Wonder drug that can 'cure Alzheimer's and MS'
6:02pm Thursday 26th July 2012
6:02pm Thursday 26th July 2012
The Sun heralds the arrival of a new “wonder pill” that “could cure strokes”. Other newspapers highlight the potential for the drug to “cure Alzheimer’s, Parkinson’s and multiple sclerosis”.
The headlines are misleading for three main reasons:
This small study in mice showed the benefit of an experimental drug (MW-151) for reducing the overproduction of “proinflammatory cytokines” in the brain. These chemicals are reportedly associated with Alzheimer’s disease progression.
The mice in the experiments were genetically modified so they developed changes in the brain similar to those in Alzheimer’s, including increased cytokine levels. The drug was effective only when given three times weekly in the early stages of disease and when treatment was continued over an extended period of time.
Animal studies represent an early stage in the development of drugs for human disease but there are many important hurdles to overcome before an effective treatment for humans may emerge. Even if MW-151 does prove to be both safe and effective in humans, it could be many years before it becomes publicly available.
The study was carried out by researchers from the University of Kentucky and Northwestern University Feinberg School of Medicine, Illinois (USA) and was funded by a number of charitable organisations as well as the US National Institutes of Health.
The study was published in the peer-reviewed science journal The Journal of Neuroscience.
Many headlines are potentially misleading, implying that a “wonder pill” for conditions such as stroke, Alzheimer’s, Parkinson’s and multiple sclerosis is just around the corner.
The headlines are misleading in referring to a pill, since the drug was given by injection. Also, the study only researched the effect on Alzheimer’s-like disease in mice and not other conditions including stroke. However, some articles do make clear in the body of the text that these are “early results from animal studies”.
This was an animal study testing the effect of a new drug on the brain cell function of mice bred to exhibit Alzheimer’s-like disease, with the aim of treating their disease.
In humans, Alzheimer’s disease is characterised by protein ‘plaques’ and ‘tangles’ that build up in the brain leading to the loss of functioning brain cells. The researchers said that the overproduction of chemicals in the brain called proinflammatory cytokines has been linked to Alzheimer’s disease progression and that previous animal studies have shown that blocking these cytokines could help reduce some of the biological processes of the disease.
This study sought to test an experimental drug that inhibits the production of proinflammatory cytokines to see whether it would be therapeutically beneficial to mice that were bred to develop Alzheimer’s-like disease.
A new drug called MW01-2-151SRM (MW-151), that selectively inhibits the production of proinflammatory cytokines, was given to mice exhibiting Alzheimer’s-like disease to see whether it helped the disease.
Mice were bred to develop Alzheimer’s-like disease that got worse with age (mimicking the human disease) and that included increases in levels of proinflammatory cytokines – chemicals thought to be associated with the progression of the disease.
The drug was administered during two distinct but overlapping time periods. One was an extended treatment period starting in the early stages of the mice model of Alzheimer’s, and the second was a short-term treatment when the mice were slightly older. Each treatment group consisted of 12 mice. The first extended treatment period involved giving the mice a low dose of the drug (2.5mg/kg) by injection into their abdomen three times a week from when the mice were six months old to when they were 11 months. The second treatment (short term) involved giving the same dose by injection, but this time it was given every day for one week and when the mice were 11 months. Control treatments were also used, which contained no drug and were just saline solution.
Following the treatment, the mice were killed and their brains removed. Their brains were examined in the laboratory for biological signs of Alzheimer’s disease, including levels of cytokines, amyloid plaque and nerve signalling proteins, and nerve function was tested. The presence of amyloid plaque is one of the main features associated with Alzheimer’s disease.
The brains of the mice given the drug were compared to those that were given the inactive control treatment to observe any differences associated with the drug.
The researchers reported that:
The researchers concluded that the new drug was effective at reducing the overproduction of proinflammatory cytokines by targeting the cells that produce these chemicals. Similarly, that this prevents the loss of important proteins and maintains nerve functioning. They concluded that the beneficial effects of the drug occurred in the absence of changes in the level of amyloid plaque.
They importantly highlight that the drug seems most effective when given early in the disease course, before the full-blown disease has emerged.
This small study in mice shows the benefit of an experimental drug (MW-151) to reduce the overproduction of proinflammatory cytokines in the brain, which are thought to be associated with Alzheimer’s disease progression. The drug was only effective when started when the mice were six months old – early in the disease course – and given over an extended period of time. Shorter treatment with the drug given at a later stage of the disease when the mice were aged 11 months was much less effective.
This interesting study will undoubtedly guide further research into this drug, but the following limitations should be borne in mind:
The study was in mice, not people. Studies in mice are useful to test how new chemicals may treat a disease in an animal, but drugs that show promise in mice do not always work on humans. Only after human trials conclude will we be able to assess whether it is safe and could benefit people. This process of drug development and testing can take a long time and there is no guarantee that a drug showing promise in mice will lead to a treatment in humans. Early animal studies represent only the beginning of the development of drugs for humans – there are many important hurdles to overcome before the process may result in a usable drug.
Exaggeration of findings in the media
This research focused on the effect of this drug on mice exhibiting Alzheimer’s-like disease. A lot of news coverage extrapolated the findings to other conditions and diseases where cytokines are thought to play a role, including stroke, Parkinson’s and multiple sclerosis. None of these conditions were modelled or tested in this research and so the effect of the drug on these diseases, even in mice, is speculative, and not supported by this research.
Difficulty translating findings to a useful therapy
The authors highlight that while some improvements were seen with the later short-term intervention, the earlier and more prolonged intervention yielded much better effects. The authors also implied that early prolonged treatment was initiated before the onset of any symptoms. Translating this to humans means that if this drug has any therapeutic potential at all in humans, it may only be effective in preventing progression if given very early in the disease course – not as a treatment that could reverse Alzheimer’s in people who have established disease.
No result for key outcome measure
Importantly, neither dosing regimen had a detectable effect on amyloid plaque load. The presence of amyloid plaque is one of the main features associated with Alzheimer’s disease and thought to cause many of the symptoms of Alzheimer’s. So, as this drug does not affect this key characteristic it is unclear to what extent it would alleviate the symptoms or functioning of an individual with Alzheimer’s. This is the crucial and most important effect of any Alzheimer’s treatment.
‘‘Wonder pill’ that could cure stroke’. The Sun, July 26 2012
‘Single pill could treat Alzheimer's, Parkinson's and MS’. The Daily Telegraph, July 25 2012
‘A single pill could treat Alzheimer's, Parkinson's AND multiple sclerosis’. Daily Mail, July 25 2012
Bachstetter AD, Norris CM, Sompol P, et al. Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction in a Mouse Model That Exhibits Age-Dependent Progression of Alzheimer's Disease-Related Pathology. The Journal of Neuroscience. Published online July 25 2012
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