A headline about a substance showing promise against Alzheimer’s disease or depression can leave you wondering what researchers have shown and what remains untested.
Before a doctor can prescribe a new medicine, researchers must investigate both what a substance does and how the body handles it. For a candidate intended to act in the brain, they also need to find out whether it reaches its target. Those early findings cannot establish whether patients will benefit.
Key takeaways
- An effect in cells or animals does not establish that a candidate will help people.
- Reaching the brain is a separate research question because of the blood-brain barrier.
- Studies in people test whether a candidate helps patients, and safety monitoring continues after approval.
The journey from an idea to a treatment
One part of how new medicines are developed is starting with a substance that has an effect in a laboratory model, such as blocking a protein. At this stage, it is a candidate for further investigation. The US Food and Drug Administration (FDA) describes early development as a time when researchers investigate how a candidate is absorbed, distributed, metabolised and excreted, alongside what it does.
Preclinical research uses laboratory models and can include animal studies. In the FDA’s outline of medicine development, researchers review these findings and decide whether the candidate should be tested in people. Progression is not automatic.
Some laboratory work uses brain organoids, which are tiny 3D cell models grown from stem cells. Brain organoid research has helped scientists study how certain genetic variations linked to autism affect brain development. Organoids are simplified models, not replicas of a human brain. Findings from them cannot establish that a treatment will work in patients.
Clinical research means studies in people. In the FDA’s consumer explanation, Phase 1 trials emphasise safety, while Phase 2 trials emphasise effectiveness. Early safety findings alone therefore cannot establish that a candidate treats a disorder.
In the US, the FDA review team examines the submitted evidence and decides whether to approve the application. Approval does not mean a medicine has no risks. Safety monitoring continues after approval in both the US and the EU.
Why reaching the brain is a separate challenge
The blood-brain barrier helps protect the brain. The US National Cancer Institute defines it as a network of blood vessels and tissue made up of closely spaced cells that helps keep harmful substances from reaching the brain. Researchers must investigate whether a candidate intended to act in the brain can cross this barrier.
Drug metabolism and pharmacokinetics, shortened to DMPK, helps researchers investigate a compound’s behaviour in the body. The US National Institute of General Medical Sciences defines pharmacokinetics as the study of how the body acts on a medicine. This includes four processes, often abbreviated as ADME.
- Absorption: Getting into the bloodstream. For a medicine taken by mouth, how much of the dose reaches the blood?
- Distribution: Travelling to tissues. Where does the compound go once in the blood, and how much reaches the brain?
- Metabolism: Being chemically changed. How do the liver and other tissues change the compound, and what substances result?
- Excretion: Leaving the body. How quickly are the compound and its breakdown products removed, often through the kidneys into urine?
Finding a compound in the blood does not show that useful amounts reach a brain target. For example, Viva Biotech’s DMPK CRO services include blood-brain barrier penetration studies, with brain and cerebrospinal fluid measurements, alongside in vivo pharmacokinetic studies.
Even when a compound reaches its target, it may fail to change a disease. Measurements of where it travels and how long it remains help researchers assess a candidate, but evidence of benefit for patients requires studies in people.
What outside research teams contribute
A contract research organisation (CRO) is an outside team that performs agreed research tasks for a company or academic group developing a compound. These tasks can include measuring how quickly a compound breaks down, where it travels in the body and whether it interacts with other medicines.
As a commercial example, the same provider lists metabolic-stability, permeability and drug-interaction tests among its outsourced DMPK services. These investigate how readily a compound is chemically changed, crosses biological barriers and may interact with other medicines. The published service list describes the research offered, rather than results for any particular candidate.
Consider a hypothetical compound that reduces a damaging process in brain cells grown in a dish. If researchers intend it to be taken by mouth, they need to investigate how well it is absorbed and how quickly the body changes or removes it. They also need to examine whether it reaches brain tissue and could interact with other medicines. Each test answers a specific question that the cell experiment leaves open.
Distribution and pharmacokinetic studies address where a compound travels and how its levels change over time. Researchers can use these findings alongside other preclinical evidence to decide whether to continue development, modify the molecule or stop the programme.
A contract laboratory contributes evidence to those decisions. In the US, the FDA’s review team makes the approval decision after examining the submitted development data.
Takeaway
Lab testing helps researchers decide what to investigate next, but each result has limits. A candidate’s movement through the body and arrival at brain tissue are different questions from whether it improves symptoms. Preclinical findings can guide clinical studies, while evidence from people and ongoing safety monitoring are needed before and after approval.
FAQs
- Does a promising laboratory result mean a treatment is ready? No. A result in cells or animals describes what happened under those experimental conditions. Studies in people are needed to investigate whether the candidate benefits patients and what risks it carries.
- Why might researchers stop work on a candidate? Preclinical findings may reveal poor absorption, rapid breakdown, failure to reach the target or safety concerns. Researchers review this evidence before deciding whether testing in people is warranted.
- Can early tests identify every possible side effect? No. The FDA states that no drug is absolutely safe and that complete safety information is impossible at the time of approval. Safety monitoring must continue as more people take a medicine.
- What happens after a treatment is approved? In the EU pathway described by the European Medicines Agency (EMA), the agency and national authorities continue monitoring a medicine’s safety after authorisation. The FDA also runs post-market safety monitoring in the US.
