We're Mable, the first company to individualize migraine care by using DNA.

we believe that a scientific and individualized approach to treating migraine creates an incredible opportunity for relief that works.

Where is a double blinded controlled test of this vs a non individualized approach?

Is this approved by the FDA?

What is the efficacy compared to normal treatment?

• crickets *

Most of our doctors and scientists were sleeping, though I went to wake them up based on demand for an answer.

Good questions! While our product focussing on migraine is new, pharmacogenetics-guided therapy has previously shown improved response and remission rates in blinded randomized controlled studies (e.g., for MDD in Greden et al. 2019, involving drugs also commonly prescribed for migraine.)

This test is an approved Laboratory Developed Test regulated under the Clinical Laboratory Improvement Amendments programme regulated by federal regulatory standards.

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

EDIT: Added another link in the second sentence and fixed first link.

1. That is a bad link. It points to nothing. I assume the link should be https://pubmed.ncbi.nlm.nih.gov/30677646/ It address Major depressive disorder, not migraines.
   It's top line finding is "At week 8, symptom improvement for guided-care was not significantly different than TAU"

2. You are selling and advertising a product with no published clinical trial addressing migraines.

3. You have no efficacy data compared to a baseline.

Why on earth is a Reddit AMA an outlet for this? Why are you not in clinical trials instead of selling untested treatments directly to patients?

Hi u/haplo_and_dogs,

​

1. Link is fixed, thanks for pointing this out. We believe a significant increase in response, which the study shows can really help patients (the sentence you quote ends in "improvements in response (26.0% versus 19.9%, p = 0.013) and remission (15.3% versus 10.1%, p = 0.007) were statistically significant"). A closer look at Fig. 1 also reveals a very promising trend for symptom improvement (which may require N>1167 to detect at p<0.05). While there are few studies that directly address treatment efficacy in migraine relative to studies in other disorders, there's substantial overlap between the treatments commonly prescribed for migraines and MDD, hence the relevance of this study. Triptans are a notable example, with the use of genetic data to predict triptan response is well illustrated in this migraine-oriented study.

2. Conducting a clinical trial is certainly on our radar, but takes time, and we believe sufficient evidence exists to make a difference for migraine patients now. We respect that some individuals may wish to wait longer than others to jump on board. We are also working to increase access to treatment as usual, sans genetic tests, at reduced cost.

3. We collect efficacy data at baseline, and have also previously collected data on 700 migraine patients showing that patients taking treatments our algorithm recommend experience greater treatment efficacy and treatment satisfaction. This is research we hope to expand on and publish!

- Your Mable Team Member, Chris Eijsbouts [Chief Scientific Officer]

How is DNA related to migraine treatment?

Hi u/ZanonDF,

Important question! It's common for people with migraine to find they don't respond well to drugs that worked great for others. Just to illustrate the severity of this problem, about 75% of patients starting on oral preventative treatments have given up on them after 6 months (many earlier on, Fig. 3 in this paper) has a good illustration). Similarly, for people with migraine using acute treatments, the majority of people surveyed would seek to try an alternative. In short, rather than everyone sticking to a treatment that's universally the best, there's a lot of switching between drugs in an attempt to find the right fit.

We collect DNA to aid in drug selection. Practically, we provide access to clinicians who are made aware of treatments that we expect won't work well given your genetic background, because they cause side effects or lack efficacy in people with a genetic background like yours. The underlying biological reason is that DNA encodes for the enzymes metabolizing these treatments, such that variation in your DNA leads to abnormal drug metabolism. Amitryptyline, a preventative migraine treatment, for example, is metabolized by CYP2C19 and CYP2D6, and so we look for variation in these genes that tell us you might metabolize this treatment differently from others (which is surprisingly common -- here's a good Stanford study that came out last year). This can lead to recommendations such as "avoid use" or "change starting dose", which are generally agreed upon by large research initiatives such as the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium.

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

EDIT: Added space to make it easier to read

If there's an additional benefit to personalizing migraine treatment, then I'm curious what pre-clinical or clinical research has been performed that supports the ability of gene markers to prognose and elucidate the importance of various risk factors or interventions when treating migraines.

.

Wouldn't your team's ability to better treat migraines also depend on the type of migraine and markers you employ? (e.g. do basilar migraine with vertiginous components share the same informative risk alleles as migraines with classical profiles?)

As a result, I'm curious if there are specific types of migraines you're initially focusing on and if an early consultation helps your team identify whether a patient is suitable for your approach.

Hi u/MattyEC,

Good question! Pharmacogenetics is a really active field at the moment (in part because it's gotten a lot cheaper to read people's DNA for research or clinical purposes), so there are many independent studies coming out. These are generally reviewed by larger research collaborations such as the Dutch Pharmacogenetics Working Group or the Clinical Pharmacogenetics Implementation Consortium. Here's an example of what such a [review] looks like for the way in which genetics determine response to amitriptilyne (listing studies on various outcomes, from serum concentrations to discontinuation), one of the more common TCAs prescribed to prevent migraine days. The FDA has also recently started collecting and listing (in a more limited way) evidence for pharmacogenetic associations, including evidence from industry "stakeholders" that wouldn't normally be published. While the initiatives mentioned above all mention specific markers around known pharmacogenes (e.g. CYP2D6), the field will likely shift to using many more loci across genome to improve drug response predictions going forward (e.g. in this [work coming out of Denmark]), using a genetic risk score on the basis of many genetic loci to predict triptan response).

Your second question, about the importance of migraine subtypes in personalized treatment, touches upon one of our research interests. There is mounting evidence showing that migraine with and without aura have distinct genetic architectures (e.g. in the [largest genetic study of migraine risk to date]). This doesn't necessarily mean that the loci informative of drug response are distinct between these conditions, however. Your risk of having an adverse event, for example, could be explained by loci involved solely in drug metabolism, distinct from the loci influencing your risk of having either subtype (which impact e.g. neurovascular pathways, and not drug metabolism). We are actively collecting data for subtyping to get at this question, but currently, we focus on treating migraine with and without aura -- we do screen to see if people have any "red flags" that warrant immediate medical attention!

-Your Mable Team members, Chris Eijsbouts [CSO], Dr. Kumeren Govender [Chief Medical Officer]

What do you do with the DNA after testing?

Hi /u/Koboldsftw,

Excellent question! We do not retain your DNA sample after processing beyond what is necessary to ensure we've got the data (for example, if it needs to be processed again due to contamination or problems during extraction/sequencing). In terms of the data it is securely stored on our platform (in an encrypted and e-identified form) and only shared with service providers we rely on for processing. Beyond that, all of our data is stored in the US and not shared with any third parties without your explicit consent (for example, for research projects).

- Your Mable team member Tom Kent [Chief Technology Officer]

Looks really interesting! Question: how did you arrive at the SNPs you are using to determine what treatment is likely to work, and what validations have you done to show that they are really predictive?

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]

EDITED: For clarity

I usually have a headache every day, and have been getting them for at least 15 years and they're always worse during my menstrual cycle or if my head gets cold (which seems really weird). I've gone to the doctor and haven't received treatment that actually works well enough to be satisfied with. The most effective was Topamax but I lost too much weight and started getting terrible mood swings so I stopped taking it. I also have Rizatriptan for when they get too bad to handle and it works sometimes.

Have you researched ways things like diet, menstrual cycles, and climate or air pressure affect people who suffer from migraines?

Hi u/McPersonface_Person,So sorry to hear about your headache attacks. Mable offers multiple other individualized treatment plans to prevent migraine (without the use of Topamax) which could be effective.

We have also researched menstrual migraine and our telehealth partner physicians can diagnose and offer specific treatments for this.

We understand that diet, climate, or air pressure can trigger a migraine attack, and we have developed educational content available here (https://www.trymable.com/blog/migraine-diets-and-food-triggers) to ensure people living with migraine understand their personal triggers and risk factors.

- Your Mable Team Member, Dr. Kumeren Govender [Chief Medical Officer]

EDIT: Adding line breaks to make it easier to read.

I am interested in this from a data perspective, does the DNA test report back what specific genes I have that predispose someone to having migraines? Similar to how some DNA ancestry services allow you to access the raw data.

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]

EDIT: Adding line breaks to make it easier to read.

Does your approach include rarer types, such as hemiplegic migraines?

Hi @ u/DashofCitrus,

Unfortunately rarer types that cause one-sided weakness (such as hemiplegic migraines) will be identified as a neurological condition for further medical evidence. At this point in time, we are not taking anyone who has "red-flag" symptoms.

However, we certainly hope to help all people who live with migraine. So watch this space!! With time we hope to offer all migraine patients individualized holistic migraine treatment. There are many non-pharmacological treatments, such as Management of behavioral factors and Management of environmental factors. So for sure, there are resources on Mable that you may find beneficial.

https://www.trymable.com/blog

Your Mable Team Member, Tom Lovejoy MBBCH (MD)

Maybe it's Mabelin?

*applause*

Has your team done any research on vestibular migraines? How do you customize treatment based on genetic information?

Hi u/TartarControlDuff,

Thank you for your question. Vestibular migraine is unlike traditional migraine as the main symptom is dizziness and you may not even get a headache. As vestibular migraine is a complex condition, we are not able to provide treatment plans for this condition yet, however, we hope to look into this in the future. As for your second question: in practice, we customize treatment by testing whether you carry genetic variants that we know influence drug metabolism, in the sense that you would require adjusted dosages or should stay clear of medication to avoid side effects, and pairing you with a physician who can make treatment decisions while aware of this information.

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

What exactly in DNA have you found that links to migraines?

Are you able to find the exact types of migraines with this information?

Lastly, how far along are you with research to treatment?

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]

EDITED: Changed spacing to improve readability

Where do you believe the origin of migraines or even cluster migraines tends to originate? What are the most common causalities? What truly differentiates migraines from cluster migraines/headaches, or "just bad headaches."

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]

EDIT: Adding line breaks to make it easier to read.

Is there enough info about how migraines/headaches happen to really decide on a targeted solution? Most doctors I've talked to always seem to say they don't really how and why migraines happen.

Thankfully I've found a treatment that works wonders for me, but if I could have skipped the try this drug for 6 months, then this drug and the ups and downs that can cause especially when some of the drugs are antidepressants that'd be great.

Also How does the new treatments that are actually meant for migraines affect your plans? Like aimovig?

Thanks, u/hawkstalion,

I'm glad you asked. This is precisely at the heart of what Mable stands for. One of the main problems in standard migraine care is that a traditional clinical assessment rarely provides sufficient information about a person to narrow down the scope of potentially suitable treatments. As a result, people often undergo a long trial-and-error process trying to avoid side effects or to find effective relief.

This is why Mable helps physicians and patients bridge the gap between a traditional clinical assessment and the growing field of pharmacogenomics (https://pubmed.ncbi.nlm.nih.gov/22002450/). The number one thing missing in standard migraine care are biomarkers.

Lastly, monoclonal antibodies like Aimovig are part of our offering.

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

I'm curious what you may know about scintillating scotoma and the relationship with intense migraines.

Around quarterly I'll begin seeing floaters in one eye. It starts small and then over the course of 30 minutes or so it will mostly consume my vision where I can see very little. During this onset period there's no pain or anything. But after those 30 minutes the pain is intense with a great sensitivity to light. Also nausea. After things have subsided I still feel pretty terrible for a few hours.

Generally as soon as I see the scintillating scotoma I'll try to find a dark quiet place and try to fall asleep before the migraine shows up. If I'm able to, I can usually sleep through the migraine but still feel horrible afterward.

I've read a few things on the internet about others who have experienced this but saw your AMA and figured I'd ask if you've any experience with it?

Hi u/ThatGuyGetsIt,

Scintillating scotoma is a fascinating symptom, and is very likely linked to visual aura. I imagine it's really difficult to explain what it's like to someone who hasn't experienced it?!Aura is thought to be caused by a wave of abnormal nerve network firing across the surface of the brain.

This is known as cortical spreading depression (CSD). This is also thought to cause the trigeminal nerve to behave differently, This normally receives information from the skin of the face and the surface of the eyes. CSD may even cause the normally super-controlled Blood-Brain-Barrier to lose some of its structural integrity.

https://www.trymable.com/blog/what-is-migraine As you can probably tell, none of these are particularly helpful physiological processes, and its likely that there is a correlation with intensity of symptoms!

Luckily there are lots of treatment options that try to address the imbalance, both acute and preventative, pharmacological and non-pharmacological. (It's always worth making sure that there is no other cause for a visual field change and if there's any doubt seek immediate medical advice!!)

Tom Lovejoy MBBCH (MD)

(Source: Pathophysiology, clinical manifestations, and diagnosis of migraine in adults - UptoDate May 2022 (Cutrer et al))

EDIT: Adding line breaks to make it easier to read.

Me and my girlfriend both suffer from migraines, me very seldom and her rather frequent.

Out of experience I noticed that very stressful days are an important source of attacks, especially when the stress starts to go away.

How does that work? I expect stress to be a leading trigger or at least a major contributor, but a relief of stress seems a bit out of place!

Hi u/ItMeAedri,

Thank you for the question. According to a December 2021 study published in The Journal of Headache and Pain (https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-021-01369-6) , eighty percent of people with migraine self-reported stress as a trigger!

So you are absolutely right noticing that stressful days are an important source of an attack. It is important to know that often it's a change in baseline or routine activity that often triggers an attack, this means at both times while stress is increasing or while stress is decreasing could trigger a migraine. Hope this helps answer your question.

- Your Mable Team Member, Dr. Kumeren Govender [Chief Medical Officer]

The paper you linked by Hautakangas et al. found 123 associated loci with GWAS. I'm presuming you're looking at mutations at some of these loci as your markers for drug susceptibility.

My question: how much of the variance of migraine incidence do these loci explain? And what % of migraine sufferers do you expect will have a genotype that'll allow for a more targeted therapy?

Your site references a big increase in treatment effectiveness for patients on ineffective therapy – do you know how this would compare to patients changing medicines in a standard setting (w/o DNA testing)?

Thanks!

Hi u/Mometricsmoproblems, Glad you clicked through to the paper, it's a good read! The % of variance explained on the basis of the genetic associations in the 2022 migraine GWAS is about 10-15. Estimates from twin studies are much greater at 40-60%, and we're hoping that future genetic association studies will close this gap by e.g. looking at the effects of rare genetic variation on migraine predisposition.

Interestingly, there is evidence that markers from such studies of migraine predisposition work to predict drug response. See e.g. this really interesting paper by Kogelman et al. that predicts triptan response on the basis of migraine risk. That said, our loci of interest include those around well-known pharmacogenes (e.g. CYP450) which impact migraine drug metabolism without necessarily impacting your risk of having migraines.

Variation in these pharmacogenes, variation for which alternative treatment guidelines based on genetic information that exists, is really common. Here's a great overview that came out of Stanford on the prevalence of genetic variation impacting drug response, which also goes beyond migraine.

As for your last question, I haven't come across a mention of the expected increase in efficacy from a non-genetically guided drug switch in the literature, but the historic drug response data we collect would allow us to calculate this.

Your Mable Team Member, Chris Eijsbouts [CSO]

EDIT: Adding line breaks to make it easier to read.

My wife suffers from menstrual migraines that cause her to be completely down for about 3-4 days a month. Does your treatment work for this type? She currently takes sumatriptan with some success.

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)

EDIT: Adding line breaks to make it easier to read.

So in terms of your personalized medication, you use DNA to determine which particular medications such as sumatriptan, GCRP or some combination are best to use? I saw the pricing is $22/month… does that include the price of the medication? That seems much cheaper than the cost of sumatriptan or a GCRP would cost.

Hi, u/bignateyk thanks for your question.

Our DNA test is specifically built with preventative medication in mind. For acute medications, we can also help without the DNA test. You're right - the monthly price starts at $22. But, subject to your approval, it will depend on the specific individualized treatment plan for you. Some medications will increase the price, others will keep it lower.

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

If I already possess my full-genome sequence data (not a subset), can I skip the "take a DNA test" step by sharing my genome with you?

Hi /u/Techrocket9,

Thanks for the question. Ingesting data generated by third parties is definitely something we're looking to support in the future. Right now our pipeline isn't set up to accept this data (as you probably know, a whole genome is a LOT of data). Perhaps you'd be happy to DM us and let us know where you got your genome sequenced, and we'll look at accelerating that vendor in our pipeline roadmap.

- Your Mable team member, Dr. Tom Kent [Chief Technology Officer]

Any research into cluster headaches?

Hi u/shaft6969 Thanks for your question! Currently, we specialize in providing individualized treatment plans only for migraine, however, we hope in the future to expand to other headache disorders including cluster headaches.

Your Mable Team Member, Dr. Kumeren Govender [Chief Medical Officer]

EDIT: Adding line breaks to make it easier to read.

I understand they're different beasts. One at a time. Good luck!

Thank you! Wishing you all the best.

EDIT: We quoted the wrong text here.

Won't the most severe migraine trigger turn out to be the astronomical cost of the treatment for the patient?

Hi u/curtyshoo,

Thanks for your question. Our mission is to provide people with a more efficient and cheaper alternative to get the treatment that actually works.

Mable's price is well below the average cost of finding effective migraine treatment: under current standard care, it often takes several attempts to find a treatment that works (in some cases years), which costs up to $4K for avoidable MD visits and unnecessary medications.

As such, we are aiming to provide migraine care that is not only more affordable but also more effective than the current standard approach.

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

EDIT: Added line breaks to make it easier to read.

Thank you for this Reddit visit!

My question: is there a significant link between gut microbiome, DNS, migraines (or cluster headaches), and food allergies/intolerance?

I ask this because i know 6 women who:

• Suffered multiple migraines per week

• Are not lactose intolerant (tested via blood glucose)

• Were daily milk drinkers until discovering abstaining practically eliminated their migraines

• 5 of them have children, all of which have milk allergies to the point of getting hives and forcefully ejecting the milk.

  • I'm the 6^th, but I'm child-free.

I realize that anecdotal evidence is not worth the air it's said with, but I found it notable when all 5 people I've known with the milk/migraine thing I have had children with lactose allergies.

Thank you :)

Hi u/girlpockets ! Great question, is there a significant link?! Unfortunately, nobody knows for sure! There are many diets that appear to help people to avoid migraine attacks, and improve migraine symptoms. However, there is no consensus on which is the best diet for an individual patient.

It's an area we are really interested in, my last position as a doctor was helping people to eat more healthily! Our advice would be to keep a food log and monitor other Food and Drink Triggers. Make sure your diet meets US guidelines eg https://www.dietaryguidelines.gov/.

As everyone is individual it's hard to give a one size fits all approach. Lots of people avoid dairy but ensure your intake of calcium and protein is found in other sources. There's also really scanty evidence for us to propose the best diet for patients (right now...)

Also, consider Mable, we consider Individualization and Holistic care as much a part of treatment as medication! Certainly, we hope to help patients with the Management of behavioral factors and Management of environmental factors, as well as a Tailored pharmacological approach.

-Your Mable Team Member, Dr. Tom Lovejoy

(Source: American Migraine Foundation, “Diet and Headache Control.” https://americanmigrainefoundation.org/resource-library/diet/)

EDIT: Adding line breaks to make it easier to read.

My husband found this thread for me today, and it's a literal miracle. I've had migraines for the past 7 years , they've gotten worse. What I have worked out is that it's mostly menstrual, but I think weather affects it as well (high/low pressure systems). In any case, I just finally got in to see a neurologist in February, only seen her twice so far. I'm on rizatripan and promethazine, and now I take them before my cycle starts. It's mostly been working, seen dramatic improvement, until Monday. I had the worst migraine of my life. Like I wanted to walk into traffic bad, just to make it stop. I spoke with my neurologist, but essentially they want to "wait and see" f this happens again. So if a massive one like this happens again, I'm SOL and will be without anything to make it stop.

​

I see the AMA here today and try to sign up, like I was at the payment screen to pay for the kit, and it said that Mabel isn't available in my area yet. Do you have a rough roll out date for Washington State? Also, if I signed up but it isn't available , am I still on a waiting list?

​

I'm s grateful you guys are here, I hope to get signed up soon. (I'm also sure there's lots of traffic today, so I will check back)

Hey u/CrimsonGalaxy,

We feel you here. It is highly frustrating for your neurologist to want to “wait and see,” as waiting so long to see them and potentially trialing a lot of medication for 6-15 months is not fun.

The wait to see a neurologist or headache specialist can be extremely long. One of our Medical Board members, one of the top headache specialists in the United States, Carolyn Bernstein, has a 9-month wait to be seen. Combine the wait with the wait and see; it can take 1-2 years or more to get lasting relief.

This is what Mable does differently: individualizing your treatment based on your DNA. Carolyn told us one of the missing critical things in migraine treatment today is biomarkers. “When we capture predictors of how a person may respond to a treatment, that leads to more informed treatment,” says Bernstein. We’ve combined the treatment processes of top headache specialists with using your biomarkers to inform treatment individualized to you.

For your question on when we’ll roll out to Washington State, we’ll be available in Washington in less than three months, and you are now on our waiting list after signing up. You might have hit a bug here, so we can help you get sorted out if you DM us.

- Your Mable Team Members, Bobby Huang [Chief Growth Officer], Dr. Roman Rothaermel [CEO]

Where are you guys based?

Hi u/ursugardaddy6996,

We're based in London, but we will be available to most of the US before the end of the year!

My partner is struggling with an extremely long-lasting case of dizziness (months at a time) that doctors we've visited believe may be migraine related. She's currently on Topamax and it doesn't seem to be helping at all. Are there other options for addressing this vertigo and might this be a route to take?

Hi u/koliano,

I'm sorry to hear about those symptoms. Dizziness and vertigo are particularly difficult symptoms to live with. Migraine with aura is often linked with vertigo (the sensation of spinning/ moving) although there are other causes, as other doctors have likely discussed with your partner. It's unusual for dizziness to persist for months, so I wouldn't be keen to guarantee a diagnosis, or give you specific medical advice over Reddit!

Topomax is probably the most widely prescribed medication for preventing migraines. It can work well for those who have aversion to light during migraine (photophobia or photosensitisation). However, Topamax has many side effects that affect the brain and nerves: eg dizziness, drowsiness, fatigue, impaired coordination, balance and/or speech, memory impairment, anxiety, behavioral problems, depression, disturbance in attention, lack of concentration, mood disorder, nervousness, psychomotor impairment, language problems.
If dizziness is due to migraine, it may improve with more time with Topamax, as preventatives take up to three months at optimal dose to have full effect. However, dizziness is a known side effect of Topamax... So again, I wouldn't like to make suggestions here! There are many other preventative medications which don't tend to cause dizziness and vertigo symptoms, so may be worth looking into.

I hope this helps!
- Your Mable Team Member, Tom Lovejoy MBBCH(MD)

As a migraine sufferer I would be interested in this, how would I go about having my MD set this up?

Hey /u/Omegaprimus,

Thanks for the question! There's no need to have your MD set this up at all! Mable is all online and our partner physicians handle the individualized prescriptions for you. We will then arrange for your medications to be delivered directly to your door - on a regular schedule so you never run out. Of course, you can always discuss the proposed individualized treatment plan with your MD in addition to that.

- Your Mable Team Member, Dr Tom Kent [Chief Technology Officer]

I (28f) have migraines almost everyday that are so serve it ruins my life. I have been on and I am still on different beta-blockers to treat this. This treatment seems to be going no where for me but it seems the be the only solution that has been given to me by the hospital I attend.

My late mother had a disease with inflammation on/of the brain and she was the only one at the time on Ireland , uk and america to have it. Because the doctors I have spoken to do not know what this is, this is why I have been just put on painkillers and beta - blockers.

Is there anyway Mable can help?

( If I can spell it how it sounds , the disease was called idiopathic - meningeal - fibrosis )

Hi u/NoodleBrainzz

I'm sorry that your migraine days are making life difficult at the moment. Migraine can be a truly debilitating condition, and you're not alone in feeling this way. Aside from medication and genetics for a moment: migraine affects everything - I hope you have some support, or you're able to ask friends or family to help you through this.

Beta-blockers are often used as a preventative medication for migraine. However, there are many other treatments available to prevent migraine days apart from beta-blockers that may be better suited for you. The clinical team can assess you to see if Mable's treatment plan is the right fit for you.

Regarding Idiopathic meningeal fibrosis, as you said it's rare. Rare conditions in medicine tend to have less data to say what causes it, who gets it, and what should guide treatment options. Idiopathic means no cause could be found. (From Greek ἴδιος idios "one's own" and πάθος pathos "suffering.").

If your migraine days are caused by idiopathic meningeal fibrosis, this makes it a secondary headache. The fibrosis is the inflammatory condition as above. Currently, Mable does not treat patients who have migraine due to another medical condition, so it would need to be excluded before we could.

I hope this helps! ps great username

Your Mable Team Member, Tom Lovejoy MBBCH(MD)

(Pathophysiology, clinical manifestations, and diagnosis of migraine in adults - UpToDate May 2022
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200046/)
(https://ichd-3.org/1-migraine/)

What causes some people to have migraines and other people to have no head aches at all?

Hi u/Lovelyterry,

Why some people are predisposed to headaches and migraine attacks is partly genetic, partly acquired, and partly unknown! There are likely to be contributing factors predisposing to migraine, or absence of mitigating factors such as genotype, and how it displays itself as migraine, or headaches from other causes. This is aka phenotype. Then there are likely to be external influences that affect migraine from beyond a biological and psychological origin (media, social, economic, food, activity, infrastructure, developmental, etc.) When someone has the genotype and accumulates risk factors, the likelihood of migraine increases. (With headaches it depends on what is the cause so I'll focus on migraines!) Other people either don't have the genotype that leads to migraine, or their lifestyle/ environment doesn't trigger symptoms. AKA the lucky ones.
In many people living with migraine, there is a problem with the membranes that surround and protect the brain. These membranes are called meninges and are sensitive to pain, in much the same way the membranes of the eye can be irritated by dust or chemicals. This makes our eyes itch and become inflamed, a natural healing response.

On a migraine day, there is an activation of pain reflexes in the nerves supplying the meninges. The nerve most affected is the trigeminal nerve which responds by releasing pain- and inflammation-causing chemicals. This inflammation results from changes in the blood vessels in the brain, making them relax (the more accurate term is dilate).

In the healing process, inflammation allows our immune system to fix a cut, or fight a bug. In migraine however this inflammation is not helpful, it causes redness, heat, swelling, and pain, caused by certain proteins and chemicals leaving the bloodstream and surrounding the nerves.

As a consequence, the trigeminal nerve continues to sense pain even after the initial migraine trigger has passed; this inflammation can persist into a long-standing or chronic state. This is believed to cause increased sensitivity to pain and making further migraine attacks more likely to happen ie chronic migraine or difficult to manage migraine. Some medications reduce or block the production of one of the chemicals called calcitonin gene-related peptide (CGRP) that acts on the blood vessels to cause inflammation in the coverings of the brain. CGRP receptor antagonists, which include drugs like rimegepant, work to stop the binding of CGRP preventing inflammation. With less inflammation in the arteries and in the brain, there is less redness, heat, and swelling. This can reduce the level of pain that a patient experiences. This in turn helps to relieve migraine symptoms once a migraine starts to appear.

I hope that answers your question!

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

EDIT: Added spaces to make it easier to read

How many migraines per month are required for treatment by Mabel? Many treatments are only recommended for 15 or more per month, for example, but I only have a few migraines a month (despite that being a few too many, in my opinion).

Hi u/PuzzleheadedLet382, thank you for your question! Mable supports people with migraine irrespectively of how many migraine days they have.

Depending on your migraine frequency, intensity, and your interest in preventative medication, Mable can offer different types of treatment plans for you. For example, our DNA test is built with prevention in mind, but other non-DNA-guided treatment plans are also available.

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

EDIT: Adding line breaks to make it easier to read.

Have a friend who has been suffering from a 6 month migraine. She has tried every medication under the sun, Botox injections, brain scans, ice packs, diet change etc… with no relief. Also no diagnosis. Has seen PCPs and a neurologist. Why should be next steps to escalate her care to get answers and relief?

Hi u/cowboys30,

Thank you for your question. We're so sorry to hear that your friend has a really complicated type of headache. Unfortunately, we have only developed treatment plans for uncomplicated migraine currently and would urge that your friend contacts a neurologist or specialist headache physician again to evaluate and treat this headache.

Here is a useful tool to help find recommended headache physicians in your local area: https://americanmigrainefoundation.org/find-a-doctor/

- Your Mable Team Member, Dr. Kumeren Govender [Chief Medical Officer]

How's it going?

Hi u/Salt_Tumblewee,

Pretty good! How are you?

Are you able to detect potential triggers, or is it only drug response?

Some background: I get 4+ migraines a month, respond well to rizatriptan, have had limited success with beta blockers & topamax, currently on a magnesium/riboflavin supplement.

Hi u/tapo,

Appreciate the background, and am glad rizatriptan has been working for you! We do collect data on common riggers (e.g. dietary, sleep) so that we can detect which ones are problematic for you. In the long term, it'll be interesting to see whether sets of triggers define migraine subtypes that have unique treatment needs. This type of clustering requires a large dataset to do robustly! What has your experience with the magnesium supplement been like?

-Your Mable Team Member, Chris Eijsbouts [CSO]

You mentioned that you are generally focusing on drug response in your studies. Are you also looking into the length of time (or likelihood) before patients habituate to different medications?

Hi u/pre55ure,

You're right, our primary focus is on symptoms severity and side effects. We haven't yet looked at habituation, but it is on our radar along with the identification of factors relating to medication overuse (whether genetic or not)! Large, externally collected datasets generally lack data on treatment response that would be detailed enough to cover habituation (treatment persistence, as a proxy for efficacy, is more common in these large datasets), so I expect the data we collect will be important here.

- Your Mable Team Member, Chris Eijsbouts [CSO]

My wife has suffered for 20+ years, she needs relief. Has tried most meds and does Botox 4 times a year, 20+ days a month, can you help?

Hi u/kcjnz,

Thanks for the question. Yes, might be be able to help! Mable provides individualized treatment plans for migraine, and our partnering telehealth physician network would take into account all your wife's previous treatment information to understand what went wrong with her initial treatment.

Newer medication such as Nurtec (an oral calcitonin gene-related peptide (CGRP) antagonist) for preventative treatment of migraine might also help if other treatment has failed.

-Your Mable Team Member, Dr. Kumeren Govender [Chief Medical Officer]

How do we start the process? Thanks for your reply.

You can begin the process here: https://www.trymable.com/quiz/dna