Your doctor tells you how many times a day you should take a pill, and whether to take it with or without food but they very rarely tell you the exact time at which it has to be taken. Chronopharmacology (also known as chronotherapy or circadian medicine) the idea that a pill popped at exactly the right time has maximum benefit could be a major influence on the future of medicine. Increasing studies are showing that what time of day we treat disease can be crucial, and that its possible to pinpoint the time of day when certain disease is at its worst.
In 1997, doctors in Denver split 59 asthmatics into three groups. The first group used steroid inhalers at 8am every day for four weeks. The second used the same inhalers, but much later in the day, at 5.30pm. The third group dosed four times a day at 7am, 12 noon, 7pm and 10pm at the time, this was believed to be the optimal regime.
After a month, the results were in. The 8am group saw the least improvement, while an inhaler at 5.30pm had similar efficacy to one used at regular intervals. In short, taking a drug once was just as effective as taking it four times, provided you took it at the right time of day.
Professor David Ray of the University of Oxford uses his own inhaler at the time when I think its going to be most effective (the exact time is his secret, as we have to be careful about single-person anecdotes). As co-director of the Sir Jules Thorn Sleep and Circadian Neuroscience Institute, the asthmatic professor has conducted his own research into body clocks and the respiratory disease. He also studies how matching medications with our circadian rhythms can improve the effectiveness of drugs.
Chronopharmacology is a field filled with jaw-dropping studies to whip out at the pub: in 2011, researchers at the University of Birmingham monitored people who had their influenza jabs in the morning versus those who had them in the afternoon. One month on, the patients who received their vaccination between 9am and 11am had higher levels of anti-flu antibodies than patients jabbed between 3pm and 5pm.
Our circadian rhythms are 24-hour cycles of biological activity that are regulated by our internal clocks along with external cues, such as light. You sleep at night not just because your mum told you to, but because when your retina detects light it inhibits the production of the hormone melatonin, stimulating wakefulness. Our body temperature varies by as much as half a degree throughout the day: usually, were coldest at 4am and hottest just in time for the News at Six. Our hormones, immune cells, and organ functions also fluctuate; mouse livers, for example, grow almost 50% in size during the day before shrinking at night.
Many chronobiologists (chrono is the Greek word for time) believe we should use this information to improve medical interventions. Chronotherapy is an unusual field with both a long and short history. On the one hand, way back in 1698, English physician Sir John Floyer noticed that he had asthmatic fits after sleeping and, therefore, by late sitting up I have put by the fit for a night or two.
There are also a number of decades-old groundbreaking studies: the Denver asthma report for one, as well as research undertaken in Canada between 1976 and 1991, which found that children given chemotherapy for their leukaemia in the evening had better disease-free survival rates than those treated in the morning. In some areas, timed medicine is already happening, for instance, many doctors prescribe certain statins drugs for high cholesterol to be taken at night to correspond with the time when your body produces the most cholesterol.
But there is still caution. According to Robert Dallmann, a circadian biologist and biomedical sciences professor at the University of Warwick, the field is in many ways still emerging. There was, for a long time, a feeling that this was all much too complicated, he says. While Floyer might have noticed his asthma worsening at night, he wasnt equipped to know why. Notice was only really taken once the field started to get to the molecular mechanisms underlying lots of this, because before it was mostly a black box, Dallmann says.
In 2017, the Nobel prize in Physiology or Medicine was awarded to three American geneticists who had discovered the molecular mechanisms controlling our biological clocks. In laypersons terms: the scientists had isolated a gene that controls the biological rhythms of fruit flies and found that this gene encodes a protein that accumulates within cells at night and degrades during the day. I think the nominators could see all this exciting science and see that it hadnt really translated into the clinic, says Ray. We are in a quite exciting time now where theres a lot of early-phase work showing what massive potential there is here.
Potential, of course, has pitfalls. If scientists discovered that flu vaccinations are more effective in the morning over a decade ago, then why isnt everyone being jabbed at 9am? Well, first, that would mean the NHS could only issue half as many jabs in a week. Second, it can be hard enough getting people to attend their immunisation appointments at all; limiting them to a narrow window could mean that pregnant women with morning sickness miss their appointment, for example, which is far worse than simply being jabbed in the afternoon. Theres also the fact, Ray says, that health systems are bureaucratic, theyre under financial pressure. Its like a supertanker trying to change course.
And, of course, healthcare providers dont want to jump the gun before enough evidence has accumulated. One 2021 study of 63 healthcare workers in China found that Covid-19 vaccines were more effective when given in the morning. Later that year, a study monitoring 2,190 healthcare workers in the UK found that Covid vaccinations had better efficacy in the afternoon. The vaccinations in both studies were different, but a number of other factors complicate analysis of the results; for example, neither factored in participants medication history or sleep and shift-work patterns.
Then theres the matter of funding. For pharmaceutical companies, there are marketing and safety issues when it comes to producing drugs that should be taken at an exact time of day. What are the risks if someone takes it early or late? Already, approximately 30-50% patients with long-term conditions dont adhere to their medication. But even without new medicine, chronopharmacology can be revolutionary: Ray says the field could rescue drugs that have previously failed clinical trials.
Its not uncommon for a drug to be groundbreaking in mice and ineffective in human trials. But in 2020, researchers from Harvard Medical School published a study which found that preventive stroke strategies that had worked in rodents but failed in humans may have done so because rats are nocturnal. Many trials test rats in the daytime, when theyre inactive, and test humans during the day, when theyre active and awake.
They were able to show that a lot of these promising drugs have probably been tested in humans at the wrong time of day, Ray says. Thats millions and millions and millions of pounds wasted and all those volunteers recruited and subjected to a trial. The time of day a drug is administered could also change its side-effects, so drugs that were written off as too toxic could actually be safe within certain parameters. To save money and save lives, Ray argues that many trials should have clock logic embedded into them.
Lets say you need to take a drug at 8am for it to be effective, and for whatever reason needy kids, a hangover, a fundamental disdain for the morning you cant. Theoretically, says University of Oxford pharmacology professor Sridhar Vasudevan, you could take one drug to change the timing of another problem solved. Chronopharmacology isnt just about matching medicines with your circadian rhythms: its also about creating medicine that affects the circadian system itself.
Vasudevan became interested in circadian rhythms when he worked in psychiatry more than a decade ago. He noticed that sleep disturbance was prevalent across the board in depression, bipolar disorder and schizophrenia. When something goes wrong in the brain that leads to a mood dysfunction, you have associated sleep dysfunction, he says. So, Vasudevan theorised, If you can correct the sleep and circadian dysfunction, you can fix the other side, which is the mood.
In 2016, Vasudevan co-founded a company in the Oxford Centre for Innovation, named Circadian Therapeutics. He and his colleagues are identifying drugs to treat diseases related to circadian rhythm disorders. The team are currently working with blind veterans who have disrupted sleep cycles because light cannot reset their circadian rhythms. Basically, theyre constantly jet-legged every single day, Vasudevan says. The idea is to have a drug that can mimic the effects of light on the brain, so that they can take it once a day and stabilise their sense of time.
Circadian Therapeutics are also developing drugs to help those with neurodegenerative disorders. Sundowning is a phenomenon whereby some people with Alzheimers and Parkinsons become distressed and confused in the late afternoon. Vasudevan is looking into circadian modulators that could manage these symptoms.
Of course we shouldnt just manipulate our body clocks for the sake of it, as Vasudevan warns that taking one newly discovered drug to affect the timing of another could introduce extra risk. Still, theres potential. If the ideal time for you to take a drug is between 1am and 4am, most people are not going to wake up to take it, Vasudevan says, and sleep is extremely important in the healing process, regardless of what youre recovering from. In some circumstances at some point in the future taking one drug to change your circadian timing could help another drug work better.
Drugs are not the only route to a healthy life. Chrono-nutrition and chrono-exercise are exactly what they sound like. In October 2021, a study from Harvard Medical School found that eating earlier affects the speed at which you burn calories and store fat in short, the exact same meal could be far healthier eaten at 5pm than 9pm. In May, academics from Skidmore College in New York found that women who exercised in the morning burned more abdominal fat and reduced their blood pressure more than women who exercised in the evening but, the later exercisers had enhanced muscular performance.
Before you start swallowing 10am pills and going on 3pm jogs, its important to remember that our internal circadian biology does vary: some of us are morning people and some of us are evening people (this characteristic is known as a chronotype). Ray says your chronotype is affected by your age, gender and genes, and argues that in the future well likely see personalised chronopharmacology based on the clock phase of the person, rather than just going off the time on the clock on the wall.
Dallmann, who runs the Patho-Physiological Molecular Clocks Lab at Warwick University, has already used his research to work out what personally works for him. I do implement some of the current knowledge on time-restricted eating, he says, and I choose my painkillers differently by time of day.
Still, its important to remember that for many medicines, the time of day theyre taken doesnt matter at all. As Ray says: If the disease you are targeting doesnt change by time of day then it doesnt matter what time of day you give the drug. If a drug has a long half-life (ie it takes weeks for the substance to reduce by half in your body), then the time of day its taken doesnt matter, because its concentration remains consistent.
Sceptical scientists have also warned about being too enthusiastic. University of North Carolina biochemist Aziz Sancar has argued that when it comes to cancer, chrono-chemotherapy researchers have overstated positive findings and generalised from small studies in the past. But for now and for many, chronopharmacology remains emerging and exciting. We have to be careful about overselling it. It can lead to dissatisfaction if you cry wolf, says Ray. However, Were at that point where its exciting, and people are increasingly aware of the field.
Weve done focus groups with patients, Ray says, and as soon as you say: Wed really like to hear your views about timing and how the time of day affects your disease, theyre over the moon because, finally, someone is listening.
Excerpt from:
Time for your medicine: unlocking the power of our body clocks - The Guardian
- BENITEC BIOPHARMA INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) - Marketscreener.com - February 13th, 2023 [February 13th, 2023]
- CENTOGENE to Participate in Upcoming Conferences in February in the Lead Up to Rare Disease Day - Marketscreener.com - February 7th, 2023 [February 7th, 2023]
- Gene | Definition, Structure, Expression, & Facts | Britannica - January 27th, 2023 [January 27th, 2023]
- New gene therapy delivers treatment directly to brain - January 27th, 2023 [January 27th, 2023]
- Indian Pharma Congress: Gene-cell therapy, preventive medicine future of health care, says expert - Economic Times - January 25th, 2023 [January 25th, 2023]
- A blood test that identifies people at higher risk of miscarriage? Thats the goal of this award-winning Rutgers med student. - The Philadelphia... - January 19th, 2023 [January 19th, 2023]
- Gene Therapy: Genes As Medicine | Pfizer - January 6th, 2023 [January 6th, 2023]
- How Genomics will ensure a risk-free and beneficial treatment for good health and well-being - The Financial Express - December 28th, 2022 [December 28th, 2022]
- Regenerative Medicine Advanced Therapy Designation | FDA - December 18th, 2022 [December 18th, 2022]
- 3576 - Gene ResultCXCL8 C-X-C motif chemokine ligand 8 [ (human)] - November 23rd, 2022 [November 23rd, 2022]
- Study identifies new gene that drives colon cancer - EurekAlert - October 17th, 2022 [October 17th, 2022]
- Updated Stroke Gene Panels: Rapid evolution of knowledge on monogenic causes of stroke | European Journal of Human Genetics - Nature.com - October 17th, 2022 [October 17th, 2022]
- The challenges of translating CRISPR to the clinic - Labiotech.eu - October 17th, 2022 [October 17th, 2022]
- Editas Medicine Presents Preclinical Data on EDIT-103 for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa at the European Society of Gene... - October 17th, 2022 [October 17th, 2022]
- 'We have to find a way': FDA seeks solutions to aid bespoke gene therapy - BioPharma Dive - October 17th, 2022 [October 17th, 2022]
- Mathematical model could bring us closer to effective stem cell therapies - Michigan Medicine - October 17th, 2022 [October 17th, 2022]
- Approval, Commercialization Highlighted at Cell & Gene Meeting on the Mesa - Genetic Engineering & Biotechnology News - October 17th, 2022 [October 17th, 2022]
- CANbridge-UMass Chan Medical School Gene Therapy Research in Oral Presentation at the European Society of Gene and Cell Therapy (ESGCT) 29th Annual... - October 17th, 2022 [October 17th, 2022]
- Depression Treatment: How Genetic Testing Can Help Find the Right Medication - Dunya News - October 17th, 2022 [October 17th, 2022]
- The Risk-Reward Proposition for CGT Clinical Trials - Applied Clinical Trials Online - October 17th, 2022 [October 17th, 2022]
- Precision Medicine Could Get Even More Precise With Allarity Therapeutics Next-Generation Diagnostics - Benzinga - October 17th, 2022 [October 17th, 2022]
- Decibel Therapeutics Receives FDA Clearance of IND Application for DB-OTO, a Gene Therapy Product Candidate Designed to Provide Hearing to Individuals... - October 17th, 2022 [October 17th, 2022]
- Replay establishes distinguished Scientific Advisory Board of genomic medicine and cell therapy experts - Yahoo Finance - October 17th, 2022 [October 17th, 2022]
- Scientists Reappraise the Role of Zombie Cells That Anti-aging Medicine Has Sought to Eliminate - Neuroscience News - October 17th, 2022 [October 17th, 2022]
- Forge Biologics Announces Updated Positive Clinical Data in RESKUE, a Novel Phase 1/2 Gene Therapy Trial for Patients with Krabbe Disease - Business... - October 17th, 2022 [October 17th, 2022]
- Gene Expression Signatures Are Analyzed for Biomarkers of Response in HCC - Targeted Oncology - October 17th, 2022 [October 17th, 2022]
- NHS England World-first national genetic testing service to deliver rapid life-saving checks for babies and kids - NHS England - October 17th, 2022 [October 17th, 2022]
- The proteinprotein relationship that could mend a broken heart - RegMedNet - October 17th, 2022 [October 17th, 2022]
- Study finds microprotein correlated to Alzheimers risk - Daily Trojan Online - October 11th, 2022 [October 11th, 2022]
- Passage Bio Announces Appointment of William Chou, M.D. as Chief Executive Officer - Yahoo Finance - October 11th, 2022 [October 11th, 2022]
- Gene Therapy Rapidly Improves Night Vision in Adults with Congenital Blindness - Newswise - October 11th, 2022 [October 11th, 2022]
- Scientists Discover Protein Partners that Could Heal Heart Muscle | Newsroom - UNC Health and UNC School of Medicine - October 11th, 2022 [October 11th, 2022]
- The Pros and Cons of Lentiviral and Adeno-Associated Viral Vectors - The Medicine Maker - October 11th, 2022 [October 11th, 2022]
- Insights & Outcomes: Foreign DNA, quantum potholes and relapsing fever - Yale News - October 11th, 2022 [October 11th, 2022]
- Expediting IND applications with drug master files - BioPharma Dive - October 11th, 2022 [October 11th, 2022]
- UNC School of Medicine Awarded $3 Million to Lead Study to Reduce PTSD Frequency, Severity | Newsroom - UNC Health and UNC School of Medicine - October 11th, 2022 [October 11th, 2022]
- Lineage to Present at Alliance for Regenerative Medicine 2022 Cell & Gene Meeting on the Mesa - businesswire.com - October 8th, 2022 [October 8th, 2022]
- The Next Crispr Gene Editing IPO Could Be Near - Henry Herald - October 8th, 2022 [October 8th, 2022]
- 10-year CRISPR anniversary: How gene editing revolutionized medicine, and what lies ahead - Genetic Literacy Project - October 8th, 2022 [October 8th, 2022]
- Blood from a baby at birth can be gene sequenced to prevent diseases - USA TODAY - October 8th, 2022 [October 8th, 2022]
- What doctors wish patients knew about breast-cancer prevention - American Medical Association - October 8th, 2022 [October 8th, 2022]
- Growth in Cell and Gene Therapy Market - Pharmaceutical Technology Magazine - October 8th, 2022 [October 8th, 2022]
- Gene Editing Service Market 2022 : Top Players to Reflect Impressive Growth Rate till 2029: Caribou Biosciences, CRISPR Therapeutics, Merck KGaA,... - October 8th, 2022 [October 8th, 2022]
- Tip Sheet: $78 million to support new precision oncology institute, update on experimental gene therapy for herpes and the launch of Fred Hutch's new... - October 8th, 2022 [October 8th, 2022]
- Cell and Gene Therapy: Rewriting the Future of Medicine - Technology Networks - October 2nd, 2022 [October 2nd, 2022]
- Growth in Cell and Gene Therapy Market - BioPharm International - October 2nd, 2022 [October 2nd, 2022]
- CRISPR Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX130 for the Treatment of Cutaneous T-Cell... - October 2nd, 2022 [October 2nd, 2022]
- BioMarin Resubmits Biologics License Application (BLA) for Valoctocogene Roxaparvovec AAV Gene Therapy for Severe Hemophilia A to the FDA - PR... - October 2nd, 2022 [October 2nd, 2022]
- Fighting Breast and Ovarian Cancer With a Lupus Antibody - Yale School of Medicine - October 2nd, 2022 [October 2nd, 2022]
- This gene therapy company is testing new tech to 'switch off' diabetes and obesity with a pill - Euronews - October 2nd, 2022 [October 2nd, 2022]
- Tenaya Therapeutics to Participate in Inaugural Hypertrophic Cardiomyopathy Medical Societys 2022 Scientific Sessions - Yahoo Finance - October 2nd, 2022 [October 2nd, 2022]
- Risk of Alzheimer's dementia may be predicted with help of new tool Washington University School of Medicine in St. Louis - Washington University... - October 2nd, 2022 [October 2nd, 2022]
- Tiny Sea Creature's Genes Shed Light on Evolution of Immunity - UPMC - October 2nd, 2022 [October 2nd, 2022]
- Who will get the call from Stockholm? It's time for STAT's 2022 Nobel Prize predictions - STAT - October 2nd, 2022 [October 2nd, 2022]
- Excision BioTherapeutics Awarded California Institute for Regenerative Medicine (CIRM) Grant to Support Ongoing Phase 1/2 Trial Evaluating EBT-101 as... - October 2nd, 2022 [October 2nd, 2022]
- NeuroVoices: Emma Ciafaloni, MD, on the Vast Expansion of Innovative Approaches to Duchenne Muscular Dystrophy - Neurology Live - October 2nd, 2022 [October 2nd, 2022]
- COVID mRNA Jabs and Testing Kicked Off This Industry of Drug Development: Here's What You Need to Know - The Epoch Times - October 2nd, 2022 [October 2nd, 2022]
- Kidney resident macrophages have distinct subpopulations and occupy distinct microenvironments - University of Alabama at Birmingham - October 2nd, 2022 [October 2nd, 2022]
- Nobel Prize for medicine: the full list of winners - The National - October 2nd, 2022 [October 2nd, 2022]
- The surprising link between circadian disruption and cancer may have to do with temperature - EurekAlert - October 2nd, 2022 [October 2nd, 2022]
- The global live cell imaging market is expected to grow at a CAGR of 8.44% during 2022-2027 - Yahoo Finance - October 2nd, 2022 [October 2nd, 2022]
- Chroma Medicine Announces Formation of Scientific Advisory Board of Global Experts in Gene Editing and Cell and Gene Therapy - PR Newswire - September 20th, 2022 [September 20th, 2022]
- Ring Therapeutics Announces Issuance of U.S. Patent for its Anellovector Compositions - Yahoo Finance - September 20th, 2022 [September 20th, 2022]
- Cholesterol gene mutation: Why would a healthy 27-year-old have severe heart problems? - 69News WFMZ-TV - September 20th, 2022 [September 20th, 2022]
- Gene Therapy for Severe Hemophilia B Could Be More Cost Effective Than Current Treatments - Managed Healthcare Executive - September 20th, 2022 [September 20th, 2022]
- AVROBIO Receives Rare Pediatric Disease Designation from U.S. Food and Drug Administration (FDA) for First Gene Therapy in Development for Cystinosis... - September 20th, 2022 [September 20th, 2022]
- The Biggest CGT Breakthroughs Through the Eyes of Our 2022 Power List - The Medicine Maker - September 20th, 2022 [September 20th, 2022]
- Leading Virus Researcher to Chair UVA's Department of Microbiology, Immunology and Cancer Biology - UVA Health Newsroom - September 20th, 2022 [September 20th, 2022]
- Work remains on Tay-Sachs and other Ashkenazi genetic disorders J. - The Jewish News of Northern California - September 20th, 2022 [September 20th, 2022]
- Study Shows Genetic Link to Moving to the Beat of Music - Newswise - September 20th, 2022 [September 20th, 2022]
- Viewpoint: In the post Roe v Wade world, what changes should a biology textbook writer make to address the medical repercussions of Dobbs? - Genetic... - September 20th, 2022 [September 20th, 2022]
- Alnylam Receives Approval in Europe for AMVUTTRA (vutrisiran) for the Treatment of Hereditary Transthyretin-mediated (hATTR) Amyloidosis in Adult... - September 20th, 2022 [September 20th, 2022]
- CSL flexes gene therapy muscle with latest drug - Sydney Morning Herald - September 20th, 2022 [September 20th, 2022]
- The MIT Press releases new book on the science of the heart from cardiac expert Dr. Sian Harding - EurekAlert - September 20th, 2022 [September 20th, 2022]
- Global Pharmaceutical Contract Manufacturing Market is projected to reach a market value of US$329.7 Billion in 2032: Visiongain Reports Ltd - Yahoo... - September 20th, 2022 [September 20th, 2022]
- Alzheon Reports Industry-Leading Biomarker, Brain Preservation and Clinical Effects Following 12 Months of Treatment in Phase 2 Trial of Oral ALZ-801... - September 20th, 2022 [September 20th, 2022]
- Do You Have Lung Cancer With An EGFR Mutation? If So, The Drug Tagrisso Might Be Right For You Based On New Results From A 'Practice Changing' Trial -... - September 20th, 2022 [September 20th, 2022]
- Getting rid of unwanted transformed cells: Possible new directions in cancer therapy - EurekAlert - September 20th, 2022 [September 20th, 2022]
- Sven Kili on reconvening with the ISCT - The Medicine Maker - September 14th, 2022 [September 14th, 2022]
- Study refutes long-held belief that the Corin gene causes hypertension in African Americans - University of Alabama at Birmingham - September 14th, 2022 [September 14th, 2022]