mable_health

We believe both vascular and neuronal factors play a role in the development of migraine.

A fantastic genetic study (https://www.nature.com/articles/s41588-021-00990-0) that came out in February (but which was out as a pre-print for a decent while before then) offers good support for this view.

It identified a large number of genetic variants predisposing individuals to migraine, and showed these are enriched in genes specifically expressed in the brain (caudate, basal ganglia) and in cardiovascular tissues (aorta, tibial artery, coronary artery).

Clinically migraine presents often very distinctly with symptoms including headache on one side, nausea, vomiting & sensitivity to light among others, while with cluster headaches people often have a single red, teary eye with "clusters" of headache attacks over time.

- Your Mable Team Members, Dr. Kumeren Govender [Chief Medical Officer] and Chris Eijsbouts [Chief Scientific Officer]

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Hi /u/Nikola___Tesla,

We indeed provide our customers with a report that includes the variants you have in/around genes we use to individualize your treatment plan. Whilst there are genetic markers that can be used to infer predisposition to migraine, our core focus right now is instead on drug response. In the future, we hope to expand our offering to also include estimating migraine risk using these markers.

Providing an indication of your genetic predisposition to migraine relative to the rest of the population is already technically possible using the data we're collecting for customers right now, on the basis of large-scale studies of genetic predisposition to migraine (see e.g. Gormley et al. 2016) and its successor (Hautakangas et al. 2022), and we're working on the regulatory and presentation aspects to make this happen!

-Your Mable Team members, Dr. Tom Kent [Chief Technology Officer] and Chris Eijsbouts [Chief Scientific Officer]

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Hi u/bignateyk,

We really sympathize with all migraine patients when a migraine gets you completely down, and we certainly hope that we can help to improve the frequency and/or severity of your wife's migraine attacks. It's important to have an individualized approach, as we all experience life and illness differently.

Mable uses DNA information to look at likely responses to medication, and our clinical team looks for contributing factors that lead to migraine, or the absence of protective factors. In many people living with migraine, there is a problem with certain nerves supplying the blood vessels inside the brain. Either pain is transmitted along these nerves, or the nerves release pain-causing chemicals, causing the headache symptoms associated with migraine.

Sumatriptan acts like Serotonin, which is a chemical messenger used to send signals between nerves in many different parts of the body. Serotonin has many different effects on the body, however, you are probably most familiar with its role as the “happy hormone.” How serotonin is involved in migraine is complex; research has shown that serotonin acts directly on blood vessels in the brain, upon nerves that control how pain is sensed, and via a broad network of nerves projecting from the base of the brain (the brainstem) into almost all areas of the brain. (You may see Sumatriptan referred to as a Serotonin (5-HT1) agonist.) Sumatriptan has three different modes of action:

- Activation of specific nerves that use Serotonin.- Prevents the release of pain-causing chemicals.

- Adjusts the circulation of blood in the brain.

- The combination of these mechanisms can reduce the level of pain that a patient experiences.

This in turn helps to relieve migraine symptoms once a migraine starts to appear. https://www.trymable.com/medication/sumatriptan

However, there are newer forms of migraine analgesia or acute medication, such as CGRPs which may be alternative options to consider!

(Source: https://www.trymable.com/blog/nurtec-rimegepant-migraine)

- Your Mable Team Member, Tom Lovejoy MBBCH (MD)

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Hi /u/Whybecauseoh,

Thanks for the great question! At the moment we've got our patent-pending, so we are not at full liberty to disclose technical details. Amongst others, for instance, some SNPs that we look at underlie previously established pharmacogenetic recommendations, based on studies using a variety of outcomes (e.g. drug discontinuation or variation of serum concentrations by genotype, [CPIC lists such studies for amitriptyline on p. 26 here.]

There's a growing number of pharmacogenetic studies coming out, and we believe it's very likely that additional genetic associations will be found in the near future. A part of our internal research efforts goes towards discovering more of them so that we can keep making continuously better predictions for our members over time.

- Your Mable Team Member, Dr. Roman Rothaermel [CEO]

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Hi /u/Kainiaa! Thanks for your question. There is a wealth of literature evidence that links your DNA (or mutations in it) to both the onset of migraine and your responses to treatments. At Mable, we're currently focusing on the latter - with the aim to improve the often laborious process of finding the right treatment for you. Because of this, we're not currently investigating diagnostic genetic markers for migraine. Nevertheless, there is a whole field dedicated to genetically predisposed migraine subtypes such as Familial Hemiplegic Migraine, a rare monogenic form of migraine (included in the review here), but also migraine with and without aura, which recent evidence suggests are genetically distinct, but which are both influenced by a wide range of variants across the genome. In the future, we do hope to expand our DNA test to encompass migraine diagnosis, but right now we're focused on treatment.

In regards to the treatment side of things, there is a wealth of evidence out there to support the idea that mutations in your DNA, particularly in regions and genes associated with the metabolism of drugs, has a significant effect on the efficacy of your medication and the side effects you experience (reviewed by e.g. the Clinical Pharmacogenetics Consortium or the Dutch Pharmacogenetics Working Group). This is the case for a number of medications used to treat migraines. If you carry a mutation in such a gene that is involved in the metabolism of your migraine medication, you might find that your medication doesn't work very well to reduce your migraines, or you might find that you experience more side effects than other people. Because of the wide array of possible medications used to treat migraine, it's really a case of trial and error to find a medication that works well for you and has a tolerable level of side effects. This is where we come in, we look at hundreds of genetic markers to estimate whether a drug will have low efficacy or greater side effects and use that information to help you find a medication that should work well for you.

--Your Mable Team Members, Dr. Tom Kent [CTO] and Chris Eijsbouts [CSO]

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