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Anti-LINGO-1, biotin and phenytoin results reported at AAN 2015

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The 67th annual meeting of the American Academy of Neurology took place in Washington, April 18-25. Pre-meeting media announcements created high expectations for several presentations at the meeting, particularly treatments which may promote remyelination and neuroprotection and potentially slow the build-up of disability.

The AAN meeting is a showcase for the latest developments in the neurosciences.  More than 500 presentations concerned multiple sclerosis alone, covering all areas of MS research.  Don’t forget that at this stage, the findings presented at the meeting have not yet been scrutinised by other scientists working in the same field.  When research is written up for publication in a scientific journal, the peer-review process allows other experts to examine data, criticise and maybe challenge conclusions made by the authors.

Progressive MS treatments

One of the most encouraging aspects of this year’s meeting was the sense that real progress is being made towards therapies which might provide neuroprotection and/or remyelination for progressive MS.

  • Anti-LINGO-1 (also known as BIIB1003)

Researchers reported the results of the RENEW clinical trial which was designed to detect whether treatment with anti-LINGO-1 would result in remyelination.  In this phase II clinical trial BIIB033 was compared to placebo in 82 people who’d recently had a first episode of optic neuritis (but did not have MS).  Participants received a total of six intravenous infusions of the drug or placebo every four weeks and were followed up for a total of 32 weeks.  BIIB033 was no better than placebo at improving vision, but researchers found that the time for a signal to travel from the retina of the eye to the brain (measured by visual evoked potentials) was improved slightly but statistically significantly in those who took BIIB033 – possible evidence that the myelin sheath around the optic nerve had indeed been repaired. 

One observer at the meeting commented that the dose of anti-LINGO-1 was very high and might lead to significant side effects when taken long term, so this will need to be monitored in further clinical trials.

  • High dose biotin (also known as MD1003)

MD1003 is a highly concentrated formulation of biotin, one of the B-group vitamins (vitamin B7).  A phase III study recruited 144 people with secondary or primary progressive MS who were having increasing difficulty with walking and leg weakness. Participants took MD1003 or placebo for up to two years; approximately half of the participants in each group were also taking fampridine.  The main measure of the study was improvement in disability after 9 months of treatment which was still evident at 12 months.  Slightly less than 13% of the MD1003 group and none of the placebo group met this criteria. Further analyses showed evidence of a small decrease in the risk of MS progression; in the MD1003 group there was an average EDSS decrease of 0.03 at month 12, compared with an average increase of 0.13 in the placebo group.

There were no significant side effects although five participants taking MD1003 had “apparent hyperthyroidism”; this could have been caused by high levels of biotin in samples interfering with thyroid hormone blood tests.

One question raised by other researchers is whether the improvements seen are the result of permanent improvement in MS due to remyelinaton or are temporary improvements in MS symptoms.  This could be tested by interrupting treatment – if the improvements remain then this would support remyelination, if improvements were lost, this would suggest that MD1003 is acting as a symptomatic treatment.

The doses being taken in the trial correspond to 10,000 times the recommended daily intake of biotin.   While biotin is available in supplement form, neurologists are warning that people should not start taking large quantities of biotin supplements which are manufactured to a lower quality than the pharmaceutical grade biotin used for this study.

  • Phenytoin

phase II study at University College London involved 86 people with optic neuritis (but did not have multiple sclerosis).  Participants took either phenytoin or placebo for three months. Researchers measured the width of the retina – the layer of nerves at the back of the eyeball – at the start of the trial and after six months. Thinning of the retina is known to indicate damage to nerves elsewhere in the brain and spinal cord.

Results showed that the people taking phenytoin had about a third less damage to cells in the retina than was seen in the placebo group. There was no difference in measures of the quality of vision.

The researchers propose that these results suggest that phenytoin has a neuroprotective effect, protecting nerves from damage and potentially slowing the build-up of disability. Larger studies will be needed to confirm the results of this study.

All of the abstracts from the meeting can be browsed on the AAN website.

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