Motor Neurone Disease with Vanita Dahia

The diagnosis of Motor Neurone Disease (MND) is a crushing one, with the medical treatment still being one of support instead of improvement in prognosis and only a few potential treatments on the horizon. Yet there may be some hope in easing symptoms and improving quality of life (QoL) for those afflicted with this devastating disease.

In today's podcast, Vanita Dahia, pharmacist and expert in amino acid nutrition, takes us through the antioxidants, nutritional, herbal and amino acid options which can have a positive effect on the lives of those affected by MND.

Covered in this episode

[00:48] Welcoming back Vanita Dahia
[01:35] What is motor neurone disease (MND)?
[05:13] What causes MND?
[13:41] Signs and symptoms of MND?
[18:08] What role does genetics play in MND?
[21:16] The utility of amino acids
[31:15] Practitioner amino acid education
[33:46] Drug therapies for MND
[39:18] Nutritional and Herbal Medicines for MND

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Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook. Joining us on the line again today, after a long sabbatical, is Vanita Dahia. 

She's an integrative medicine clinical consultant pharmacist, naturopath, and clinical nutritionist, with over three decades of experience in compounding pharmacy, functional pathology, herbal, ayurvedic, and integrative medicine. Vanita is board certified in anti-aging and regenerative medicine with the American Academy of Anti Aging Medicine, and a member of the Professional Compounding Centers of America and Australia. Vanita's an international speaker, and author of "Alchemy of the Mind." 

Welcome back to FX Medicine, Vanita. How are you?

Vanita: Thank you, Andrew. Good to hear from you again.

Andrew: Now, today we're going to be discussing a rather devastating disease, motor neuron disease. And talking about, hopefully, some of the nutritional support that we can give these patients. But I think first, can you take us through a brief description of MND and the different types, and also some of the proposed causes?

Vanita: Sure. Look, MND has gained a lot of repute lately as a result of the passing of Stephen Hawking. 

Andrew: Yeah. 

Vanita: And he was an amazing physicist, and it just shows that MND did not affect his brain. So, what in actual effect MND is, it's a baffling disease. It's multifactorial, it's genetic, it has a lot of environmental causes as well. And it's really a progressive degeneration of the corticospinal tract as well as the anterior horn through the spinal column, and it affects the bulbar motor nuclei. 

So these motor neurons are the ones that are basically affected. We've got two sorts of neurons. The motor neurons, these are the efferent ones, they take information from the central nervous system to the periphery. And then there's the sensory neurons, and these are what we call the afferent neurons, they actually take information from the periphery into the central nervous system.

So what'll actually happen, I guess, in MND, is the cells in the center and the peripheral neurons just start dying. And the lysosome inside these cells, they give up the enzymes, they just start to die, Then you get the cellular apoptosis, in other words, the cells start to commit suicide, in a way. 

So, you know, there's quite a few...you asked about the various types of MND, and lately, there seems to be a lot...as I was researching on this topic, and realised that there's a lot of versions of MND. Where it can affect either the upper or the lower motor neurons. So the upper motor neurons, they actually originate at the frontal lobe, they go to the brain stem and the spinal cord. Whereas the lower motor neurons, they have their cell bodies in the spinal cord, so they go to the peripheral neurons. 

So this is why you will see somebody like Stephen Hawking, he had some control but he didn't lose his sensory control. In other words, he could hear, he could have all voluntary muscles working.

Andrew: He could have sensed, though, correct? There was no problem with sensation in the limbs that were affected?

Vanita: So, he could actually have...there was this actually numbing... What happens with MND is an inability in the periphery...it could affect one foot, then it affects the next foot before it hits the next organ.

Andrew: Right. 

Vanita: Or it affects one arm, to the next arm. But, they can control sexual organs, for example, they can control sphincter muscle control, initially. Later, down the line, it starts to disintegrate. 

Andrew: Right. 

Vanita: Because it's a progressive neurological disorder, so it destroys motor neurons, and they're the cells that control the voluntary muscle. So then they lose their ability to speak, and they lose their ability to walk, or breathe, and swallowing. Swallowing's a very big one. Because what actually happens, they start to swallow their saliva and their food, and it enters into the trachea, leading to a major respiratory distresses. And that's probably where a lot of the degradation happens in MND.

Andrew: So, causation. Because I thought it was purely genetic, but there are some other causes?

Vanita: Yes, yes. Look, about 10% of all MND is inherited, so there's a genetic disposition there. Autosomal dominant, essentially 90% of it is not genetic. 

So there's two streams of research that is being done in MND and its associated conditions. Just in regard to the associated conditions, one that we're probably very familiar with is ALS, amyotrophic lateral sclerosis. And you've probably heard of that, it's also known as Lou Gehrig's disease. Lou Gehrig was one of the...I guess the first person that was actually diagnosed with ALS. And so it affects...all these various conditions affect different parts of the motor neurons. So, I guess I should answer your first question first, which was the types of motor neuron disease because that will give us an indication of what can possibly cause that. 

So, the types of motor neuron disease are...one's that really are...ALS affects both upper and motor neuron disease. And then you get the other versions, like PLS, which is primary lateral sclerosis, and that only affects the upper motor neurons. And then there's another condition, which is called progressive muscular atrophy, and that affects the lower motor neurons. So, there's various versions of it, and there are some that only affect children. Like FMA is a form of neurological defect that prevents babies from...it affects babies predominantly, affects children from birth, because they're unable to think, and they often die before the age of two.

And then there's now...when you're asking about causes, there's a couple of areas of causes. There's a condition called neurolathyrism, which is a permanent paralytic condition. And it tends to be occurring in the famine-affected areas. And it's caused by this unusual amino acid called ODAP, O-D-A-P, which stands for oxalyldiaminopropionic acid. That's one, so if we look at the underlying, I guess, fingers to point, if we look at the deadly dance of nerve destruction, where is that biological spark coming from? Some of the sparks are coming from the underlying cause of perhaps exposure. So, exposure to blue-green algae.

Andrew: Wow. 

Vanita: This has been studied quite extensively by Rachael Dunlop at the University of Sydney.

Andrew: Yeah. 

Vanita: And what they've found were these blue-green algae, there're huge blooms that stretch right across the Murray, between Albury and west of Swan Hill in Victoria, in Australia, but also up north, they've found it in New South Wales, up in Murray, and Murrumbidgee River, along there. 

They've found that these blue-green algae, what they do is they contaminate food. They move into the food chain. And they do this by mimicking an amino acid. They mimic L-serine, which is an amino acid that prevents them, the amino acid, from actually folding and functioning properly. So that then leads to that toxicity.

So they found that this particular toxin is called BMAA, which beta-methylamino-L-alanine, another amino acid. This is a toxin that they found not only as a result of exposure to these blue-green algae, and they bio-concentrating in these cells. But also they found that this particular toxin was also found in unwashed cycad seeds. 

Cycad is actually a seed found in Guam and Papa New Guinea, and they actually found these seeds in Japan as well. And what they do, these ethnic groups, including Aboriginals here in Australia, they found that the Chamorro tribes use these seeds, these cycad palm, it's a palm seed, and they use to make tortillas and dumplings out of it. But they were very smart, the Aborigines knew that they needed to wash the flower of all the poison before they could use that. 

Now, those are didn't wash that were accumulating BMAA, which is your beta-methylamino-L-alanine, and they were exorbitantly high in patients with MND. So it just is a bio-concentration of that underlying toxicity. And you know what? They also found that in bats, these Chamorro tribes, they ate bats, and they found in this area of Guam and Papua New Guinea, these bats were consuming or had high levels of BMAA. And they found that that was contributing towards the toxicity as well. So it's quite interesting, isn't it?

Andrew: Yeah. Can I just ask you, with regards to bats, there's this worldwide issue of bats being knocked out by fungus. I'm wondering if that might have any play to a part in the increasing incidence of this amino acid found in the bats? And I'm wondering therefore, if it might be something along the lines of an aflatoxin that we'd see nuts from fungal production?

Vanita: As a result of... I guess I can't answer your question effectively, because I don't know. 

However, as a result of these blue-green algae and these various blooms, as well as the fact that the cycad seeds are found in tropical, dense forest's palm trees, there is a high propensity of accumulation of aquatoxins, aflatoxins leading to conditions that we now know and are well recognised as neurodegenerative conditions. 

Andrew: Ahh, okay. 

Vanita: And that is your mould biotoxins, your Lyme disease, and they're all presenting with really significant autoimmune pictures, such as we call them chronic fatigue syndrome, we call them Lyme Borreliosis, so there may be an opportunity for us to investigate that further.

Andrew: This is the sort of thing that interests me, is that we, as humans, we like to target something and say that was the cause. But then, if you delve further and you look back and back and back, there might be some other factor causing that thing to happen in that vector, organism, whatever. And we attribute the vector, whereas the real culprit was something far more distant.

Vanita: That's true. Yep, yep.

Andrew: That blue-green algae, though, that's really interesting.

Vanita: It is, and it's been very well researched lately, as a result of, as you probably well know, in Australia we have the Ice Bucket Challenge, you know? And so there's a fair amount of research which is, fortunately, being funded and operated right here in Australia. Particularly in the genetics area as well. And I know that it only affects 10% of MND, but there's some really interesting genes that have been identified and associated. So there's a race to find the genetic construct associated with MND.

Andrew: Wow. So, it's such an important area of a devastating disease. What about the symptoms, though? Is it always insidious? Like, I remember in the movie of Stephen Hawking...

Vanita: "Theory of Everything."

Andrew: That's it, "The Theory of Everything." I remember, you know, it started off with a little bit of clumsiness, and that's often what people present as. They tend to knock, you know, a hip on the desk all the time, and it's like, oh, that's strange. And then suddenly there seems to be this quite a significant drop in functioning of the muscles. 

Vanita: Yes. 

Andrew: Does it always start with just this weird insidiousness, and then bang, there's this steep progression in the disease?

Vanita: That's correct. You will find that there's usually a slow onset. And what it does, it affects...the signals to the cortex just don't work, it's broken. So the nerves get attacked. So the first thing you will see is some form of palsy. So it's usually a bulbar palsy. Where you see some level of paralysis. And it usually might affect just a foot, initially. And then it'll affect the next foot, and then it'll start affecting speech. People will find that they aren't able to speak effectively or articulate their words effectively. And they might experience, you know, muscle tremor, and then they start to develop...then it starts to progressive, as limbs become wasteful, in other words, muscles become atrophied. And, you know, there's just no nerve supply to the muscles. And so...but, the important thing is that the sensory neurons are okay. 

Now, with the Bell's Palsy, or the bulbar palsy, is actually, it's progressive, because it affects the bulbar nuclei. These are the cell bodies in the brain stem. And they cause these...it's a cranial nerve process which causes weakening of facial muscles, causes swallowing issues, then it affects the pharynx and the epiglottis. And then the first sort of facial-type symptoms people will experience is dysphasia, which is lack of swallowing. And then they develop dysaphia, which is inability to articulate words, or that speech gets affected. And where it really hits the bad spot is when you see this nasal regurgitation. Now, you will find aphagia and other conditions like stroke, you might even find it in Alzheimer's disease. So there's a general threat in the genetics in relation to some of these symptoms.

But the cognition features, these guys know exactly what's happening. So they've got no...there's no presenting...everything's preserved in the relation to their sensory and cognition features. So they're aware of things, you know? And their eye muscles are also well preserved, as you would have seen with Stephen Hawking.

Andrew: Yeah. What about things like central control of temperature, vs. peripheral control? Like, I would imagine if you can't move your legs, then you haven't got the veins pumping up blood from the periphery. So, therefore, you might get pooling of fluid in the ankles, like dependent edema. Which, of course, might affect temperature in the peripheries. Is there any central dysregulation of things like temperature? That would be more of a hypothalamic type thing, wouldn't it?

Vanita: It probably would be, and this is not a typical presentation in MND. It's motor neurons that are affected. 

Andrew: Yeah, yeah. 

Vanita: So, what you will find more than fluid retention, or...those are secondary events. Because secondary events is associated with inability to address those primary defects. So you might find rather than fluid retention, you might find pressure sores as a result of inability. Or respiratory infections, rather than temperature control. There may be a thyroidal imbalance, or adrenal imbalance later down the line. But the primary construct of MND is associated with that motor neuron dysfunction.

Andrew: Although it's only 10%, I think it's a static, if you like, thing that researchers can focus on for causality and hopefully some treatment, that's the genetics. Can we delve into a little bit more of the genetics? What sort of genes were identified, and how are they, sort of, proposed to be an effect, if you like, of the condition?

Vanita: Well, as I said, there seems to be a bit of a race going on as a result of further studies on genetics. We're using genetics to identify our ancestral lines, and now geneticists are on the bandwagon identifying specific gene mutations associated with MND. Some of them might be hereditary, others might be somatic or acquired. 

And you will find that the ones that are currently studied, genes like NEK1, and this is involved in motor neurons helping keeping the shape of the motor neurons, and keeping the transport systems open. Another one, another gene that is studied quite extensively right here in Australia is C21ORF2, and also C9ORF72 gene. These genes are really abundant in nerve cells and neurons, and they're involved in the outer layers of the brain, like the cerebral cortex, and they involve your control movements, like your motor neurons. So we're finding that that gene is also being identified. And one that we're quite familiar with is superoxide dismutase, SOD1.

Andrew: Oh, yeah?

Vanita: Yeah, in 1993 that gene was identified, and we found that about 20% of familial... Remember, only 10% of MND is familial. So 20% of these genetically predisposed MND patients have had SOD gene mutations found. And they found in… right now, at the moment, they've also found that they'd account for about 65% of all MND. This is the latest study, in terms of genetical or familial MND. 

Another gene that is... See, all these genes tend to affect how proteins actually build up, and these toxins migrate to the cells. Another one that is of...I guess being studied at the moment is TBD-43 gene. It's another one that is being associated with MND. And, your heat shock protein 27, HSP 27. These are basically transactive protein responses, and they express really early in development, before birth, and they're involved in the nervous system and these organ development dysfunctions. 

So, these are some of the genes that are now currently being talked about and studied and reported in the literature, at the moment.

Andrew: When we're talking about these genes, can you take us through what's happening with the pathophysiology at the cellular level? Like, are we seeing a damage, if you like, maybe parallel to Alzheimer's? Like, you know, the neurofibrillary tangles, the beta-amyloid plaques, are we seeing these genes cause a similar type of pathophysiological process?

Vanita: The pathophysiology of MND is not being defined. But there are a few theories out there. And a lot of them are studied, and quite extensively studied. And a lot of them are associated with the toxicity of your beta-methylamino-L-alanine. Whether it is derived from your ingestion of cycad seeds, or whether it is as a result of exposure to blue-green algae, these neurotoxic elements, they basically accumulate, and they're miss-incorporated, as a result of poorly functioning recycling and refolding machinery of the proteins. And so what they do is they don't fold correctly, and they build up as, like, junk inside the cell over time. And that junk eventually chokes up that cell, and it sends that cell into a programmed death, or suicide, you know?

Andrew: Right. 

Vanita: And so our focus, therefore, and a lot of the study has been along the lines of two mechanisms. We have the only approved drug called Rilutek, or Riluzole. And there are two mechanisms by which it works. One is it is an NMDA inhibitor, and the other is that it is a glutamate antagonist. 

So the theories that are postulated as a result of seeing these high levels of BMAA can be associated with what is causing that underlying issue? So having researched a lot about amino acids, and as you probably well know, I love my amino acids...

Andrew: Yeah. Yes.

Vanita: I've actually investigated the effect of where BMAA, why does it become neurotoxic? Now, we know that it actually occupies the serine receptors, allowing for glycine and serine to be depleted in the bloodstream. But...and the reason being is that they're occupying those receptors. So they're mimicking, BMAA is mimicking the effect of serine. 

So currently, in various blogs, you can often see patients are taking serine. Now, as a result of researching a little bit about this, I use my amino acids at the rate of anywhere between one and three grams per day. But serine, in this instance, is being given up to 30 grams per day.

Andrew: Wow. 

Vanita: And we have noticed some changes. Again, there's still a lot of study to be done in the area of amino acids, but it's really working along the lines of two major mechanisms that we know of. And obviously, there are many more mechanisms at hand, which we still need to understand.

Andrew: So, just with regards to serine, if you're using 10 times the amount that would normally be used. Is there potential for... I don't want to make a wild claim of cure, right, that's out of the bounds of reality. But an abrogation of symptoms, so that you get a lesser decline?

Vanita: There are a number of...there's so many various theories and postulations out there, just getting an understanding of why these medicines are working, and under which pathways they're working, opens up the opportunity for integrative practitioners to understand the mechanism, and then look at those constructs. 

Serine is a amino acid, which is your intermediary precursor to glycine, which is needed for manufacture of GABA. So we found that GABA agonists, such as Gabapentin, has also been used but has not shown any beneficial effect in MND patients. But, serine is actually a really important amino acid. It's used in the folate pathway in methylation, but it's more importantly used to manufacture nerve cell sheaths. It's used in production of immunoglobulins and antibodies. It's used in the synthesis of glycine, of choline, of your fatty acids, and your sheaths around these nerve fibers. And it's also involved in transamination from glutamate, so that glutamate toxicities leading...is associated with serine, so there's a blockage in the nerve pathway, somewhere along the line. 

Andrew: Yeah.

Vanita: These proteins are not being folded effectively, and so your BMAA is becoming toxic as a result of the lack of the mechanisms of conversion, and synthesis, and manufacture, and metabolism of serine, glycine and there's a number of other amino acids as well.

Andrew: You mentioned serine and you mentioned choline, which of course are components of two of the lecithins. Phosphatidylserine, phosphatidylcholine, and you're talking about nerve sheaths. Phosphatidylserine's shown facility in helping to protect against certain damages. Do you ever use phosphatidylserine, or PS, or do you use the amino acids and some of the substrates that might be used in helping to make the sheaths?

Vanita: All right, so there's a number of opportunities here. You can use something like fendiline, as example.

Andrew: Yeah. 

Vanita: Which is a signalling molecule, which really is supporting myelin sheath production. But from an amino acid perspective, your cholines are absolutely essential. They are manufactured through the SAMe pathway in methylation. They are needed for your cell membrane, phospholipid membrane function. They're also needed to maintain the fluidity and the surface tension of every cell. 

But most importantly, they are needed as neuromodulators. That is the ocean under which your neurotransmitters fire. If you don't have your choline derivatives, they are not neurotransmitters, they are modulators.

Andrew: Right. 

Vanita: And they are actually the ocean. So if you have your neurotransmitters firing across a dry dock, you've got no neurotransmission induction pathways happening, and the reason is that you don't have those choline derivatives. 

Now, choline could be choline, inositol, some of L-theanines, these are related. Phosphatidylcholine, phosphatidylinositol. These are very, very important neuromodulators that would play an adjunctive role. Perhaps not a primary role, but an adjunctive role.

Andrew: Yeah. 

Vanita: And like herbs, amino acids do not work individually. They work synergistically with each other, because one interconverts to the other. So typically, I would actually identify amino acid status.

Andrew: Yep. 

Vanita: And then fit in the varied amino acids. Some other work has already been done by Deanna Protocol. It's a metabolic therapy predominantly aiming at providing the fuel in the citric acid cycle intermediates, and specifically...and I use this as well...is the AAKG. Which is arginine-alpha-ketoglutarate, together with alpha-ketoglutarate, that stimulates that succinyl-CoA a pathway in the citric acid cycle. Together with branched-chain amino acids, so that's leucine, isoleucine, and valine, very important. Together with methionine, creatine, creatine has been shown to be very, very effective in building up your muscle sheaths. Choline and its derivatives, arginine, and there's a whole bunch of other amino acids. 

So I use a synergistic blend of these amino acids, and these amino acids are never working on their own. They're working with specific B-group vitamins and magnesium to stimulate, it's co-factors are needed to stimulate its conversion, utilisation, synthesis and metabolism. So, I find that the amino acid therapy is very, very useful, in line with other antioxidants.

Andrew: I gotta say, as soon as you said the use of the drugs as an NMDA inhibitor, I was thinking magnesium for anti-excitation action, you know, and reducing the calcium flux inside the cell.

Vanita: Absolutely.

Andrew: Dose of magnesium? Do you ever have to go massive dose, like you're using massive doses of the amino acids, the serine?

Vanita: Look, I have never used a high level of serine, I tend to use a synergistic blend of it. But having done the research lately, I would probably be increasing the level of serine in the amino acid blend for these particular MND titrations.

Andrew: Yep. Obviously, people have got to learn about these blends, and indeed, what to use. Have you developed anything to teach other people about this?

Vanita: Look, amino acids have been an area that I'm really passionate about. And so yes, I've developed a master class on amino acids. Right from the boring stuff about each amino acid and the materia medica about...and more importantly, therapeutic value of these amino acids. How they interplay with each other in the gastrointestinal system, or in specific disease states, neurological systems, etc. 

And the cherry on the cake is actually how to compound amino acids using an algorithm that I have used in my compounding pharmacy days many, many years ago, and is still used today by some of the compounders that I've passed the information on to. So yeah, so that's an amino acid master class.

Andrew: Yep. 

Vanita: It's called "The Alchemy of Amino Acids," in line with my book, called "Alchemy of the Mind." 

Andrew: Yeah.

Vanita: So, "Alchemy of the Mind," incidentally, is a book that I published last year about neural chemistries. And one of the chapters is really how neural chemistry, or the chemistries of neurotransmitters affect every organ system. 

Andrew: Yes. 

Vanita: Whether it be, you know, the adrenals, or the thyroid, or the gut, there's a huge plethora of publicity about the gut-brain axis. So, you know, it's connecting all these dots, and how the brain affects libido, stress. And you know, also the toxicants, we're so exposed to toxicants.  And as we well know, you know, MND can play a role in...or has a underlying causative effect of perhaps some level of toxicity.

Andrew: Yeah. So, I've got to ask so that you can give the details for our listeners, where and when is this course being taught? Do you do it regularly, or have you only done it once or twice?

Vanita: This course will be available online, and so yes, definitely contact me at vanitadahia.com, or just look me up on the website and it will be available.

Andrew: We'll put that up on the FX Medicine website for our listeners, definitely.

Vanita: That will be lovely. Yes, thank you.

Andrew: Yeah. What about drug-nutrient interactions? You're dealing with, you know, drugs that are trying their best to decrease damage to the motor neurons, you'd have to be acutely aware of interactions. Any major things to be mindful of here?

Vanita: I think more, rather than interactions, is how do we manage this patient? What are the current drug therapies available? And then look at the patient's effect. For example, you know, the swallowing reflex, the cramps, should we use baclofen, should we use various anti-infective agents? So there's a number of trials that are out there. Shall I tell you about some of the trials on some of the drugs that are being used?

Andrew: Please. Yes, yes, yes. Please do.

Vanita: Okay. So, there are some trials, and obviously with every drug comes a materia medica. So you have a look at the MSDS file, and definitely look at the side effects and investigate their interaction. 

But most importantly, it's quality of life for this MND patient. Obviously, these patients are immobile, and so these drugs are going to play a role. So they're going to have the gastric reflux, so you might need to use a PPI. But some of the major drugs that are currently being investigated right now and undergoing phase I/phase II trials, some of them are...Tamoxifen, which we know is used for breast cancer. Talampanel, these are currently in phase II trials. Antibiotics which we are using for severe bacterial infections, like minocycline and ceftriaxone are in phase II trials as well. Thalidomide, the horrible thalidomide, is also being trialed at the moment.

Now, there's some interesting stuff going on. We are now trialling...the next frontier in the treatment of MND at the moment is...Carlo, Carlo Rinaldi, he's published in Natural Reviews of Neurology, and he's talked about the next frontier in treatment of neurological disorders. And that is your ASOs, antisense oligonucleotides. 

Now, we use these nucleotides, they basically inhibit viral replication. And the first generation was used predominantly for cytomegalovirus. But now they're finding that they can bind to non-coding RNAs and toxic RNAs. So there're two drugs currently on the market, put out by Biogen under the name of Spinraza, and that's called eteplirsen and nusinersen. These are two drugs that are currently out on the market, and they've just gained FDA approval.

Another mechanism which we should be looking into is the issue of copper-ATSM. 

Andrew: Right. 

Vanita: In late 2016, there was a collaboration of various professors at the University of Melbourne, Dr. Anthony White, Professor Paul Donnelly, they actually looked at this particular mechanism of copper and they are virtually repurposing some of the HIV drugs. One of which is called Triumeq, T-R-I-U-M-E-Q. And it's working along the copper pathways. So, don't understand the mechanism yet, but it is involved in some of the studies. 

Andrew: Wow. 

Vanita: Another one that is possibly worth making mention of is some of the Cytokinetics, they're in phase II clinical studies. This has just been presented very recently, in 2018, at the Annual Cure SMA conference. Dr. John Day has been involved in the release or study of Reldesemtiv. It's currently a subject of three phase II clinical trials at the moment.

Andrew: Yep. 

Vanita: It is a product released by Astellas Pharma, that's one that's being studied at the moment. 

Another one that's being studied is squalamine. It's an anti-cancer and antiviral drug. And they've found that this particular drug affects the aggregation of alpha-synuclein. Now, the synuclein accumulates when iron accumulates in the production of L-dopa. So when L-dopa's not formed sufficiently, then iron starts to accumulate, and that increases the aggregation of L-synuclein. And this is where...

Andrew: Is that, like, parallel to Parkinson's?

Vanita: It's parallel to Parkinson's. A lot of their studies are now worked along the lines of Alzheimer's, Parkinson's, and these neurological diseases. 

Andrew: Wow, wow.

Vanita: So, there's quite a few, you know, studies. One in Japan is also being done by Mitsubishi Pharma on Edaravone, that's another drug. 

And then, look, we have, like, that we're using right now, like leucine, valproic acid, we're using some of your ciliary neurotropic growth factors, phenylbutyrate, gabapentin, all with varying degrees of efficacy.

Andrew: Yeah. And what about natural agents? Any research, or is there anything else that's useful, apart from the amino acids? You know, like you mentioned the B-vitamins, and I'm wondering about herbs, I'm wondering about if there might be anything that's useful?

Vanita: Yes. So, some of the natural items that are used currently and with great effect, the whole focus on natural ingredients is to support the motor neurons and provide the antioxidation, intercellular antioxidation, also supporting the glutathione production as well. 

So, alpha-lipoic acid does that, your B12 methylating cofactors, B12 and folate. They are involved in Bell's Palsy. Coenzyme Q10 is a very powerful antioxidant.

Andrew: Of course.

Vanita: It's a major coupling agent within your electron transfer chain, and it helps with energy production. Magnesium, obviously. Magnesium's a very powerful NMDA... Oh, sorry, it helps lower your glutamate toxicity. 

Andrew: Yep, yep. 

Vanita: And as we're looking at glutamate toxicity, there are other things such as theanine, taurine, green tea Baical skullcap, curcumin, ashwagandha or Withania.

Andrew: Yeah.

Vanita: Vitamin B6, magnesium. Some of your brain-smart brain foods such as Vinpocetin. These are used as natural agents to assist with glutamate toxicity.

And then the other mechanism we spoke about as well is your NMDA receptors. They are antagonised or inhibited by, as you said earlier on, magnesium, yes. But hormones, like progesterone, as well is an NMDA inhibitor. We use [inaudible 00:41:08] taurine, taurine activates your GABA receptor, so it's a great NMDA antagonist. Amantadine is a drug that is used for Parkinson's and Alzheimer's, that's another an NMDA inhibitor. 

Amino acids like agmatine, which is a metabolite of arginine is also an NMDA inhibitor. You can use drugs such as a dextromethorphan, and that's used in your cough syrup.

Andrew: Yeah.

Vanita: Orphenadrine, which is basically a muscle relaxant, methadone, ketamine, memantine, these are your drugs, opioid drugs. There's been a couple of studies on the use of nitrous oxide as well, so laughing gas as an NMDA inhibitor.

Andrew: Wowee.

Vanita: But as far as herbs are concerned, one very important amino acid is N-acetylcysteine as well. 

Andrew: Yeah.

Vanita: You mentioned herbs. So, some of the herbs that are currently used, are… the focus in the case of herbs is really neuroprotection, anti-inflammatories. So some of the herbs that are used in neuroprotection are lion's mane, Withania, which is a nervine adaptogen. But then there are other neuroprotective herbs as well, and I'm sorry I can't remember its generic name either. Like bacopa, Baical skullcap, Gotu Kola, these are our...holy basil. These are really great other neuroprotective agents. There's one that is worth making mention of, and this is a Chinese study, using intravenous crude Astragalus root.

Andrew: Wow.

Vanita: So, don't know enough about it, but I do know that it is used in MND as qi invigorating herbs. And they've done a report of 31 cases, so that's quite interesting.

Andrew: Gosh. And quite large for MND, because it's not going to get a lot of...you're not going to be looking at huge cohorts of patients, anyway, thankfully.

Vanita: No, you can't look at very many, because of the percentage of patients. But there is room for further study in the area of herbs. With MND patients, they have inflammation. So you've got to reduce that with herbs such as Bupleurum, turmeric, Baikal skullcap, cat's claw. Cat's claw and Baical skullcap are probably the two major herbs that you would use. 

Andrew: That’s interesting. Yeah.

Vanita: Cordyceps and Reishii as well. Astragalus, hemidesmus, which is obviously an immunosuppressant, they're also being used.

Andrew: There's obviously so much to delve into here, and I think responsibly you'd have to look at this in a formalised setting. I think I must urge our listeners to undertake your training program, with regards to compounding of amino acids and also other nutrients as well, to combat something as serious and as devastating as motor neuron disease. 

Vanita, I can't thank you enough for taking us through this. You have obviously delved into this a massive amount. And thank you so much for taking us through your expertise today on FX Medicine.

Vanita: Thank you so much.

Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook

 

Additional Resources

Vanita Dahia

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Other podcasts with Vanita include

• The Neurobiology of Libido with Vanita Dahia

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