Artificial sweeteners and cancer; stool transplants; new epilepsy treatment: Upstate Medical University's HealthLink on Air for Sunday, Oct. 22, 2023

Host Amber Smith: Coming up next on Upstate's "HealthLink on Air," we explore research into how commonly used sweeteners can cause liver cancer.

Andras Perl, MD, PhD: ... Sugars in general are not healthy, and they support -- at least in the liver -- potentially abnormal growth. ...

Host Amber Smith: We look at why stool transplants are better than antibiotics in treating a dangerous diarrheal illness.

Aamer Imdad, MBBS: ... The C. diff infection happens when the balance of good bacteria versus bad bacteria tilts towards the bad bacteria. ...

Host Amber Smith: And we learn about the potential new era of treatment for severe forms of epilepsy.

Robert Beach, MD, PhD: ... There's the ability to take stem cells, differentiate them into specific cell types, and then to save them in very specific parameters so that they're always the same in every sample. ...

Host Amber Smith: All that, and a visit from The Healing Muse, coming up after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine with the experts from Central New York's only academic medical center. I'm your host, Amber Smith.

This week's show features three Upstate clinical researchers. We'll learn how stool transplants work better than antibiotics for treating the diarrheal illness known as C. diff. Then, the chief of epilepsy tells about the success of regenerative cell therapy implants for uncontrolled seizures. But first, commonly used artificial sweeteners can cause liver cancer.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

Commonly used sweeteners can cause cancer of the liver, according to research conducted recently at Upstate. I'm talking with the lead author of that study, Dr. Andras Perl. He's a SUNY (State University of New York) Distinguished Professor and also the division chief of rheumatology at Upstate.

Welcome to "HealthLink on Air," Dr. Perl.

Andras Perl, MD, PhD: Thank you, Amber. It's nice to be with you.

Host Amber Smith: You and your colleagues published your research in the journal Nature Metabolism, and I wonder what the response has been like from other scientists. Is this the first paper to show that sugar substitutes can cause liver cancer?

Andras Perl, MD, PhD: This is the first paper, and we were, ourselves, surprised how effectively we could block the development of cancer by eliminating the sugar from the blood and other tissues of these mice. But this also has relevance for human subjects.

Host Amber Smith: Have scientists suspected this connection for a while, and have they been looking for proof of this, or is this something brand new?

Andras Perl, MD, PhD: This is brand new. I have been suspecting this for a long time, and we uncovered many, many years ago that these sugar alcohols accumulate in mice and human subjects that lack this enzyme. And we uncovered that this human subject developed liver disease.

First, we found it in mice, that 50% of mice that lacked the enzyme had liver cancer. And subsequently, human subjects, mainly children, were found to develop very aggressive liver tumors who had this enzyme deficiency, but nobody directly linked the accumulation of the sugar alcohols to cancer.

We also uncovered another enzyme called aldose reductase is highly overexpressed. We did know that aldose reductase generates the alcohol from the sugars that accumulate in the absence of transaldolase. So we published a paper on the subject that transaldolase-deficient mice developed liver cancer in 2009, which was 14 years ago. And in this paper we showed that sugar alcohols accumulate in these mice, and this other enzyme, aldose reductase, is also overproduced in the mice. And later on, human subjects were found that also lacked transaldolase and developed liver cancer, but they were unsure whether the accumulation of the alcohols was actually driving the cancer.

We suspected that the overactivity of another enzyme was contributing to the accumulation of the sugar alcohols. So then, to find out whether this other enzyme contributed to the development of cancer, we generated mice that lacked both enzymes, both aldose reductase and transaldolase, and those mice did not develop cancer, and they did not accumulate sugar alcohols.

So this other enzyme, aldose reductase, converts the sugars that accumulate in the absence of transaldolase. The other enzyme converts them to sugar alcohol, and that apparently is highly carcinogenic. That's what we discovered in mice, but this also applies to humans because humans who lack transaldolase also accumulate these sugar alcohols to the same degree as mice do.

Host Amber Smith: I want to ask you some more specific questions about your work, but when a finding like this comes out and is published in a prestigious journal like this, do scientists congratulate one another, or are you more competitive?

Andras Perl, MD, PhD: That's a good question. I did get a few congratulations, but not too many, but maybe others expected this to happen, or I don't know what they think. The question is actually interesting.

Host Amber Smith: Well, please tell us more about how your study was designed. What sweeteners did you focus on?

Andras Perl, MD, PhD: We did not focus on sweeteners specifically. We knew that these alcohols accumulated in these mice. And, we suspected that the generation of the alcohols was mediated by the other enzyme aldose reductase, which was over-produced.

And we thought that these, the accumulation of the sugar alcohols contribute to the disease, but we didn't know if it was contributing to the cirrhosis that prevents cancer, or it was also contributing to cancer. We only found this out when aldose reductase was inactivated, and the mice no longer made the alcohols, and they no longer developed cancer.

So that indicated to us that these alcohols actually, the sugar alcohols, induced cancer. Subsequently, we also treated cells, in vitro cancer cells, and we found that they highly over-proliferate if you treat them with sugar alcohols in vitro. So the sugar alcohols themselves induced cancer cell proliferation. We also used inhibitors of aldose reductase, not just genetically inactivated it, but treated cancer cells with drugs that can inhibit this enzyme and they inhibit the proliferation of cancer cells.

So we do know that not only genetic inactivation of the enzyme can prevent cancer, but very, very likely inhibiting the enzyme with drugs can also inhibit cancer formation.

Host Amber Smith: So these two enzymes that you keep mentioning -- the transaldolase and the aldose reductase -- do healthy people have both of these enzymes in ample supply?

Andras Perl, MD, PhD: Yes. Normal people have both of these enzymes in ample supply, and one can imagine that through the generation of sugar alcohols, aldose reductase could contribute to cancer formation.

On the other hand, transaldolase protects from cancer, so individuals who lack transaldolase develop liver cirrhosis and cancer. So this enzyme protects from liver disease.

And we also uncovered that this enzyme also protects from Tylenol-induced liver failure, which is the leading cause of acute liver failure in humans. We found in another study that people who develop liver failure due to Tylenol overdose, a great percentage of them lack transaldolase, at least, one allele of the enzyme is mutated in those individuals. So this enzyme deficiency also predisposes to Tylenol-induced liver failure, and inactivation of aldose reductase also protects from Tylenol-induced liver failure in mice. So we can presume that in human subjects who develop liver failure due to Tylenol overdose, inhibiting aldose reductase may also be helpful.

Host Amber Smith: This is Upstate's "Health link on Air," with your host Amber Smith. I'm talking with physician-scientist Dr. Andras Perl. He's a SUNY Distinguished Professor who led research recently showing how an ingredient in sweeteners can cause liver cancer.

So what do these sugar alcohols do that leads to cancer of the liver? And I know that it involves the enzyme as well.

Andras Perl, MD, PhD: So, sugar alcohols, we don't know exactly how they cause cancer, to answer your question flatly, but we have some suspicions what they might do.

Sugar alcohols create osmotic pressure in the cell. When the cells are exposed to alcohols rather than sugars, they cannot be metabolized, not as readily as sugars, and the alcohols themselves cause osmotic pressure that turn on genes that mediate cell proliferation.

So one of these genes are called "junk," or JNK. So these genes promote DNA replication and cancer proliferation. So I think the osmotic pressure that they create is what drives carcinogenesis. This is a very crude answer, and much more details need to be discovered.

Host Amber Smith: Would this only be a concern in the case of that JNK gene?

Andras Perl, MD, PhD: So this junk gene, or JNK, is involved in most cancers. So it is possible that activation of these genes, through osmotic pressure, contributes to many forms of cancer. In fact, in our paper we showed that inhibiting aldose reductase also blocks the proliferation of breast cancer cells. So this mechanism of enhanced carcinogenesis by sugar alcohols may not be limited to liver cancer.

Our model was limited to liver cancer, but this mechanism may apply to other forms of carcinogenesis.

Host Amber Smith: And the sugar alcohols we're talking about are found in sorbitol and erythritol?

Andras Perl, MD, PhD: So sorbitol and erythritol are sugar alcohols, and these accumulate in the absence of transaldolase. There is one additional alcohol that we detected highly, which is highly accumulated, called sedoheptulose, which means that it has seven carbons that make up the sugar. Carbon is coal. The main ingredient of coal is carbon. That's an atom. And the sedoheptulose has seven. The sorbitol molecule has six carbons. Erythritol has four carbons. And these carbons are actually formulated in our body by a pathway called the pentose phosphate pathway. And that's where these two enzymes are functioning in our body. The aldose reductase and the transaldolase are a part of this pathway that generates sugars that contain various numbers of carbon atoms. So the erythritol, which is used as a sweetener very commonly, or sorbitol, have four or six carbons.

Host Amber Smith: So these sweeteners, which are on the market and are in different products now, do you think the FDA (Food and Drug Administration) needs to reconsider whether these products containing these should be sold?

Andras Perl, MD, PhD: Absolutely. So the reason that they found them to be safe is that they cannot be detected in normal individuals. But they have not been measured in a tumor environment, so nobody knows to what degree they are available in tumor environment. And from our study, it's very clear that a very high level of them drives cancer.

Whether or not consuming these sugar alcohols can achieve that concentration anywhere in our human body is a matter of further discovery. It's unknown whether these concentrations that we detected in our transolodase deficient mice can occur in human beings who just consume these sweeteners. But, one can assume if somebody has a predisposition, that will be greatly enhanced by consuming these alcohols. So whoever is drinking these sugar alcohols is taking on a greater risk of cancer development.

Host Amber Smith: Well, compared with artificial sweeteners, does regular sugar, does that pose a threat to the liver the same way?

Andras Perl, MD, PhD: The quick answer is yes. It turns out that sugars, especially refined sugars like glucose, for example, support cell proliferation in a much robust and potentially toxic way than other carbohydrates or, for example, fat.

Fat can be burned much more effectively through mitochondria than sugars, which tend to preferentially go into glycolysis, which is a pathway more commonly used by cancer cells. Sugars in general are not healthy, and they support -- at least in the liver -- potentially abnormal growth.

On the other hand, we do need sugar for the brain to work. Our brain cells depend on sugar. That's the main source of energy for brain cells. So, deprivation of humans from sugar or sources of sugar is probably not something that we should aim for. But limiting sugar might be helpful in general, especially thinking about liver cancer.

Host Amber Smith: Now, your work on this particular study was done in laboratory mice, so I wonder is it going to be replicated in humans at some point?

Andras Perl, MD, PhD: Some aspects of this work has been conducted in humans. So, others have measured the sugar alcohols in patients who lack transaldolase, and they highly accumulate. They also accumulate in human subjects who develop liver cancer and lack transaldolase. So, very clearly, this is present in subjects who have liver cancer and transaldolase deficiency.

Nobody has studied the expression of aldose reductase in these individuals. However, aldose reductase is known to be overexpressed in all kinds of liver cancers, including those where transaldolase is not deficient.

So the overexpression of aldose reductase is very clearly a driver of liver cancer outside the deficiency of transaldolase. So inhibiting aldose reductase could be a very general mechanism of blocking liver cancer in general. And if we believe that that inhibits cancer, the mechanism of that involves diminished production of sugar alcohols.

So I must say that sugar alcohols drive liver cancer in general, probably outside transaldolase deficiency.

Host Amber Smith: After seeing these results, have you and your colleagues removed things from your diet that contain added sweeteners?

Andras Perl, MD, PhD: Actually, one of my technicians in the lab -- his name is Joshua Lewis, and he greatly contributed to this work because he is genotyping these mice -- told me last week that he actually tried to lose weight. He actually is relying on sugar alcohols. And he has many friends that he's chatting with on the internet, and they use sugar alcohols for achieving weight control, which may work at this potential cost. So I believe that he will be removing this from his diet.

I personally have not used sugar alcohols not at least knowingly. But I believe that people should cut this out of their diet now.

Host Amber Smith: Well, Dr. Perl, thank you so much for making time for sharing this with us.

Andras Perl, MD, PhD: Thank you so much for having me, Amber. Thank you.

Host Amber Smith: My guest has been Dr. Andras Perl. He's a SUNY Distinguished Professor and the division chief of rheumatology at Upstate. He also teaches and does research in biochemistry and molecular biology and microbiology and immunology. I'm Amber Smith for Upstate's "Health Link on Air."

Antibiotics versus stool transplants -- next, on Upstate's "HealthLink on Air."

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

An Upstate doctor did research that shows a better way of treating a life-threatening diarrheal illness, and he's here to tell us about it. Dr. Aamer Imdad is an assistant professor of pediatrics, and he specializes in nutrition and pediatric gastroenterology.

Welcome back to "HealthLink on Air," Dr. Imdad.

Aamer Imdad, MBBS: A pleasure. Thank you.

Host Amber Smith: I'd like to start by having you tell us about this diarrheal illness that can be so severe. What's it called?

Aamer Imdad, MBBS: The name of the infection is Clostridioides difficile. It used to be called Clostridium difficile. In short we call it "C. diff."

It's an infection that can cause diarrhea because of inflammation in the colon, which is the large bowel.

Host Amber Smith: Where does C. diff come from? How does somebody get it?

Aamer Imdad, MBBS: Many of us actually have C. diff in our large bowel. The C. diff infection happens when the balance of good bacteria versus bad bacteria tilts towards the bad bacteria, so it is present in the form of spores, so it can survive for a longer period of time.

And as it gets the opportunity to grow faster and produce a toxin, that can lead to the illness, which could be very severe, especially in older people.

Host Amber Smith: Is that why it can be potentially life-threatening? Is it mostly for older people or people with compromised immunity?

Aamer Imdad, MBBS: To a certain extent. So, it can happen in immunocompetent patients as well. So, what we have seen over time is that it is actually the most common gut-associated infection acquired from the hospitals, so it's more likely to happen in patients who have been admitted in the hospital for a longer period of time. We have also seen patients getting this infection in the community as well, and we have seen it in children, young adults and then adults in old age as well.

It tends to be more severe in patients in older age, but it can happen at any age beyond the childhood period.

Host Amber Smith: And how is it usually treated?

Aamer Imdad, MBBS: We can actually go back and kind of say, why does it happen in the first place? So the most common reason for having C. diff infection is use of antibiotics.

Most of the time, a patient will go on antibiotics for reasons, let's say, pneumonia or urinary tract infection, or, in children, for example, they could be treated for ear infection. And that not only kills the bacteria that was causing that infection, but it also kills the good bacteria in the gut, and that gives an opportunity for the C. diff to grow, leading to infection.

So, once somebody has diarrhea, and they get tested positive for C. diff, the initial recommendation is to treat the C. diff infection with antibiotics. And there are certain types of antibiotics that work better for C. diff compared to some of the other antibiotics.

What we discovered over time is that even though these antibiotics could be effective in treating C. diff infection, they actually increase the risk of having another infection because the very first infection happened because of use of antibiotics. So then we use the antibiotics to treat the infection of C. diff, but that exacerbates the imbalance of good versus bad bacteria, leading to risk of another infection.

So, if we talk in percent risk, if a person has a C. diff infection for the first time in their life, there's about a 25% chance that they will have another one. But if they get treated for that other one with antibiotics, the chances of having another one is about 40%. And if you have C. diff two times, the chances of getting a third is about 60%, which is really high.

So it's very important to kind of understand that we think the antibiotics not only help treat, but behind the scenes, it may actually exacerbate the problem in the long term.

Host Amber Smith: So it doesn't sound like it's the best solution.

Aamer Imdad, MBBS: Indeed.

Host Amber Smith: Is that what prompted you to consider or look at stool transplants?

Aamer Imdad, MBBS: Indeed. Stool transplant helps us to break that cycle, where there is an imbalance of good bacteria versus bad bacteria. There's a term called "dysbiosis" for that. Dysbiosis happens when you use antibiotics for any reason, and that dysbiosis can increase the risk of C. diff infection, and once C. diff infection gets treated with antibiotics, that dysbiosis continues to worsen.

Fecal microbiota transplantation, or stool transplantation, reverses that dysbiosis because we essentially take the stool from a healthy person who does not have dysbiosis, and we transplant that to a patient who seems to have dysbiosis and is getting these C. diff infections because of that.

Host Amber Smith: That's very interesting.

So, healthy people have a microbiome that's " even" -- you have good bacteria and bad bacteria, but they're in a better state?

Aamer Imdad, MBBS: Yeah, this area of research is expanding, and we're getting to know more and more about how the microbes in our body kind of interact with us.

We have bacteria in our gut. We actually have fungi in our gut. We also have viruses in our gut, as well, that live very happily with our body and not only live happily, but actually produce a lot of useful things that really help our body do its functions. Some of the bacteria, for example, are involved in some of the vitamin productions, hormone productions in the gut.

What has been noticed over time is that if there is an imbalance, either in terms of the number of the good bacteria versus bad bacteria, the type of good bacteria versus bad bacteria, and then an absolute ratio between them.

So, we are working more and more to get to know exactly what kind of imbalance would increase the risk. But initial data does show that at least for risk of C. diff infection, there is a very noticeable imbalance of bacteria in our gut that increases the risk and gives the opportunity for C. diff to grow and cause the C. diff-associated diarrhea.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith.

I'm talking with Dr. Aamer Imdad. He's an assistant professor of pediatrics at Upstate, where he specializes in nutrition and pediatric gastroenterology, and we're talking about research he published recently showing that stool transplants do a much better job treating C. diff infections than the commonly used antibiotics.

So can you tell us about the study you did?

Aamer Imdad, MBBS: We did a study called a systematic interview and meta-analysis, under Cochrane Collaboration.

Cochrane Collaboration is a group of experts that help synthesize all the available evidence for a particular health care intervention. Cochrane Collaboration helps produce the Cochrane Reviews that are in Cochrane Library, and we all have access to that library. It is considered the gold-standard piece of evidence synthesis that typically leads into a final say in how the clinicians are going to practice.

So, for example, our work from these two Cochrane Reviews will be used by American Gastroenterology Association to issue their guidelines. It feeds into how the clinicians practice.

So, the process starts with a clinical question. We, as clinicians, were very interested to know that if patients are getting recurrent C. diff infection, can the stool transplant be helpful?

So, scientifically, in order to answer that clinical question, the best type of evidence comes from randomized control trials where patients with that particular condition are randomized into either, say, in this case, a fecal microbiota transplantation, or stool transplantation, versus the standard of care.

So, once the results are available from more than one randomized control trial, they can be synthesized quantitatively or mathematically into meta-analysis, giving us a summary estimate that will indicate the final efficacy, or effectiveness, of the intervention to help us guide our clinical practice.

In this particular study, we found that fecal microbiota transplantation, or stool transplantation, helped resolve the recurrent C. diff infection more often than the standard-of-care antibiotics.

Host Amber Smith: So, based on your findings, would patients with C. diff infections be candidates for stool transplants, or would you only recommend it for someone who has recurring C. diff infections?

Aamer Imdad, MBBS: This is a very good question and a very important one to differentiate. Our study looked at prevention of recurrent C. diff, so the stool transplant will be done in between the episodes. So, for example, if a patient had one episode of C. diff, and then they had another one, and then they had another one, and it keeps happening, typically within one to two months of the previous infection.

Not only that, it can cause illness, obviously it can also affect the quality of life in terms of the number of days somebody could be sick, or they could be admitted (to a hospital) because of the infection. So, the stool transplant is helpful to break that cycle and is done in between the episodes, when the patient is not having active symptoms.

Host Amber Smith: So, at this moment, are stool transplants readily available, and does health insurance pay for them for this?

Aamer Imdad, MBBS: There are very important advancements that have happened over the last few weeks, actually. Historically, there were stool banks in the country that were collecting the stool specimens from the donors, screening them for common infections and then freezing them and then transporting them to the facilities where they could be transplanted.

And Upstate is one of those sites, and I myself, and my colleagues here in pediatrics and in adult gastroenterology have performed the stool transplant. Now, more recently, FDA has approved a stool transplant product. I won't take the name here, but it was approved, that could be delivered via enema, and because it is FDA approved, it will most likely be covered by insurance as well.

Host Amber Smith: I was going to ask you how, practically, the stool transplants are done. So there are stool banks, so people make donations, and then the stool is processed. Is each stool transplant from one person, or is it blended from a bunch of people?

Aamer Imdad, MBBS: So, for the purpose of treating recurrent C. diff infection, a stool coming from a single donor is effective in most of the patients, and we typically do not have to mix the stool from multiple donors. There are some additional studies going on, and we have looked, in a separate, systematic review and meta-analysis, on the effectiveness of stool transplant for treatment of inflammatory bowel disease.

And over there it seems like stool donation from multiple donors will be required, for them to be pooled, to increase the richness and diversity of the bacteria in the stool. And it might have to be given more often compared to a one or maximum two to three doses for treatment of recurrent C. diff. So for the purpose of treating recurrent C. diff, it's typically a single-donor stool specimen, and that is transplanted into a single person.

Host Amber Smith: And you mentioned that it's transplanted via enema. Are patients hospitalized for this, or is that done in an outpatient setting?

Aamer Imdad, MBBS: Stool transplant can be done in multiple ways. So now there are actually capsules or "poop pills," that could be taken. It can also be administered through a nasogastric tube, which goes from the nose into the stomach, or nasoduodendal tube, which goes from the nose into the first part of the small bowel.

It could also be given via the enema.

And historically, it was initially started by giving it via colonoscopy, in which a colonoscope is taken to the very start of the large bowel. And it is distributed from start of the large bowel towards the end of it.

The pills and the enemas obviously can be done as an outpatient. For a colonoscopy, the patient typically has to come to the hospital, or at least an outpatient GI (gastrointestinal) clinic, where the colonoscopies could be performed.

Host Amber Smith: How quickly might a patient feel better after this?

Aamer Imdad, MBBS: It is a very effective therapy.

The key here is to understand that it is done when the patient is asymptomatic. So, the efficacy of a single microbiota transplantation is somewhere around 75%. So, if the patients have another recurrence, and they get a second transplant, the efficacy goes up to 90 to 92%, and there are very few interventions in medicine that are as effective as fecal microbiota transplantation for treatment of recurrent C. diff.

Host Amber Smith: Are there any side effects to watch out for from the transplant?

Aamer Imdad, MBBS: Remember, the stool is a donor-based stool specimen, and obviously, it not only has the good bacteria, it also has the bad bacteria. So there is a risk of transmission of infection, and FDA has issued some warnings about the possibilities of transmission of infection, including the COVID-19 infection, the monkeypox infection, which are both rare, but then there are other types of infection, and especially the patients who are immunocompromised, severely immunocompromised, they could acquire infection from the donor-based stool.

So, as part of the processing of the stool, all of the stool specimens are screened for common infections. And not only that, the donors are also screened for other health conditions. For example, if the donors have diabetes or hypertension or any other chronic disease, their stool will not be taken as a donation for the transplantation.

Host Amber Smith: So, it sounds like there's a structure to it, like the blood banking in the U.S., where the blood is surveyed before it's used.

Aamer Imdad, MBBS: It is.

It is less regulated compared to blood donation, but we're probably moving towards that. Currently, there is not a very universal donor-screening protocol that we have, but we will most likely see that there will be guidance from organizations like FDA to help establish and run the stool banks as we gather more and more evidence for the usefulness of fecal microbiota transplantation for not only C. diff, but other conditions as well.

Host Amber Smith: I was going to ask if stool transplants can be used to treat C. diff, are there potentially other uses, too?

Aamer Imdad, MBBS: Indeed there are, and there is a lot of interest in studying the stool transplantation for other health conditions. And we as gastroenterologists are very interested in its use for treatment of inflammatory bowel disease.

So we did a sister publication on it where we looked at patients who have ulcerative colitis, which is one subtype of inflammatory bowel disease, and patients who are having active disease, can the stool transplant be used for their treatment?

And the data is actually very promising. It's not where we can recommend it for change of practice, but more and more studies are being conducted, and over the next two to five years, it is likely that we will have some sort of a conclusive evidence to say if the stool transplantation can be used for the treatment of active ulcerative colitis.

People are also looking at other conditions, like irritable bowel syndrome, obesity and beyond. Frankly, a lot of basic science data is finding association on how our gut microbes interact with our rest of the body. And a lot of scientists now think that some of the conditions that we experience in our body could be associated on how, and what kind of, microbes do we have in our gut.

Host Amber Smith: Well, this is very interesting work. I appreciate you telling us about it, Dr. Imdad.

Aamer Imdad, MBBS: Absolutely. My pleasure.

Host Amber Smith: My guest has been Dr. Aamer Imdad. He's an assistant professor of pediatrics, specializing in nutrition and pediatric gastroenterology at Upstate. I'm Amber Smith for Upstate's "HealthLink on Air."

Next on Upstate's "HealthLink on Air," a neurologist explains a new era in epilepsy treatment.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

Neurologists and neurosurgeons believe they can help patients who have uncontrolled seizures with regenerative cell therapy implants. And the biotherapeutics company behind this new treatment says the first two patients to try it have seen their seizures reduced by more than 90%. One of those patients was treated at Upstate, and today I'm talking with one of the patient's physicians, Dr. Robert Beach. He's a professor of neurology and chief of epilepsy at Upstate. Welcome back to "HealthLink on Air," Dr. Beach.

Robert Beach, MD, PhD: Oh, thank you very much, Amber.

Host Amber Smith: Now, Neurona Therapeutics is the company behind this new treatment, and it has a national clinical trial underway. Data from the first two patients was presented at the American Academy of Neurology this spring. What can you tell us about how these patients are doing?

Robert Beach, MD, PhD: So, to start off, the very first patient in the world was our patient here, who received the cells 11 months ago. He's done very well, as has the other patient who's had them.

He was having about 30 seizures a month, the patient here. And he has had an average of around one a month over the last several months. The patient in Oregon also had a similar improvement, although not exactly the same.

Host Amber Smith: So it sounds like really substantial improvement.

Robert Beach, MD, PhD: Oh, yes. Really more than we anticipated even.

Host Amber Smith: So this regenerative cell therapy implants, these are being tried as a treatment for someone with epilepsy that's resistant to medication. Is that right?

Robert Beach, MD, PhD: Yes. And a very specific class of those patients, because we're talking about putting a very tiny amount of cells in a very specific place. And one of the best known and characterized sources of seizures that are intractable in humans is those that come from the hippocampus or the medial part of the temporal lobe.

Those have traditionally been treated first with medicine. Usually about a third of them are not controlled with whatever medicines in combination are used. And those have been treated for about 60 years now with what's called an anterior temporal lobectomy, which is where the hippocampus and a fair amount of adjacent tissue is removed.

And this has been quite successful. About 75% or 80% of these patients will have very few or no seizures. So the traditional surgery is a fairly large area of tissue. And there's been attempts over the years to take out smaller amounts of tissue, which is technically more difficult, but there's been long-term attempts to develop tools that might give a more precise treatment with less resection of tissue and less side effects. One of those approaches has involved implanting neurons.

These cells that are produced by Neurona Therapeutics are cells that are able to be made into very specific cells. Now, there's the ability to take stem cells, differentiate them into specific cell types, and then to save them in very specific parameters so that they're always the same in every sample. For this treatment of epilepsy, the cells are differentiated into inhibitory cells, and those are cells that release GABA or gamma-aminobutyric acid. It's a neurotransmitter that's used by inhibitory neurons to signal other neurons.

The cells that produce it are primary what are called interneurons, and they usually involve modulation of the major cells, the excitatory cells, both input and output. It's felt that much of the underlying cause of epilepsy has to do with inadequate inhibition or excess excitation.

Host Amber Smith: Well, let me ask you, when these implants arrive, before they're put into the patient, the cells are already part of the implant?

Robert Beach, MD, PhD: So the cells are a sample of a specific number of these differentiated inhibitory neurons in a liquid solution that are frozen into multiple different aliquots (portions) that are virtually identical. After they come here from the company in San Francisco, they are characterized, tested for viability and contaminants. And, then once that's all established, they're put into a cannula (thin, hollow tube) that is the delivery system.

The hippocampus is deep in the brain, and the best way to get to it without disturbing other tissues is using a long, tiny cannula that goes into it from the back of the brain. Once this cannula is in place, very tiny amounts of the cells are released at four or five different places and then are allowed to integrate with the patient cells.

Host Amber Smith: I'm envisioning this cannula like a tube. Is it like a skinny straw?

Robert Beach, MD, PhD: It's like a needle, much smaller than a straw, but it's the same principle, I guess.

Host Amber Smith: OK. So how soon after the implant is in place would patients notice a reduction in seizures?

Robert Beach, MD, PhD: Well, we don't really know. The initial hypothesis was that it would take integration to the cells, which could take months. However, we saw change in less than a month in both patients. So we think that it's not just integration, but possibly release of the inhibitory GABA even before the cells are directly interacting completely with other cells.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith. I'm talking with Dr. Robert Beach about a new procedure for treating severe forms of epilepsy.

So other than the improvements with the reduced number of seizures, are you seeing other improvements in these patients?

Robert Beach, MD, PhD: Well, it's a bit early, but in our patient we did notice some improvement in some memory measures. And also we were able to lower his medications, which were at pretty high doses prior to the implant. And I think some of his benefit comes from just reduction of the side effects of the high-dose seizure meds.

Host Amber Smith: That's encouraging. So what happens to the implant over time?

Robert Beach, MD, PhD: Well, we think it integrates, based on rodent studies. It can be demonstrated to persist for many months after implantation and appears to be stable. We assume that would be similar in the human, but we haven't really demonstrated that yet.

Host Amber Smith: Are there any negative side effects that you've become aware of?

Robert Beach, MD, PhD: I think the side effects that exist are related to the fact the patient has to be immune suppressed, and some of these immune suppressant drugs have side effects. And of course, they put the patient at increased risk for some infections -- which are generally carefully guarded against and has not happened in our patients -- but that's a risk.

Host Amber Smith: Well, I know it's still early, but does this seem to you like it's the dawn of a new era in epilepsy treatment?

Robert Beach, MD, PhD: Well, this is a very singular type of epilepsy, but it is one of the most common intractable types. And I think this will definitely develop into a treatment option that rivals the other ones and may be proved superior over time.

Host Amber Smith: As you were describing earlier, it's for a specific type of epilepsy that starts from a specific area of the brain, but now that it looks like it's beneficial for those patients, do you think it might be tried in patients that have epilepsy that starts in other areas of the brain?

Robert Beach, MD, PhD: I think so, as long as it's in a small area that can be very precisely identified, because we are only putting in a very small number of cells. To put in a large amount might cause some imbalance in the overall network. But there are other seizures that come from similar foci that can be fairly similarly characterized.

Host Amber Smith: Now the patients we're talking about are adults. Is that right?

Robert Beach, MD, PhD: Yes. This is only for adults so far.

Host Amber Smith: In the future, would it perhaps be looked at for children as well?

Robert Beach, MD, PhD: If it's successful it would definitely be looked at for children, yes.

Host Amber Smith: Now, could it be a strategy to treat milder forms of epilepsy?

Robert Beach, MD, PhD: Possibly, but the seizures that are most difficult to control are the ones that at least are most logical at this point.

Host Amber Smith: Can you think of any other neurological diseases that might be helped by regenerative cell therapy?

Robert Beach, MD, PhD: There's been trials of similar cell implants or different cell implants, I should say, in Parkinson's disease patients for more than 25 years. The success rate has not been as clear. The area where the cells need to be put for Parkinson's is perhaps a little less well-identified than the seizures. I think the more precise information on treating Parkinson's with similar cells may well turn out to be effective.

Host Amber Smith: That's good to know. Dr. Beach, thank you so much for making time to tell us about this.

Robert Beach, MD, PhD: Thank you for having me.

Host Amber Smith: My guest has been Dr. Robert Beach. He's a professor of neurology and the chief of epilepsy at Upstate.

I'm Amber Smith for Upstate's "HealthLink on Air."

Here's some expert advice from Dr. Ioana Medrea from Upstate Medical University. At what point should I see an expert about headaches?

Ioana Medrea, MD: About 80% of people have headaches at some point, and the time to see me is when your headaches are interfering with your ability to lead your life. So what does that mean? How would that look like? A lot of people I see have trouble doing their job because their headache is making them have to miss work, or when they're at work, have to step away and not be as productive as they could be.

Another manifestation would be issues with your ability to do your jobs at home, so running errands, cleaning the house, maintaining the house. When you're having significant enough headaches that you're finding yourself avoiding those tasks, that's another sign that it may be time to see a headache specialist.

And the last thing is when it's interfering with your social activities, you are shying away from seeing family, friends, or participating in things you would normally participate in because your headaches are severe enough that you don't want to leave your house. That would be another sign that you need to see someone for your headaches.

Host Amber Smith: You've been listening to neurologist Ioana Medrea from Upstate Medical University.

And now, Deirdre Neilen, editor of Upstate Medical University's literary and visual arts journal, The Healing Muse, with this week's selection.

Deirdre Neilen, PhD: Eric Machan Howd teaches professional and technical writing at Ithaca College. His new collection of poetry, "Universal Monsters," has just come out from the Orchard Street Press. He sent us a beautiful celebration of a man's life, told through a series of nautical images. Here is "The Sailor's Hitch":

The first time he came home

from surgery he found it difficult

to rise out of the waterbed. His stomach

muscles, though tightly woven,

were severed to get at what darkness

was swimming inside of him, so he brought

some old rope out of the cellar, looped

one end around the post at the foot

of the bed, and formed the other

into a handle. Each morning, he'd pull

himself up out of the mattress,

far enough to swing his feet over the edge

and push off toward the window, the fresh

air of springtime, the distant smell of salt water.

He grew up with sand between his toes, his soles

hard callused from pounding beach

and boardwalk. He tied himself

to the tides and shore, to the silent

father who returned home from war,

to the tired mother who punished

with her glance, to the beached whale

of his youth that appeared above the fold

of the Sunday issue

of the Asbury Park Press,

to anything that was anchored.

He knew the best knot for every

situation: the binding half-hitch,

the fishing line's blood knot

the secure icicle hitch, the strong water bowline. He knew

how the barrel hitch was best

for suspending objects, how the slip

knot was not a noose, and how the monkey's

fist needs to be stuffed into crevice to root

the climber's line. He knew of pull

and slack and broke his back

on roof's edge hauling bundles

of shingles from ground to pitch with tow line.

He fished for the end of the rope with boat

hook to pull his family to dock

mooring after a day, swimming and steel

gray Atlantic waters and hitched to the salty

ends to the slip's corroded horn cleats.

He eventually let his boat go

and dug an in-ground pool, bought a water

bed, and moved closer to Shark River

Inlet, the place where grown-ups warned

their children not to swim with tales

of teeth, the whites of rolled back

eyes, and breeding. He always wanted

to see the darkness inside of the whale

and regretted not using his pocket-knife

to open the one he found on Bradley Beach

as a child, to discover what was beneath skin

and fat and muscle. By the time Hospice came,

he had tied his rope to the living room recliner,

and as he died he reached up

as if to pull another rope we could not

see -- to pull himself up to the ceiling

as he cried Mommy, Daddy, and struggled

to get closer, to pull himself toward the knot,

hand over hand toward his darkness, his light.

Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York.

If you missed any of today's show, or for more information on a variety of health, science and medical topics, visit our website at healthlinkonair.org.

Upstate's "HealthLink on Air" is produced by Jim Howe, with sound engineering by Bill Broeckel.

This is your host, Amber Smith, thanking you for listening.