Wednesday April 22 2015
Could the active ingredient in foot cream repair nerve damage?
"Two common drugs – one used for treating athlete's foot and another for alleviating eczema – may be useful therapies for multiple sclerosis," BBC News reports. The drugs have shown promise in lab and animal studies.
Multiple sclerosis (MS) is a neurological condition caused by damage to myelin. Myelin is a protein that acts as a protective layer to individual nerve fibres.
In this study researchers screened a number of drugs used for other conditions in the lab to see if any could produce mature cells to help replace damaged myelin.
One of the chemicals they identified as promising in their screen was miconazole, which is the active ingredient in some types of antifungal creams used to treat athlete’s foot. They found that it increased the number of mature myelin-producing cells in the brains of baby mice. It also helped repair damaged myelin in a mouse model of MS, and this made the mice’s symptoms less severe.
Clobetasol, a steroid cream used to treat psoriasis and eczema, also showed promise.
This is an early-stage study, and researchers hope they can eventually go on to test the drugs, or similar chemicals, in people with MS. Researchers will need to establish how safe this drug is if taken orally, and what effect it has in humans with the condition.
Where did the story come from?
The study was carried out by researchers from the Case Western Reserve University School of Medicine, and other research centres in the US. The study was funded by the US National Institutes of Health, New York Stem Cell Foundation, Myelin Repair Foundation, Mt. Sinai Health Care Foundation, the Case Comprehensive Cancer Center, the CWRU Council to Advance Human Health and philanthropic support from individual families. The authors declared that they did not have competing financial interests.
The study was published as a letter in the peer-reviewed scientific journal Nature.
BBC News gives a good, balanced report of this study, noting the early stage of the findings, and warning of the potential risks of people self-medicating.
The Daily Telegraph reports the study reasonably well, but refers to the drug as a possible "cure", when it is too early to talk about the drug in these terms.
What kind of research was this?
This was laboratory and animal research that aimed to identify known human drugs that can prompt immature oligodendrocytes (called progenitor cells) to mature. Mature oligodendrocytes are the cells that "insulate" nerves with myelin. This myelin sheath helps nerves to send messages, and damage to the myelin sheath causes conditions such as multiple sclerosis (MS). One way to repair this damage might be to prompt the body to make more oligodendrocytes.
This type of screening of large amounts of chemicals at once is a quick way to find promising chemicals. These drugs need to be shown to be effective and safe in animal models before they can be used in humans. If a drug is already licensed for another condition in humans this can make progress to human trials quicker if it is going to be given at a similar dose and in the same way. However, if dose or how the drug is given are likely to differ for the new condition, safety would still need to be established in animals first.
What did the research involve?
The researchers tested more than 700 drugs on mouse oligodendrocyte progenitor cells in the lab. These immature cells are derived from stem cells, and the researchers singled out the drugs that caused them to develop into mature oligodendrocytes. They then tested their effects in brain tissue and in mice, including mouse models of MS, as well as on human oligodendrocyte progenitor cells in the lab.
In human MS, the immune system mistakenly attacks the body’s own myelin. The researchers used two different mouse models of the disease. In one "immune driven" model the mice’s immune system is actively attacking the myelin, and mimics the relapsing remitting form of MS. In the second model the immune system is not as active, and it is has more chronic progressive loss of myelin.
What were the basic results?
The research identified 22 drugs that prompted the oligodendrocyte progenitor cells in the lab to mature. They then picked the two drugs that were the best at getting the precursor cells to mature in brain tissue from young mice in the lab. These drugs were miconazole, which is currently used in antifungal creams, and clobetasol, which is a steroid used in creams (topical corticosteroid) for skin conditions such as psoriasis and eczema. They also found that drugs prompted human oligodendrocyte progenitor cells to mature in the lab. Of the two drugs, miconazole had the greater effect.
They found that giving the drugs to baby mice increased the number of myelin-producing cells in their brains. They also helped repair damaged myelin in the spinal cords of mice treated with a myelin-damaging chemical.
In the "immune driven" mouse model of MS, injections of clobetasol – but not miconazole – dampened down the immune response and reduced the severity of the mice’s symptoms. Steroids are known to affect the immune system, so the researchers had expected this. In the chronic mouse MS model, which has hind-leg paralysis, both clobetasol and miconazole injections helped to re-myelinate damaged nerves in the spinal cord and improved the mice’s movements.
Most existing MS drugs act by affecting the immune system, but miconazole did not appear to do this. Therefore the researchers felt this showed more promise as a new way to treat the disease. To show that their results were correct they had another lab confirm their miconazole results in the chronic MS mouse model.
How did the researchers interpret the results?
The researchers concluded that their screening system allowed them to rapidly identify drugs that have potential for re-myelination. This allowed them to identify two existing human drugs – miconazole and clobetasol – which increase re-myelination of nerves and "significantly reduce disease severity in mouse models of MS". They say that this "raises the exciting possibility that these drugs, or modified derivatives, could advance into clinical trials for the currently untreatable chronic progressive phase of MS".
This laboratory and mouse study has identified two drugs currently used for skin conditions – miconazole and clobetasol – that showed promise for treatment of conditions caused by myelin damage, such as MS.
If a drug is already licensed for another condition in humans, this can make progress to human trials quicker if it is going to be given at a similar dose and in the same way. However, as the researchers point out, these two drugs are licensed for use on the skin – not to be taken orally or injected into the system. This means more work will be needed to ensure the drugs are safe enough to be used in this way in humans. The drugs' chemical structures may need to be modified to make them work efficiently and reduce side effects.
Existing MS treatments act by dampening down the immune system, which attacks the myelin, so drugs that act in a different way, by repairing the myelin damage, could bring additional benefit. As yet, research into these drugs for MS is at an early stage, but many people will await with interest to see whether this early promise translates into better treatments.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.