’s disease, and new trials. clinical.
How science approaches drug development
To create innovative treatments, researchers need a basic understanding of which pathological processes they need to improve or block. This requires developing cellular and animal models that can simulate human biology.
It can take many years to examine potential treatments and develop the finished drug, ready to be tested in people. Once scientists identify a potential biological target for a drug, they use high-throughput screening tests to rapidly screen hundreds of chemical compounds that may have a desired effect on the target. They then modify the most promising compounds to improve their effects or reduce their toxicity.
When these compounds have mediocre results in the laboratory, companies are likely to stop their development if the estimated potential revenue from the drug is less than the estimated cost to improve treatments. Companies can charge more money for drugs that dramatically reduce death or disability than for those that only reduce symptoms. And researchers are more likely to continue working on drugs that have greater potential to help patients. To gain FDA approval, companies must ultimately demonstrate that the drug causes more benefit than harm to patients.
Sometimes researchers know a lot about a disease, but the technology available is insufficient to produce a successful drug. Scientists have long known that sickle cell anemia is the result of a defective gene that causes bone marrow cells to produce malformed red blood cells, causing severe pain and blood clots. Scientists lacked a way to solve the problem or solve it with existing methods.
However, in the early 1990s, basic scientists discovered that bacterial cells have a mechanism for identifying and editing DNA. With that model, researchers began hard work developing a technology called CRISPR to identify and edit genetic sequences in human DNA.
The 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 anemia was a big target for this technology because it was caused by a single genetic problem. It was also an attractive disease to focus on because it affects about 100,000 people in the United States and is costly to society, causing many hospitalizations and lost days of work. It also disproportionately affects African Americans, a population that has been underrepresented in medical research.
Drug development in the real world
To put all of these aspects of drug development into perspective, let’s consider the leading cause of death in the United States: cardiovascular disease. Although there are several medication options available for this condition, there is an ongoing need for more effective and less toxic medications that reduce the risk of heart attacks and strokes.
In 1989, epidemiologists discovered that patients with higher levels of bad cholesterol, or LDL, suffered more heart attacks and strokes than those with lower levels. Currently, 86 million American adults have high cholesterol levels that can be treated with medications, such as the popular statins Lipitor (atorvastatin) or Crestor (rosuvastatin). However, statins alone cannot get everyone to reach their cholesterol goals, and many patients develop unwanted symptoms that limit the dose they can receive.
So scientists developed models to understand how LDL cholesterol is created and eliminated in the body. They found that LDL receptors in the liver removed 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 prevent it from working. Another drug, Leqvio (inclisiran), blocks the genetic material that codes 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 highly prevalent diseases with devastating social consequences, such as Alzheimer’s disease and opioid use disorder. But the work of foundations and advocacy groups can improve research funding for other specific diseases and conditions. Policies like the Orphan Drug Act also create successful incentives for discovering treatments for rare diseases.
However, in 2021, 51% of US drug discovery spending went to just 2% of the population. How to strike a balance between offering incentives to develop miracle drug therapies for a few people at the expense of the many is a question that researchers and policymakers are still grappling with.
This article is republished from The Conversation, an independent, nonprofit news organization bringing you data and analysis to help you understand our complex world.
It was written by: C. Michael White, University of Connecticut.
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C. Michael White does not work for, consult with, own shares in, or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond his academic appointment.
