Ask the Mito Doc – December 2025: Wrapping Up 2025 with Our Mito Docs
All answers today are based on personal experience of the participants. As always, please consult your personal physician prior to taking any action.
Speakers:
- Gregory Enns, MD, Stanford Medicine, Palo Alto, CA
- Bruce Cohen, MD, Akron Children’s Hospital, Akron, OH
- Jaya Ganesh, MD, Icahn School of Medicine at Mount Sinai, New York, NY
- Matthew Snyder, MD, University of Virginia Health, Charlottesville, VA
Q: Is there anything new in terms of the Mito cocktail? What are your thoughts on it these days?
A: Gregory Enns, MD: I typically recommend what has been published by Mitochondrial Medicine Society with full realization that everybody does things differently. I focus on Coenzyme Q10 in its ubiquinol form, which I think has better distribution throughout the body. There are two basic forms of Coenzyme Q10: One ends in OL and one in ONE, so ubiquinol and ubiquinone, and I tend to focus on the ubiquinol for formulation. Then there’s a recommendation for riboflavin, which I’ve always found very interesting. I have no doubt that riboflavin is important, but I’m more of an advocate for all the B vitamins, so as long as riboflavin is being given in addition to thiamine and other B vitamins easily in a tablet like a B50 that’s typically what I recommend. And the other recommendation was alpha lipoic acid as a sort of a mitochondrial membrane stabilizer seems reasonable to me as well. Those are the basic things. I look at carnitine levels and supplement if deficient. I’ll consider creatine if there are muscular symptoms. And for those especially who have mitochondrial DNA deletions, supplementing with folinic acid is something I think is fairly standard. As far as what’s in the future, I don’t know, but I’m very interested in epicatechin, which is a component of some of my favorite foods: Dark chocolate and green tea, and it’s a mitochondrial biogenesis agent that has also been purified and is going to be studied, at least we’re going to be doing some experiments next year at our institution, looking forward to that. As far as what other people do, I’m really curious as well, because I’m sure we’re all a little bit different.
A: Jaya Ganesh, MD: Sure, I completely agree with Dr. Enns, and in fact, I’m very grateful that my cocktail is very similar. Over the last few years, I’ve gone to reach out to creatine more, particularly for my patients who’ve had cardiomyopathy as part of their mitochondrial diseases. I think it’s variable, and it’s patient-to-patient. I would like to know more about nicotinamide riboside, the active form. I saw some literature, and I’ve seen some presentations that it’s doing well, and I think there is some trial trying to study this formally in male patients so I’m holding out for some concrete data to come out before I start patients on this because it’s extremely expensive. But if I had a patient with the correct lesion that I think that would benefit from that, that is something that I would be willing to try. I also feel that the Super B50 is probably easier for the patients to take and also on their wallets, because giving each vitamin separately seems to be very difficult. So my cocktail is usually Coenzyme Q10, ubiquinol, B50, making sure that biotin is part of that, riboflavin, thiamine, and niacin, of course. Alpha lipoic acid is a bit out of reach for many of my patients because of the expense, but if they can, that’s something that I recommend.
I want to make a pitch for nutrition, because there are patients of mine, pediatric patients, who’ve come in with frequent seizures, stroke-like episodes, la-la-la-la-la, and then you get them in, you convince the parents and the team that a G-tube may be the way to go, and you start to feed, and they blossom. And they’ve completely stabilized, their growth is good, they’re actually gaining some milestones, and it’s real. In fact, I just had a conversation with a MELAS patient 2 hours ago saying that maybe we should think about a G-tube because he was behind his hydration, he did not want to take his meds and presented to the ED with multiple seizures. And then the next thing was, does he have a stroke? Do we have to give arginine? Do we have to give this? And the only thing he wanted to eat was sushi, and we got him sushi, and then we actually were able to discharge him, it was just seizures because he missed his meds. So, nutrition is such a huge thing in these patients. And just to mention about sleep, some of my mitochondrial patients, particularly the adolescent teenagers, are having insomnia, sleep disturbances, etc., and this is going on for days at a time, and that is registering as seizures, it precipitates some other event. So we’ve actually tried melatonin, we tried the standard drugs. Some of the seizure medications are also a little sedating. They help, but we’ve had to reach out to our colleagues in psychiatry for more heavy-duty medications to help them with their anxiety and some of those phenotypes the side effects of some of these medications is weight gain, and so it’s always one step forward, two steps backwards with these patients. So some of those general medicine, general pediatric care is also very, very important in their management.
A: Bruce Cohen, MD: So I agree with what’s been said. I started out my career when my two mentors in mitochondrial disease gave me a cocktail for my patients. There were about 20 supplements long. There wasn’t enough room in the children’s stomach for food. My patients were being given so many pills. The 2012 review of the literature that’s been repeated again in subsequent years, shows that there’s no clinical studies that definitively show improvement using these supplements. So I have discussed this with my patients. I have some patients on no supplements and some patients are on the same supplements that Dr. Enns listed earlier. So I think it’s variable, and it’s a patient-to-patient decision. I don’t insist my patients go on supplements. If they’re interested I certainly will put them on these supplements.
A: Matt Snyder, MD: My approach is very similar to Dr. Cohen’s. I’m sure we all have a candid conversation with each one of our patients as we don’t know if this is going to help but it may. The conversation I usually have is, if you derive any benefit from it, keep taking it. If after 3 or 6 months you don’t see an improvement in anything, then it’s up to you to consider whether you want to keep spending money on this product, whether we’re doing it one at a time, or we’re doing multiple things at once. I think my hope is that in the future we will continue to develop more biochemical tests. The glutathione that’s out there, that’s one thing I’ll typically send on most of my patients to Stanford, and if the glutathione is low, consider adding certain supplements with that. But my hope is as time goes on, we’ll have more ways to say, for this patient, this specific type of a supplement is better suited than that other, rather than trial and error with every patient. To Dr. Ganesh’s point about nutrition, and for the patients that can engage in it, is physical activity. Nutrition and physical activity I think there’s stronger evidence for both of those in our community than there is for a lot of the supplements that we talk about, and so if you’re able to engage in any physical activity it may be beneficial.
Q: Is there a possibility of a tailored FDA-approved mito cocktail? Do you ever think that will happen? Do you ever think there’ll be a clinical trial for any of the supplements?
A: Bruce Cohen, MD: Not one that’ll be approved by the FDA. These trials are incredibly expensive to run. And when you’re talking about riboflavin dosing costing 5 cents a day, I just don’t think it’s going to happen.
A: Greg Enns, MD: Yeah, one of the issues is these supplements are widely available, or most of them are so widely available that people are already taking them, so it’s very difficult to come up with a randomized trial where you have the blinding, some people are taking some things, other people are taking others, and the duration of time that would be needed would be prohibitive, so I think it would be theoretically possible, but in practical terms, really hard to do.
Q: How do you define the S in MELAS? What constitutes and defines stroke-like? The hemiparetic episodes that affect facial muscles, arm and leg weakness, numbness? Can there be subtle signs that would still be considered stroke-like episodes? Does the qualification require permanent bodily damage? Would MIDD + count?
A: Bruce Cohen, MD: I think the important term is stroke-like. Because there’s certain things that really don’t look like strokes in these stroke-like episodes. A number of patients fully recover if their MRI scans recover completely and quickly, as well as their neurologic symptoms. Whenever we see a patient with a MELAS stroke-like episode, we hook them up to continuous video electroencephalogram, that’s brainwave testing. And a number of patients have been in what’s called subclinical epilepticus. In other words, it doesn’t look like they’re having a seizure on the outside, it looks like they’re having a stroke, but inside their brain. That portion of the brain is having a seizure. And when we treat with anti-seizure medicines, high-dose anti-seizure medicines, which tend to be such high doses, we put the patients to sleep, when the seizures get better, the strokes get better as well. So I think some of us are thinking that a lot of these stroke-like episodes are, in fact, seizures that just go unrecognized. And again, a seizure that goes on for a long time can result in permanent brain injury, also known as a stroke. So I’m just going to throw that out there for my colleagues to criticize the thought process, or support it, or whatever.
A: Matt Snyder, MD: I usually consider the stroke-like episodes to refer to brain MRI changes that are found during the neurological changes/episodes that don’t follow a typical stroke-like pattern on brain MRI. Stroke-like episodes can be seen in some other mitochondrial diseases and are not just limited to MELAS. As a biochemical trained geneticist, I didn’t realize the connection between seizures and epilepsy and MELAS episodes until the UMDF conference this summer. Everyone was in a room and really discussing this, because where I trained we thought all about nitric oxide and nitric oxide precursors, and giving IV arginine immediately once kids or adults are admitted. We didn’t generally hook them up to EEGs, but hearing that side of things, and hearing in Europe there’s not as strong of an emphasis on the nitric oxide hypothesis in MELAS, and IV arginine isn’t a benign product that we’re infusing into patients on a regular basis. So it’s really thinking about the cost benefit of the treatment that we’re giving patients when they show up. Having a stroke-like episode. So that’s why I chuckle, because I was trained to think in one way and quickly in the last year, I’ve learned that there’s more to the picture that we’re learning.
A: Jaya Ganesh, MD: I completely agree with Matt. We were very, very clear that if you have MELAS and if you had a stroke-like episode, you gave IV arginine, and that was one of the few things that it was pretty standard and knowledgeable until the papers that came out a couple of years ago, followed by the discussion at the UMDF. I think we had a sidebar discussion with some of the neurologists in the group, and I think what came out was that, yes, seizure is probably the initial event, but subsequently there is a metabolic change in the brain tissue, there’s some hypermetabolic states, some brain hyperfusion to put it in standard terms. The brain needs a little bit of extra blood flow, its metabolic activity is increasing, so maybe arginine is beneficial in those situations. So we decided not to change our policies radically in what we’ve been doing, particularly when it comes to MELAS in a patient with acute stroke. But as Matt said, we are definitely being very diligent in excluding active seizures and making sure that the seizures are addressed right away. So all these patients are brought into the ED, Neurology, we talk to them, we educate them on the importance of getting on top of this. And then we support them with arginine as needed. And patients are on maintenance arginine or citrulline as well. And personally, I’ve been asked, consulted on patients who have mitochondrial disease outside of MELAS and who come into the hospital with seizures, and they’re on 3, 4 anticonvulsant drugs. Everybody’s at their wit’s end, seizures are not stopping. Beta focal seizure or a generalized seizure. I’ve given them IV arginine bolus and treated them with the arginine infusion, and have seen some response. Now, you can ask whether it would have happened anyway, because this is already day 3 or day 4 after the acute event, or whether we did something positive. The answer is we don’t know. So, we as a group here at Sana, we just decided we are not going to change our practice radically but we are cognizant of the fact that the seizure control is really the key in the acute phase. So, still looking for more data, more evidence.
A: Greg Enns, MD: I agree with whatever has already been said. I was fascinated by the discussion at the meeting in St. Louis related to the differences of use and opinion. As far as acute Arginine in stroke-like episodes we had a similar thought process to Dr. Ganesh, we’re continuing to use IV arginine as an acute measure. I am still not very clear as to the best outpatient regimen, whether it’s arginine, citrulline, a combination of both. I understand that Dr. Scaglia has been doing quite a lot of work in this area. And it’s found that perhaps very high dosing of citrulline has the potential to generate some compounds that might be toxic, and we should be mindful of that, but in the dosing of citrulline and arginine that we typically use should be quite safe. So, I’m not sure what the best way forward is. We do need more experience but in the meantime, we are doing very similar things. We’re still treating stroke-like episodes with intravenous arginine in an acute phase.
Q: Could you speak to the current research landscape for MELAS? Are there any active clinical trials or recent studies that show promise for treatment or management?
A: Matt Snyder, MD: This is the most advanced phase trial at this point. Not currently recruiting, but hopefully phase III study will be recruiting new patients soon. https://clinicaltrials.gov/study/NCT06402123?term=zagociguat&rank=1
Q: Is there a connection between mito and cataracts?
A: Matt Snyder, MD: Yes, there are connections between mito and cataracts.
Q: Are there any new treatments for ataxia in mitochondrial disease?
A: Matt Snyder, MD: There aren’t any new treatments yet for ataxia in mitochondrial disease, but hopefully these recent drug approvals will lead to more development!
Q: Is a cheek swab needed if muscle biopsy was negative?
A: Matt Snyder, MD: If muscle and blood are both negative, then cheek swab might not be necessary. But as Dr. Enns said, every tissue may have a variable level of mtDNA change.
Q: Can to speak to GDF 15 and cardiac enzyme Troponin tests for Mito markers?
A: Matt Synder, MD: Yes GDF15 can be a non-specific indicator of mitochondrial disease. Right now, I’m not aware of specific therapies or supplements that are helpful to target elevated GDF15.
Q: So are you saying that you no longer believe the 40-60% yield quoted in papers for mito detection rate now that we have WGS? (i.e. that that many patients won’t be able to find a genetic answer due to testing/knowledge limitations)
A: Matt Snyder, MD: I think that is still a good estimation right now. The question is how do we detect the other 40%? Is it due to things that we can yet detect in the DNA? Is it due to a different primary condition that is leading to a secondary mitochondrial dysfunction? This is a big question that still needs to be figured out!
Q: Should I be using Sildenafil in my younger child?
A: Greg Enns, MD: I’m not really sure. I think I need to know more about it and its mechanism of action whether it would be appropriate in this specific situation, or whether it’s more appropriate to help ophthalmoplegia, maybe older patients, maybe not. I think a specific question is, is anybody else using Sildenafil for any of their patients, and a more general question would be, how do we all approach these sorts of issues, because I think more and more this is going to happen where there’s a novel medicine or a repurposing of a medicine that we can potentially use to be helpful, but how do we approach it with our patients.
A: Bruce Cohen, MD: My partner has started a few patients of his with mitochondrial DNA point mutations on Sildenafil. Too early to tell they’re stable. But these kids have really no side effects of the medication. Obviously, this is the drug that is better known as Viagra. The side effect profile is well known and well tolerated. So, I think the story’s too early to tell. I’ve had conversations recently with Mary K. Koenig, who probably my guess has lots of patients on Sildenafil. I think this story’s probably going to evolve over the next year. There was a wonderful piece on 60 Minutes a few days ago on the cost of these new emerging genetic therapies. I encourage people to find it online and listen to it, it’s a beautiful story.
A: Matt Snyder, MD: And I think to speak to somebody’s question in the chat about there being a huge mismatch between the cost of emerging therapies and coverage, the idea of drug repurposing even though some of these drugs that we’re talking about being repurposed can still be quite expensive. Drug repurposing can really help meet the needs of this cost-to-coverage imbalance that we see in the rare disease space. Any time that we can find some of these drugs to repurpose, it’s really exciting, especially in the metabolic disease community, we have a number of those drugs that have been repurposed, and now to try to do the same in the mito space is important because of the cost of the new therapies that often are developed.
Q: What are your thoughts on gene therapy for mitochondrial disease?
A: Greg Enns, MD: I think gene therapy in general is finally progressing for a certain number of conditions. The issue with mitochondrial disease for many patients, of course, is that it’s so widespread throughout the body, in the brain, in the muscle, and these are particular areas that are very difficult for gene therapy to correct. The initial successes and the focus of gene therapies, and for that matter messenger RNA therapies, they’re also being developed for genetic diseases, have been focused on areas where there the organs involved are relatively more straightforward to treat. So, it’s easier to get a gene therapy vector in the liver and in the bone marrow, for example, then throughout the muscle, or into the brain widely. So I think as we have more successes in gene therapy on the target areas that have been successful, like the liver and bone marrow, and as gene therapy vectors are developed, the delivery system for the gene that are able to enter the brain and spread the message throughout the brain, as those are developed and shown to be safe, I think that this will be progressing very well in addition to all these other treatments we’ve discussed. So, a bright future there for these therapies. And a bright future, I would say, for also things such as stem cell therapeutics and other areas that are being investigated. I get asked this question quite a lot. And I don’t see it as something that’s going to happen tomorrow, or it’s not necessarily, as I say, ready for prime time right now. But the hard work is being done to make these types of therapies possible for the future, so I think science is progressing, and there’s every reason to remain hopeful.
A: Jaya Ganesh, MD: My own experience is limited, and it’s limited to another group of diseases called lysosomal storage diseases, where we have some studies that are active. And it works in that you give a gene to make enzyme that the patient is missing, so to that extent, the gene is able to code and make the enzyme. So, but the ultimate question is, is this enzyme processed appropriately, and does it function appropriately in various systems? And comparing lysosomal diseases are also multi-organ system disorders. But between the two, I would say that the mitochondrial diseases are far more complex and affect organs like the heart and muscle and the brain, which are pretty resistant to access even for these therapeutic interventions. Again, not tomorrow, but I’m hopeful. I have a feeling that some of the other mechanisms, like stem cell therapy or small molecule therapy may actually beat gene therapy to the finish, and they may actually prove to be more beneficial. And I’m really hoping that that’ll be the case.
A: Matt Snyder, MD: I think the only addition I’ll make is that pretty early in my career so far, I’ve learned to not say never. I think the speed of some of the gene therapies that we’ve seen in the last year or two, even with the base editing that’s gone on at CHOP with a patient with a urea cycle condition really changed my thought on FDA approval, getting people disease-modifying therapy quickly. It just gives me hope, still, for the future, that there will be many therapies for straightforward diseases to treat that we’re talking about, and for the mitochondrial disorders that affect every organ system that really are a lot more complicated, to think about when it comes to treating from a gene therapy approach after a child has been born.
Q: My genetic testing came back with nothing, should I consider reanalysis? And if I do, how often should people do reanalyze their genetic testing?
A: Matt Snyder, MD: So where we are now with our genetic testing is it’s really, really good, at least if you’re getting broad genetic testing for the first time. This year, most of the individuals that I’m seeing in clinic I’m either getting insurance approval for whole genome sequencing, which includes mitochondrial DNA of either the blood or of the skin tissue from a buccal sample, so when you take a cheek swab and we re-swab your cheek and insurances are either paying that, or the lab are competing hard enough with each other that they are depending on what insurances that you have. They’re willing to eat the cost for some institutions if insurance does not cover it. Most of these companies have really good financial assistance programs that we use with patients. If you make under a certain threshold your out of pocket maximum cap at $250. Broadly speaking, whole genome sequencing, now that it is here, is a fantastic test if you have multiple medical issues that could fit into the bubble within mitochondrial disease, and I think that there still is if your testing is completely normal or negative. We’re still learning more and more each year, and so there’s still reason to reanalyze that, I would say every 2 to 3 years. The longer time goes on, the less likely we’ll find more if we keep reanalyzing, it’s that our testing will probably just continue to evolve and get better. So, in short if you haven’t had whole genome sequencing, or whole exome sequencing plus mitochondrial DNA I think that’s the best test that I’m doing for my patients. And if your testing is normal, or negative, or has a variant of uncertain significance that we really can’t do much biochemical testing to help resolve, then reanalyzing every 2 to 3 years. But if we have a variant of uncertain significance, especially in the mitochondrial disease space, there is some more testing that we’re often able to offer to at least help move the needle in suspicion. We can’t always prove definitively, and there may be more that your physician may recommend after a whole genome sequencing is resulted.
A: Greg Enns, MD: 2 years is a good time frame I think, it’s one that’s generally practiced. The reason is that I think it’s important to also understand all those genome sequencing people called whole genome sequencing. Genome sequencing is a very modern and excellent way of interrogating, analyzing DNA, and finding genetic variants that could be responsible for causing a disorder. The genome sequencing that we do in the clinic when we send it out to a lab is only going to be as successful at detecting things as our current knowledge, and our current knowledge is always changing. We’re having more genes that are related to human disease found every day, every week, every month, every year, so that’s part of the process. It is not that the sequencing has necessarily changed so much. But our knowledge has changed, and we can now focus on other genes that have been discovered that also cause a similar type of clinical finding. So that’s one of the reasons why we ask for reanalysis.
A: Bruce Cohen, MD: I agree to everything that’s been said about whole genome sequencing. I think that’s the state of the art right now. But we need to not forget about common diseases that can make a mitochondrial disease worse. I’ve seen patients referred to me for mitochondrial evaluation who had severe vitamin D deficiency, severe iron deficiency, and horrible sleep apnea, that when they got put on CPAP had enormous improvements. One patient who had a blood glucose of close to 500, the physician forgot to check a basic lab was mimicking diabetes and diabetes mimics the ravages of mitochondrial disease and vice versa. So I think it’s incumbent that you get checked for common illnesses, and the last one is B12 deficiency and thyroid disorder. So I’ll stop there.
A: Jaya Ganesh, MD: We recently had a patient who was in their mid-30s, did very poorly after having been placed on statins. And so statin myopathy, which you get for hyperlipidemia, that’s a very important mimic of mitochondrial myopathy, and I’ve had patients who have done better after the statins dose was reduced or changed to a different product to help control their blood lipid. And I also had a patient who was diagnosed with TK2 deficiency because he came to us for evaluation of statin myopathy and rhabdomyolysis. So I think it goes both ways. And some of my older patients and patients who’ve not been seen in clinic for the last 7 to 8 years in any metabolic or genetic center, but who’ve carried a diagnosis of mitochondrial disease, developmental delay, intellectual disability, have really turned out to have another static encephalopathy, another newly described gene defect, and that has really important implications for their own future. Some of them are reproductively fit, they can go on to have children. Some of these disorders are dominant, so I would recommend that if people have not had a comprehensive genetic testing in the recent couple of years, I would definitely go back to your physician and have that done. And there is that difference between exome sequencing and genome sequencing, because exome can still miss, and to date, the best that we have right now is genome sequencing and the mitochondrial DNA being looked.
Q: What is the clinical difference between buccal swab results and urine sample testing for 3243A/G? My cheek swab was 27 percent, all 3 sons over 93 percent in urine. What does all that mean?
A: Matt Snyder, MD: We know that in MELAS, the heteroplasmy level, or the amount of the DNA, can diminish over time in the blood. The cheek swab, depending on what lab you send to, and depending on who you learn from, the cheek swab we think is more of a better proxy of white blood cells. Some will say we get a mix of skin cells in there as well, but with your cheek swab or your blood, I’m not surprised if my MELAS patients that are in their 30s, 40s, or 50s, have much lower levels of heteroplasmy in their blood or their cheek swab than they do in their urine. Clearly you’re seeing a fantastic mitochondrial disease specialist to even check the urine to make sure that the urine was higher, because we think that the urine heteroplasmic level, or the amount of the DNA change that we can detect, in urine is really one of the best proxies we have to what it’s like in muscle. And we know that the urine level doesn’t change over time, and getting a urine heteroplasmic level is a lot less invasive than doing a muscle biopsy to confirm whether or not you have enough of this DNA change that we need to really be concerned about.
A: Greg Enns, MD: Just that this is not unusual. There’s going to be different amounts of heteroplasmy, or some people say mutant load however you want to say, where there’s a mitochondrial DNA abnormality in the body, in different tissues, and that’s just one of the basic biological premise in mitochondrial disorders that are caused by mitochondrial DNA. And so it’s not unusual to see things different in different tissues. It’s relatively common. And what that exactly means is going to be also variable for each patient. So, 93% mitochondrial DNA findings in urine, and to be clear, it’s not the urine, you’re having cells that are being taken away from the kidney lining and the tubules around the kidneys that are being looked at there. So it’s a great way of looking at mitochondrial DNA in the body without doing a biopsy, if you can have a lab that does it. But these things are very common, and it really depends on that individual patient. It’s more of a detection that is showing that there is this mitochondrial variant in the body, and it helps with the diagnosis.
Q: Are there any emerging therapies that any of you are excited about or that you think will be the next big thing?
A: Bruce Cohen, MD: I’ll start by saying the “Pretzel Therapeutics product (PZL-A) for Pol G disease has me excited, based on the animal model work. I think that’s a terrific concept and hopefully we’ll get to human clinical trials for mitochondrial disease soon. Right now it’s in phase 1 trials looking for maximum tolerated dose and toxicity, and apparently that trial is recruiting well and going well. And that’s in healthy volunteers. We’re very excited about the drugs that have been approved. There’s a couple drugs in the FDA right now that have a chance of getting approval based on what we’ve seen in the last couple months. So there may be a couple more. I don’t have any inside information. We’re looking forward to seeing if those drugs get approved, but once we have approval of one drug from the FDA on mitochondrial disease it sparks investment interest, and other companies that are trying to get their drugs funded for trial. These clinical trials cost tens of millions of dollars, if not more, to do even a small clinical trial, and this money generally comes from philanthropy and investment firms. And so it’s our hope it’s going to spark investment in mitochondrial disease therapies.
A: Greg Enns, MD: I agree completely, Bruce, you know, this is an area that has been lacking FDA approvals, and now we’re getting some and it’s the tip of the iceberg because investment and success brings more investment and more success. We’re all, of course, very interested in the more broad mitochondrial patient as well, although these approvals have been for specific indications, for specific types of mitochondrial disease. I think there is going to be a time when there are going to be a number of medications that are going to be available for those who have not the specific disorders that have had medications approved so far. So it’s exciting times, I think this is all good news. When approvals come, all ships rise. I just think that this is a remarkable time. I really want to highlight that, because. In the old days, so to speak, in the old days being just a few years ago, the focus was still really trying to fill a bucket with antioxidants. Or how much vitamin can we get in, and how can we do this? And it was sort of a nonspecific approach where you’re just giving a bunch of antioxidants or some cofactors. And there’s every reason to give certain cofactors, but I think the filling a bucket approach and trying to hope that there’s going to have some effect is being replaced by biochemistry and by understanding the imbalance present in mitochondrial disease patients based upon some very fundamental biochemical principles. So the medications that are coming out are really focused on doing things like changing the redox balance, looking at NAD, or Thioredoxin TRX, other components of the mitochondrial pathways that are involved in energy production. So you can go down the line from Oblivia to Senko to Contoh Soal Biotherapeutics is working on DCA for pyruvate dehydrogenase complex deficiency, and there are others of course but all of these compounds have very good potential and are fascinating to see from a biochemical standpoint – a focus on basic biology, basic biochemistry, instead of just trying something because we think it might kind of make sense.
A: Jaya Ganesh, MD: I don’t want to steal Eva Morava’s success story, but she just told us that while she was at Mayo, one of her Kearns-Sayre syndrome patients had taken Sildenafil incidentally and found a huge improvement in his visual function. He was able to see and his eye muscles were working better. He was not stumbling, and so she put him on a trial of daily Sildenafil and after 1 patient, she had 3 patients, and they’ve published this very recently, and that seems to be a game changer for some of the patients with ophthalmoplegia myopathy particularly. So as Dr. Enns was saying, understanding the biochemical imbalances and some other way to help seems to also do the trick. And the other thing I’ve got some interest now is in the immunology of some of these mitochondrial disorders. There is a lot of literature, at least that’s emerging, that’s saying that some of these pathogenic mutant mitochondrial DNA escapes and triggers a whole inflammatory cascade. And there was a very nice paper that was presented a couple of years ago at SSIEM. I’m waiting to see it published. And that might actually change the way we manage patients with Kearns Sayre, nephropathy, or some of these targeted organ system mediated damage. So I’m really keeping my eyes open for those updates. And then the Minovia, the mitochondrial replacement (augmentation), and also platelet-mediated – mitochondrial therapy that was presented at one of these research meetings. So I’m looking forward for something unique like that.
Q: How did you feel when you learned of the approvals?
A: Greg Enns, MD: Of which one? Because let me say the approval of Kygevvi absolutely delighted me. The approval for Forzinity I’m a little bit confused and happy. I’m delighted to see it approved, but a little confused that it was only approved for those who are over 30 kilograms because we’ve had some very good success in younger patients with significant heart symptoms, so I’m hoping that the future will hold for that medicine that it’ll be approved for those of all ages.
A: Bruce Cohen, MD: I was in a car as a passenger opening up the email when Elamipretide was approved for Barth syndrome. And I think my claim to fame is, well, first of all, I’ve never treated a patient with Barth syndrome with Elamipretide but I was the first physician in the world to treat a mitochondrial patient on a clinical trial with Elamipretide. And so it just brought, both joy to my heart and sadness that the indication was so narrow, but I was absolutely thrilled. And my family had to listen to the story.
A: Jaya Ganesh, MD: So, I can share my perspective. I was a co-investigator with Dr. Elsharkawi. We treated a baby and newborn a few weeks old with Elamipretide before the drug got approved, and I never thought I would be so disappointed when a drug did not get approved the first time around, and so when it did finally get approved, I was like, finally! So I think that, for me personally, I’m not sure if I will reach out to every mitochondrial patient and put them on some of the newer drugs. I’d probably use it carefully for the indications, particularly Elamipretide. I think the other drug, I feel much more confident. And then I would not hesitate to use it off-label. If, you know, the safety and the efficacy has been established for the indications that they’ve already been approved for. So that’s how I feel about it. And I also feel that this is probably not going to be a financial burden on families where at least these are approved drugs and they can be prescribed rather than bought off Amazon or a Pharmacy.
A: Matt Snyder, MD: Oh, I was extremely excited. Again, it’s narrow scope at first, but like the other folks have said, it’s just the tip of the iceberg of what the next 12 months and the future years ahead are going to look like, and for somebody who’s really just entering this field, I think the future is so bright for my patients for the next couple of decades. I think it’s just the beginning of a new era for our patients.