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expert reaction to LMTX drug for mild Alzheimer’s disease

A study published in the Journal of Alzheimer’s Disease investigated the effect of a low dose drug targeting the tau protein as a treatment for mild Alzheimer’s disease.


Prof. John Hardy, Professor of Neuroscience, UCL, said:

“Previous trials reported on this drug in 2016 were negative. There has been little or no animal work suggesting efficacy. This report should not be interpreted as indicative of efficacy without a further trial.”


Prof. Robert Howard, Professor of Old Age Psychiatry UCL, said:

“When looking at this report is important to bear in mind that in both this and an earlier clinical trial in people with Alzheimer’s disease, LMTX failed to show superiority over placebo on the main study outcomes and according to the original analysis plan. By the conventional standards of analyzing and reporting clinical trials, the results are therefore negative and should be treated and reported as such.

“There are good reasons why we analyze and report trials correctly. Changing analyses late in the life of a trial and picking and choosing peculiar secondary subgroup analyses to report increases the risk that what may appear to be a ‘significant’ effect of a treatment will emerge purely by chance. This difficulty has particularly dogged the field of Alzheimer’s disease research and is one of the reasons that so many drugs have been reported to work in early phase trials, only to prove costly failures in larger and well-conducted phase 3 studies.

“I take serious issue with the claims made for these data and the irresponsibility of potentially raising false hope among patients and their families based on them. If there’s a positive signal in the data, the veracity and significance of this now needs to be tested in a further trial within which patients who are not taking one of the other Alzheimer’s treatments are randomly allocated to LMTX or an appropriate placebo. If such a trial yields a positive result, then that will be a real cause for celebration in our field.”


Prof. Clive Ballard, Professor of Age-Related Diseases, University of Exeter Medical School, said:

“The authors have revisited their study and revised the analysis of the outcomes they were reporting on after their initially stated aims were unsuccessful. It shows promise for a further trial but should not be over-interpreted at this stage.”


Prof. Tara Spires-Jones, UK Dementia Research Institute Programme Lead and Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh, said:

“There are several limitations of this study that mean we do not yet know whether this treatment will help people with Alzheimer’s.  There was not a placebo control group, the numbers of people taking the new drug alone were quite small, and those people who were given the new drug on its own (without other standard treatments) were less impaired at the beginning of the study, so the slower progression could be due to them being healthier to begin with.”


Dr David Reynolds, Chief Scientific Officer, Alzheimer’s Research UK, said:

“This trial was designed to test a drug that targets the build-up of abnormal tau protein, a hallmark of Alzheimer’s disease and several other forms of dementia. Despite a lack of clarity around exactly how LMTX targets tau, there has been much hope about the benefits a drug against this process could bring for people living with dementia.

“A previous study tested LMTX in a group of people with mild to moderate Alzheimer’s, most of whom were taking existing, approved Alzheimer’s medications. While overall LMTX did not lead to the benefits researchers were hoping to see, the results pointed to potential improvements in a small number of people who took the drug by itself and not in combination with existing Alzheimer’s drugs.

“The results published this week also showed some potential benefits for LMTX as a monotherapy when compared against its effects alongside existing Alzheimer’s drugs, but we can’t draw any firm conclusions without more research. There are a number of reasons people with Alzheimer’s may not take currently approved medications and, while the researchers tried to take these into account, they may explain why the disease appeared to progress more slowly in people who took LMTX as a monotherapy.

“In order to get a clearer idea of the effects of LMTX, we now need to see carefully planned studies that focus on LMTX alone, and don’t involve people who are taking other Alzheimer’s medications.”


Dr James Pickett, Head of Research, Alzheimer’s Society, said:

“When the results of the LMTX drug were first presented in 2016, questions were raised amongst the research community about how the results were interpreted. This newer trial takes a different analytical approach and while we encourage researchers to explore all potential angles in their data, there are some issues remaining that mean we cannot interpret this data as a positive result. These issues include the lack of a strong control group and that the numbers of people who were taking LMTX alone are quite small.

“We have been waiting more than 15 years for a new drug for dementia. Most of the drugs tested so far have targeted the Alzheimer’s hallmark amyloid protein. This was the first large-scale trial to target another potential culprit, the tau protein. From the results that we have seen, we cannot say that LMTX is an effective drug for Alzheimer’s. However, we look forward to seeing other innovative approaches to drug development in dementia, including targeting treatments at more than just the amyloid protein.”


* ‘Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer’s Disease: Cohort Analysis as Modified  Primary Outcome in a Phase III Clinical Trial’ by Wilcock et al. was published in Journal of Alzheimer’s Disease on Tuesday 28th November. 


Declared interests

Prof. Hardy: “John Hardy consults for Ceracuity.”

Prof. Howard: “I have received grants to conduct dementia trials from the Alzheimer’s Society, MRC and NIHR.”

Prof. Ballard:None”

Prof. Spires-Jones: “I am employed by the University of Edinburgh and am a member of the Grant Review Board for Alzheimer’s Research UK.”

Dr Reynolds: “No interests to declare”

Dr Pickett: “Nothing to declare”

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