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Updated: 1 day 6 hours ago

Will a 'wonder drug' be available in 10 years?

Mon, 2014-09-29 04:50

"Wonder drug to fight cancer and Alzheimer's disease within 10 years," is the headline in The Daily Telegraph.

This headline is a textbook example of hope (and hype) triumphing over reality, as the new "wonder drug" is neither available today nor inevitable in the future.

The headline was based on a study that provides new information about the role of the protein N-myristoylation (NMT) in human cells and a mechanism that inhibits it.

The study's authors suggest NMT could be involved in the development and progression of a range of diseases, including cancerdiabetes and Alzheimer's disease.

Inhibiting the actions of NMT could help combat these diseases. But this remains to be seen: if true, this greater understanding may open up new avenues for medical research, which could ultimately lead to new treatments in the future.

While the results are both intriguing and promising, it is very difficult to predict the precise route or timing of future medical developments (drugs, treatments or therapies) based on early laboratory investigations.

Even if treatments based on NMT inhibition were developed and found to be effective, there is no guarantee they would also be safe or free from serious side effects.

All in all, the 10-year timeframe suggested by The Daily Telegraph should be taken with a pinch of salt.

 

Where did the story come from?

The study was carried out by researchers from Imperial College London and was funded by Cancer Research UK, the Biotechnology and Biological Sciences Research Council, the Engineering and Physical Sciences Research Council, the European Union, and the Medical Research Council.

It was published in the peer-reviewed journal Nature Communications.

While The Daily Telegraph's hyped-up headline was a little over the top, the coverage was accurate and balanced.

Optimistic quotes from the study authors, such as, "Eventually we hope this would simply be a pill you could take. It will be perhaps 10 years or so to a drug 'on the market' but there are many hurdles to get over", were counterbalanced with a note of realism from Cancer Research UK's senior science officer: "The next steps will be to develop this idea and make a drug – but there's a way to go before we'll know if it's safe and effective in people".

 

What kind of research was this?

This was a laboratory-based study looking at the structure and function of proteins in human cells.

Proteins are very important in human biology as they are involved in, or carry out, a huge range of biological tasks and processes.

This study looked at a specific chemical modification called N-myristoylation (NMT), which happens to some proteins as they are being made and after they have been made. This is a very common chemical modification of proteins, which in turn affects their function – a form of regulation.

The researchers say NMT has been implicated in the development and progression of a range of human diseases, including cancer, epilepsy, Alzheimer's disease, Noonan syndrome (a genetic condition that can disrupt the normal development of the body), and viral and bacterial infections.

 

What did the research involve?

The study used laboratory-grown human cells to study all the characteristics of the NMT process. This was achieved by identifying all the proteins undergoing the NMT process and finding out what these chemically tagged proteins did inside the cells, what processes they were involved in, other chemicals they interacted with, and whether the protein NMT process could be stopped (inhibited).

The group studied cells in the laboratory during normal cell function and apoptosis – the natural process in which a cell self-destructs in an ordered way, also known as programmed cell death. Apoptosis is often inhibited in cancer cells, causing them to grow indefinitely and not die.

 

What were the basic results?

The researchers' findings include:

  • Identifying more than 100 NMT proteins present in the human cells studied.
  • Identifying more than 95 proteins for the first time.
  • Quantifying the effect of inhibiting the NMT process across more than 70 chemicals (substrates) simultaneously. This showed which chemicals the NMT proteins were interacting with inside the cells.
  • Finding a way to inhibit the NMT process by inhibiting the main enzyme responsible for the chemical modification, called N-myristoyltransferase.

 

How did the researchers interpret the results?

The research team said: "Numerous important pathways involve proteins that are shown here for the first time to be co- or post-translationally N-myristoylated [N-myristoylated during or after their formation]."

Commenting on the wider implications of their research, they said: "These data indicate many potential novel roles for myristoylation that merit future investigation in both basal cell function and apoptosis, with significant implications for basic biology, and for drug development targeting NMT [N-myristoyltransferase]."

 

Conclusion

This laboratory protein study has provided new information about the role of protein N-myristoylation in human cells and a mechanism to inhibit it. The findings suggest proteins undergoing N-myristoylation are involved in many key biological processes and tasks.

Given the researchers' assumption that protein N-myristoylation has been implicated in the development and progression of a range of diseases is true, this greater understanding may open up new avenues for medical research, which could ultimately lead to new treatments in the future.

However, it is very difficult to predict the precise route or timing of future medical developments (drugs, treatments or therapies) based on early findings.

The study's authors struck a balance of optimism and realism when quoted in The Daily Telegraph.

They first said their findings could lead to new treatments in the future and that, "Eventually we hope this would simply be a pill you could take. It will be perhaps 10 years or so to a drug on the market". Balancing this out, they also said: "There are many hurdles to get over".

This study represents one of the first steps on the road to new drug discovery, so the exact path ahead is unclear.

But despite these promising early findings, there are no sure bets in drug development – the history of medicine is full of initially encouraging avenues of research that ended up leading to dead ends. 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Wonder drug to fight cancer and Alzheimer's disease within 10 years. The Daily Telegraph, September 27 2014

Links To Science

Thinon E, Serwa RA, Broncel M, et al. Global profiling of co- and post-translationally N-myristoylated proteomes in human cells. Nature Communications. Published online September 26 2014

Categories: News

Cherry juice touted as treatment for gout

Mon, 2014-09-29 03:40

“Daily drinks of cherry juice concentrate could help thousands of patients beat gout,” the Mail on Sunday reports.

This headline is based on a small study that found drinking tart cherry juice twice a day temporarily lowered the blood uric acid levels of 12 young healthy volunteers for up to eight hours after they consumed the drink. This is of potential interest, as high levels of uric acid can lead to crystals forming inside joints, which triggers the onset of the painful condition gout.

Somewhat puzzlingly, the study recruited healthy young volunteers who didn’t have gout. A more relevant study design would have included people with a history of gout, to see what effect, if any, cherry juice had on them.

So, based on this study alone, we cannot say that drinking cherry juice helps prevent the onset of gout, or the recurrence of gout in those who have had it before. It is not clear whether reductions in uric acid of the magnitude found in this study would be sufficient to prevent gout or relieve gout symptoms.

The Mail on Sunday’s assertion that “now doctors say drinking cherry juice daily could help beat the condition” is not backed up by this research alone, nor is health advice on gout from health professionals likely to change based on this small study.

 

Where did the story come from?

The study was carried out by researchers from the UK and South Africa, and was part funded by Northumbria University and the Cherry Marketing Institute. The latter is a non-profit organisation, funded by cherry growers, with a brief to promote the alleged health benefits of tart cherries.

This obviously represents a potential conflict of interest, although the research paper says, “The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

The study was published in the peer-reviewed Journal of Functional Foods.

The Mail on Sunday’s coverage over-extrapolates the findings of this small study involving healthy people, not gout sufferers. While it is plausible that cherry juice may be of some benefit to people affected by gout, this is currently unproven.

 

What kind of research was this?

This was a single blind randomised crossover study testing the effects of two doses of cherry juice on levels of uric acid (urate) in the body.

The researchers say that nutritional research has focused more on the use of foods for improving human health, and particular attention has been placed upon foods containing high concentrations of anthocyanins – such as tart cherries.

Gout is a type of arthritis, where crystals of sodium urate form inside and around joints. The most common symptom is sudden and severe pain in a joint, along with swelling and redness. The joint of the big toe is commonly affected, but it can develop in any joint. Symptoms develop rapidly and are at their worst in just six to 24 hours. Symptoms usually last for three to 10 days (this is sometimes known as a gout attack). After this time, the joint will start to feel and look normal again, and the pain of the attack should disappear completely. Almost everyone with gout will have further attacks in the future.

People with gout usually have higher than normal urate levels in their blood, but the reasons for this may vary; for example, some people may produce too much urate, while in others the kidneys may not be so effective at filtering out urate from the bloodstream. The condition may run in families.

This study did not study people with gout, but only looked at the concentration of sodium urate (uric acid) in the blood of healthy young people who did not have gout or high levels of sodium urate, suggesting that they would develop gout in the near future. Hence, it does not provide good evidence that the cherry juice was beneficial to relieve gout symptoms or prevent the recurrence of symptoms.

randomised control trial including people with gout, or people more likely to develop gout (such as older men with a family history), would be required to give us better evidence on the issue.

 

What did the research involve?

The research took 12 healthy volunteers (average age of 26 years, 11 of which were male) and gave them two different volumes (30ml and 60ml) of concentrated cherry juice mixed with water, to see what effect this had on measures of uric acid activity and inflammation up to 48 hours later – both of which are biological measures indirectly related to gout.

None of the volunteers actually had a history of gout.

In an effort to reduce other dietary sources of anthocyanins (outside of that gained from the cherry juice), participants were requested to follow a low-polyphenolic diet by avoiding fruits, vegetables, tea, coffee, alcohol, chocolate, cereals, wholemeal bread, grains and spices for 48 hours prior to, and throughout each arm of the trial. Food diaries were completed for 48 hours before, and throughout, the testing phase to assess the diet for compliance.

Participants were required to attend the start of each phase of the study at 9am, following a 10-hour overnight fast to account for diurnal variation. Each phase was comprised of two days supplementation with cherry concentrate. One supplement was taken immediately following a morning blood and urine sample, and a second consumed prior to each evening meal.

Multiple supplements were administered to identify any cumulative effects. The length of the supplementation phase (48 hours) was chosen due to the short period of time in which anthocyanins are metabolised.

 

What were the basic results?

The main results were as follows

  • Blood urate (uric acid) concentrations in the volunteers went down for both the low and high doses of cherry juice in about the same amount, from around 500 micoMol per litre at the start to around 300 micoMol per litre after eight hours. The concentrations at the 24-hour and 48-hour time points appeared to have increased back up to the 400 micoMol per litre.
  • The amounts of urate (uric acid) removed from the body via urine increased, peaking at two to three hours. The amount excreted then dipped but remained broadly above the starting level up to 48 hours.
  • Levels of a general blood inflammatory marker (high sensitivity C-reactive protein; hsCRP) decreased. 
  • There was no clear dose effect between the cherry concentrate and the biological findings.

 

How did the researchers interpret the results?

The researchers said, “These data show that MC [Montmornecy tart cherry concentrate] impacts upon the activity of uric acid and lowers hsCRP, previously proposed to be useful in managing conditions such as gouty arthritis; the findings suggest that changes in the observed variables are independent of the dose provided.”

They also said, “these results provide rationale for the use of Montmorency cherry concentrate as an adjuvant therapy to NSAIDs [non-steroidal anti-inflammatory drugs] in the treatment of gouty arthritis [gout].”

 

Conclusion

This small study found that drinking tart cherry juice twice a day temporarily lowered the blood uric acid levels of 12 young healthy volunteers without gout, up to eight hours after they consumed the drink. The levels began to increase back to the starting levels after 24-48 hours. The researchers and media extrapolated this finding to mean that the drink may be useful for gout, which is caused by an excess accumulation of uric acid crystals.

Based on this study alone, we cannot say that drinking cherry juice helps prevent the onset of gout, or the recurrence of gout in those who have had it before. The study did not test the effect of the juice on people with gout, or those likely to get gout in the future, so is only indirectly relevant to these groups. For example, it is not clear whether reductions in uric acid of the magnitude found in this study would be sufficient to prevent or treat gout in people with a propensity for high uric acid levels in the body (for whatever reason).

Furthermore, there may have been other dietary factors contributing or interacting with the cherry juice compounds that could account for the changes observed. Hence, cherry juice might not be the sole cause of the effects seen.

The Mail on Sunday carried a useful quote from a UK Gout Society spokesman, who said that while “Montmorency cherries [those used in the study] could help reduce uric acid levels in the body, ‘People with gout should go to their GP because it can be linked to other conditions such as stroke and psoriasis’”.

We find no evidence to support the Mail’s comments that “Now doctors say drinking cherry juice daily could help beat [the] condition”.

For the reasons above, this study alone provides weak evidence that concentrated cherry juice might help those with gout. The media have somewhat overhyped the significance of the findings, which are underdeveloped and tentative. The hype would be justified if a more robust study of people with gout had been undertaken. 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Fighting the agony of gout - with a daily glass of cherry juice. Mail on Sunday, September 28 2014

Links To Science

Bell PG, Gaze DC. Davison GW, et al. Montmorency tart cherry (Prunus cerasus L.) concentrate lowers uric acid, independent of plasma cyanidin-3-O-glucosiderutinoside. Journal of Functional Food. Published online September 27 2014

Categories: News