Chronotherapy: The science of timing drugs to our Body Clock

drugBeing in tune with your natural Body Clock is about a lot more than knowing whether your are a “lark” or an “owl”.

As the BBC’s Day of the Body Clock has shown, it can also have a profound effect on our health.

Doctors are becoming increasingly interested in the science of chronotherapy – aligning medical treatment to our circadian rhythms.

Cancer and rheumatoid arthritis are two disease areas where chronotherapy is showing promise.
Chemotherapy

Every three weeks Philippe Maillol makes the 500 mile round trip from his home in Limoges to Paris for cancer treatment.

He was diagnosed with pancreatic cancer in August 2013 and began standard chemotherapy in Limoges with the drugs infused during the day.

But the side effects were hard to bear.

“I was completely exhausted,” said Philippe. “When I got home from my local hospital I couldn’t even speak, let alone eat. I suffered extreme nausea which lasted for days.”

Six months ago Philippe switched to treatment at the Paul Brousse hospital in Villejuif in southern Paris.

Now his drug infusions are spaced during the day, with two happening overnight while he sleeps.

“The impact on my body is much gentler” he said. “So much so that I don’t need to take the anti-nausea drugs which themselves carried their own side-effects.”

He treatment is being led by Professor Francis Levi, one of the pioneers of chronotherapy.

He said: “We have clocks within our cells that govern the metabolism of drugs. So some drugs are best given at night and others during the day.

“We have found chronotherapy is reducing the toxicity of treatments and improving the quality of life of patients, by respecting the circadian rhythms of the patients.

Prof Levi is taking up a post at Warwick Medical School later this year.

He plans to continue his research into cancer chronotherapy and will treat patients at University Hospital Birmingham.
Rheumatoid arthritis

The University of Manchester is conducting a small chronotherapy trial for rheumatoid arthritis.

The inflammatory condition causes pain and swelling in the joints.

Ten patients are having their sleep/wake cycle and movements monitored for a week, culminating with a 24-hour stay at Manchester Royal Infirmary.

During this visit, their blood and saliva are analysed to examine immune cells.

Krystal Fayle, 27, is one of those on the trial.

She said: “I wake up in pain every day and it often hurts to walk.

“I don’t really go out much anymore because I can’t stand for long because my joints are swollen.”

Patients with rheumatoid arthritis commonly find their symptoms are worse in the morning. But now doctors realise this is not simply because joints stiffen up through lack of use overnight.

“Rheumatoid arthritis is driven by cells in the immune system called T lymphocytes” said David Ray, Prof of Medicine at University of Manchester.

“These cells each have their own clock, and their inflammatory response varies depending on the time of day.

“Even when we remove them from the body and look at them in a dish they still keep a day/night rhythm.”

Some of the drug treatments for rheumatoid arthritis are relatively toxic and carry a significant risk of side effects.

The trial is trying to determine the best time to deliver drugs so that they dampen the immune system only when needed.

Prof Ray said: “The processes that drive the disease are only active for part of 24 cycle – so if get our potent drug in at the right time we can avoid exposing patients to toxic drugs throughout the day.”

Krystal Fayle suffered liver damage from one drug and hair loss from another. So she is hoping that the trial may identify a better treatment.

She said: “To have a drug that worked for me would be absolutely brilliant, and make life much easier.”

The trial is still recruiting but should be completed later this year.

Timing medical treatment to fit our natural biological rhythms is still unusual.

Further patient trials of chronotherapy are needed for what remains an area at the fringe of medicine.

But it is a concept that is gaining ground as more doctors realise the importance of our body clock.

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