A conversation with The Professor of Meniere’s Disease

Fascinating insights into the latest research on diagnosis and potential treatments

Like most people with a chronic health condition, I am desperate to understand as much as possible about my condition. Over the years, I’ve read a lot of research studies about Meniere’s and one name has come up over and over again - Professor Jose Antonio Lopez-Escamez. So it was wonderful a couple of months ago to find myself sitting in the sun in Hamburg, Germany with the professor, talking over his long career studying Meniere’s. He very kindly gave up an hour and a half to let me interview him and probe him about his discoveries, so that I could share them with the Meniere’s community. This is an overview of our conversation, and I intend to take a deeper dive into the various topics that come up in later posts - there is a lot to cover!

Jose Antonio Lopez-Escamez is currently Professor of Meniere’s and Neurosciences at the Kolling Institute, University of Sydney in Australia. As an ENT doctor originally in Spain he was working as a consultant in neurotology (the study of complex disorders of the ear, hearing, balance) and published papers on the vertigo-inducing condition known as BPPV (Benign Paroxysmal Positional Vertigo). However the patients he encountered with the biggest problems were very often those with Meniere’s disease. This led to his first research publications in the early 2000s, and he has now been focussing on Meniere’s for over 20 years.

“My view is that patients with Meniere’s disease need a neurotologist, not a general ENT or neurologist “

Overview of the current research

For a long time, Meniere’s has been considered a diagnosis with no known cause. There is a very solid set of international clinical criteria for diagnosis, based on tinnitus, hearing-loss, sense of fullness in the ear and episodic vertigo, and in fact the professor played a significant part in drafting those criteria. However the only common element that anyone could ever point to as a possible “cause” has been a build up in the fluid in one compartment of the inner ear (”endolymphatic hydrops”). Since this excess fluid has always eventually been found in Meniere’s patients, it was thought to be the cause. So treatments have tended to focus on either managing the symptoms or reducing the fluid via diuretics and dietary salt reduction,which is often not effective. Professor Lopez-Escamez has concluded that in fact Meniere’s is not a single condition - the symptoms may all be similar but the causes are varied, and identifiable. His painstaking work has uncovered that up to 40% of patients may have a genetic origin for their Meniere’s whilst the other 60% have some kind of immune system problem. Amongst the immune subgroup, there are 3 additional distinct categories, all identifiable via blood tests - auto-immune, allergic inflammation or auto-inflammation.

The Genetic Subgroup (30-40% of patients)

You don’t need a family history to have a genetic form of Meniere’s. Professor Lopez-Escamez explained that the most important genes involved are “recessive,” meaning you can have a genetic mutation, and suffer from the disease, even if your parents are “completely free of symptoms”. Your inner ear contains tiny hair cells that convert sound vibrations and head movements into nerve signals to the brain. (See this great article to understand these structures in more detail) These genes are responsible for building the tiny, delicate protein links between the hair cells and a membrane above them. A mutation in these genes makes these links “fragile”. A trigger, like an infection, noise trauma, or even a pressure change from a flight, can cause this fragile system to break, kick-starting the disease.

The Immune-Driven Subgroups (about 60% of patients)

For a majority of patients, Meniere’s appears to be a problem with the immune system that can be measured in the blood. This group is split into different types:

The Autoimmune Group (10-20%): In these patients, Meniere’s is associated with an abnormal level of antibodies produced by the immune system falsely thinking that something normal in the body is a foreign invader, and triggering the body’s defences to attack it. These patients will typically have other auto-immune conditions, such as rheumatoid arthritis, lupus, or autoimmune thyroid disease. This is often easy to diagnose with existing blood tests.

The Type 2 Inflammation (Allergic) Group (~25%): This is the most common immune type Professor Lopez-Escamez came across in his study in Spain across multiple hospitals. These patients have high levels of “allergic-type” inflammation markers in their blood (such as interleukin 4, 5 and 13 as well as increased ganulocytes). Importantly, his research found that you don’t need to have obvious “allergies” to be in this group. Your body is simply stuck in a persistent state of allergic-type inflammation that may have resulted from damage to the inner ear.

The Autoinflammatory Group (~13%): These patients show high levels of a specific inflammatory signal called Interleukin-1 beta in their blood. This is a different inflammation pathway that acts like a “warning signal” that won’t shut off, continually requesting the defences of the immune system when they are not required. This signal is broadcast throughout the body, potentially maybe also then triggering Meniere’s to start in the other ear.

Treatment possibilities

Once you realise that Meniere’s has these various different causes, it becomes clear that there won’t be a single “cure-all” treatment that will help all patients. The first step must be to determine which of these subgroups the patient is in, using genetic and blood tests. Professor Lopez-Escamez’s group have done work to show that people don’t switch from one type to another - this is important as it then becomes worthwhile to try to treat the patient knowing they won’t suddenly move from having an allergic-type to an autoimmune response (for example). For the autoimmune group, there are already approaches that a rheumatologist can use to control the body’s over-sensitive immune system. For controlling auto-inflammation a pilot trial is already underway in the US to treat this group using a drug called “Anakinra “ which has shown promise for other autoinflammatory conditions, and it is possible additional autoimmune drugs may be able to be repurposed to treat Meniere’s.

As for the allergic type, another drug Dupilumab that is used for asthma amongst other things will be the subject of a trial on Meniere’s patients in Spain. In addition, it is possible that for this group only, the anti-histamine properties of Betahistine may have some impact. It is important though to understand that all of this is currently experimental - the tests and potential treatments require proper clinical trails before they will become readily available to patients. For those in the genetic group, the idea would be that by testing and discovering early that one has the genetic mutations, the patient could then be more careful to avoid the kinds of trauma that could then damage the hair cells. Longer term, there may be gene therapies to repair the genes, but more funded research on gene therapies for Meniere’s is needed.

What does this mean for “traditional” understandings of Meniere’s?

In the model proposed by Professor Lopez-Escamez, the excess fluid that is the usual focus of descriptions of Meniere’s is just a side-effect of the disease process. It does not cause the condition and may not even give rise to the symptoms. The first event is the damage to the inner ear hair cells, through genetic fragility or inflammation, and only later does this damage mess up the ability of those cells to manage fluid and potassium in the inner ear leading to excess endolymph. This model suggests that the vertigo that plagues sufferers is not some rupture or release of fluid, but rather a storm of electrical activity caused by these hair cells not being anchored and allowing a sudden flood of potassium in the hair cells disrupting the auditory and vestibular nerves.This would also explain why diuretics and often seem to have little or no effect for some patients.

Menière’s Disease Atlas of Genes and Cells

The professor’s group have also launched a globally accessible database to catalog the genes and other biomarkers that correlate with Meniere’s - initially started with data from 425 patients. It is free for scientists worldwide to use as a reference dataset for diagnosis and personalised medicine, and hopefully in the future more datasets will be added to it to build a solid reference base for Meniere’s diagnostics and treatment worldwide.

Questions from the community

Prior to my interview I asked my Meniere’s support group on Facebook (https://www.facebook.com/groups/429718213892938) if they had any questions they wanted answers to. In each case I summarise the response from Professor Lopez-Escamez:

“Are the balance problems I have with Meniere’s ever likely to get better?” - it is important to know if you have Meniere’s in one or both ears. If only one, then the good ear can really help compensate. Try then to get regular vestibular testing as it can help identify early signs of issues with the second ear. Some medication can also interfere with the balance system - in particular some that are prescribed to help with vertigo, if taken long term and very regularly. Consult your doctor of course before changing any medication.

“As a community how can we help support the work you are doing?” - The essential requirement is funding. The North Foundation and the University of Sydney can receive donations, and if you are in Australia charitable donations are 100% tax-deductible. The current work will not be able to continue beyond 2028 without significant additional funding. Even if you can not help directly with funding, please spread the word far and wide about how much good quality research is being conducted here and how much progress is being made.

“Do you have a view on Ebselen (SPI-1005) - the drug being tested for Meniere’s?” - It doesn’t look like it will necessarily be of great benefit for Meniere’s disease. Since it works by increasing the survival of neurons in the inner ear, it will be of more benefit to those suffering ongoing sensorineural hearing loss. This is a perfect example of a drug that tries to be a “cure-all” for Meniere’s - but without knowing which subgroup the patient is in, we don’t know which if any types of Meniere’s it might help with.

Overall, I came away from our discussion with a huge respect for the work of Professor Lopez-Escamez and his group, and also for his incredible openness and willingness to share his time and thoughts with the community. A huge thank you to him for making space in a busy conference to meet me, and for his subsequent time to review and suggest improvements to this article. It would be a terrible shame if such ground-breaking work on Meniere’s had to come to an end, so it is my hope that between us we can find ways to help fund this work, and keep shining the light of good science into the murky darkness of our inner ears.

How to contribute to Meniere disease research:

• Contact: University of Sydney, fmh.philanthropy@sydney.edu.au

• North Foundation Meniere’s research fund info@northfoundation.org.au

• https://northfoundation.org.au/stories/breakthrough-in-menieres-disease-research/