Uncovering a Viral Link to Parkinson’s Disease with Dr. Barbara Hanson and Dr. Igor Koralnik

Summary

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Podcast Summary

Podcast: Becker’s Healthcare Podcast
Episode: Uncovering a Viral Link to Parkinson’s Disease with Dr. Barbara Hanson and Dr. Igor Koralnik
Release Date: August 18, 2025
Host: Laura Dardo (A)
Guests:

• Dr. Barbara Hanson, Postdoctoral Researcher, Department of Neurology, Northwestern Medicine
• Dr. Igor Koralnik, Archibald Church Professor of Neurology & Chief of Neuroinfectious Disease and Global Neurology, Northwestern Medicine

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Episode Overview

This episode delves into groundbreaking research from Northwestern Medicine that investigates the possible viral triggers of Parkinson’s disease (PD), specifically the discovery of a strong association between human pegivirus and PD pathology. Dr. Barbara Hanson and Dr. Igor Koralnik share their recent findings connecting certain viruses to the brains of people with Parkinson’s, discuss how genetic factors might interact with viral presence, and highlight the broader implications for diagnosis, treatment, and future research around Parkinson’s disease.

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Key Discussion Points & Insights

1. Research Focus and Motivation

• Dr. Koralnik’s lab seeks to understand how viruses affect the nervous system, with a focus on whether viruses may contribute to neurodegenerative diseases like Parkinson’s.
  • “You know that Parkinson's disease is this deteriorative disease of the nervous system affecting more than a million people in the United States...the cause of the disease is unknown for the majority of cases.” (C, 00:50)
• Environmental factors—including viruses—have long been hypothesized as potential triggers for Parkinson’s, given that genetics account for only a minority of cases.

2. Comprehensive Virome Analysis

• The team developed an unbiased assay called “varofind” to search for all known human viruses in postmortem brain samples of PD patients and matched controls.
• Significant finding: While various viruses were found in both groups, human pegivirus was detected exclusively in the brains of PD patients.
  • “There was one species of viruses that existed only in the brain of Parkinson's patient. This is called the human Pegivirus...” (C, 01:49)
• Human pegivirus is generally thought to be harmless and not found in the brain, making its presence in PD brains particularly startling.

3. Findings and Significance

• Out of 10 PD donors, 5 had human pegivirus in their brain tissue. By contrast, none of the age and sex-matched controls tested positive.
  • “We identified in 5 out of 10 of the PD donors the presence of human pegivirus... we did not find it in any of the control donors in this population.” (B, 02:53)
• Historically, human pegivirus has not been linked to any clinical symptoms or to being part of the healthy brain virome.
• Association with Parkinson’s was stronger than with other neurodegenerative conditions (ALS, MSA, AD, HIV, etc.) previously studied by the group.

4. Implications for Pathology and Detection

• In addition to brain tissue, human pegivirus was found in the cerebrospinal fluid (CSF) of about 30% of PD cases, suggesting potential for in vivo detection.
  • “...not only the virus was present in the brain...but also in 30% of them, we found the virus in their cerebrospinal fluid.” (C, 04:29)
• Presence of the virus correlated with differences in pathology—though clarification was made that increased pathology observed was for Alzheimer’s (AD) markers, not Parkinson’s, due to the recruitment through an AD cohort.
  • [Clarification] “These individuals were actually recruited through an AD cohort and the only measures that we have are actually measures of AD pathology.” (B, 06:42)

5. Interaction Between Virus and Genetics

• Analysis using blood samples and datasets from the Parkinson’s Progression Marker Initiative (PPMI) showed that immune responses to pegivirus varied depending on whether PD patients carried the LRRK2 mutation (a known genetic risk factor).
  • “We saw a dichotomy between individuals who have PD and carry a LRRK2 mutation and those who have PD but don’t carry that LRRK2 mutation.” (B, 09:10)
• Differences centered around an immune signaling molecule, IL4, which may play an unexpected role in modulating disease progression.

6. Potential for Therapeutic Repurposing

• Human pegivirus is closely related to Hepatitis C virus (HCV), for which effective medications already exist.
• If findings are validated, HCV therapies could potentially be repurposed to target human pegivirus in PD patients.
  • “It would be possible to think that those medications that could affect the hepatitis C virus in the liver could be also repurposed to...target the human [pegivirus] in the brain.” (C, 05:35)

7. Next Steps and Broader Research Directions

• Ongoing work includes:
  • Expanding the study to new brain samples from Australia and other sources to validate findings outside the US.
  • Investigating localization of the virus to specific brain cell types, such as oligodendrocytes, via neuropathological methods.
  • Testing in silico how anti-HCV drugs might bind or inhibit human pegivirus.
  • Seeking collaborations with researchers and pharmaceutical companies.
  • “...the more the merrier. Obviously, this is a new field of investigation and I think that we need to attract more people to this field, including pharmaceutical companies...” (C, 12:52)

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Notable Quotes & Memorable Moments

• On the nature of the discovery:

  • “This is really not something that we particularly expect to be associated with any pathology...” (B, 03:08)

• Potential for treatment:

  • “There are treatments but no cure. What we find is also interesting is that this human pegivirus is a close relative from another virus called Hepatitis C virus...If the finding...is confirmed and expanded...then it would be possible to think that those medications...could be also repurposed...” (C, 05:15)

• On the interplay of genes and environment:

  • “You’ve got this interaction between the environment and the genetic background where some individuals may be infected...and maybe developing very, very different responses to it that could have some interactions with that, the development of Parkinson’s disease...” (B, 10:38)

• Call for collaboration:

  • “First, I'm happy if people are interested in our study and want to collaborate with us. Maybe they have unique samples...the more the merrier...I think that we need to attract more people to this field...” (C, 12:52)

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Important Timestamps for Key Segments

• [00:50] – Dr. Koralnik introduces the study’s motivation and background
• [01:49] – Discovery of human pegivirus association with PD brains
• [02:53] – Dr. Hanson details specific findings from brain tissue samples
• [04:29] – Detection of the virus in cerebrospinal fluid; potential clinical implications
• [05:35] – Discussion of antiviral therapy repurposing prospects
• [06:42] – Clarification on observed pathology measures (AD vs PD)
• [08:21] – Interaction with genetic mutations (LRRK2) and immune signaling (IL4)
• [12:52] – Appeal for collaboration and description of ongoing/next studies

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Conclusion & Future Directions

The research by Dr. Hanson and Dr. Koralnik represents a major step toward understanding how environmental factors—specifically viral infections—may interplay with genetics to influence Parkinson’s disease development and progression. Their discovery of human pegivirus in the brains of PD patients challenges assumptions about the role of “harmless” viruses and opens opportunities both for new diagnostic methods and for exploring the repurposing of existing antiviral therapies. The team’s openness to collaboration and commitment to expanding the scientific inquiry set an exciting direction for future neurodegenerative disease research.

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Transcript

[A]

This is Laura Dardo with the Beckers Healthcare Podcast. I'm thrilled today to be joined by Dr. Barbara Hanson, postdoctoral Researcher in the Department of Neurology at Northwestern Medicine in the Karalnik Laboratory, and Dr. Igor Koralnik, who is the Archibald Church professor of Neurology and Chief of Neuroinfectious Disease and Global Neurology at Northwestern Medicine. Dr. Hanson, Dr. Karalnick, thank you so much for joining us on the podcast today.

[B]

Thank you for, thank you very much for having us.

[A]

Thank you both for being here. I'm really excited for our conversation and, you know, looking forward to learning more about what you're doing at Northwestern Medicine and particularly your research. I know you're looking into some of the triggers for Parkinson's disease and finding out different things that can be really beneficial for people with Parkinson's disease. So I'll start off here. Can you tell me a little bit about your research and some of the cool things that you've been doing at Northwestern Medicine?

[C]

Certainly. So my laboratory is interested in general on how viruses affect the nervous system. And so we in this particular project wanted to figure out whether viruses may affect also the pathogenesis of Parkinson's disease. So you know that Parkinson's disease is this deteriorative disease of the nervous system affecting more than a million people in the United States. And few cases have been linked to genetics. But for a majority of case, the cause of the disease is unknown. But it's been hypothesized for a very long time that environmental factor such as toxins, nutrition or viruses may be at play. So we devised an unbiased assay in my lab to look for not only for one or two viruses, but the entire virome, all viruses known to affect humans called varofind. And with this assay called varofind, we looked in the brain post mortem brain sample from a group of Parkinson's patients for the presence of any viruses compared to a group of controlled individual who passed away but had no Parkinson's or no specific disease. And what we saw in this pilot study is that there were viruses in both brain cell example from Parkinson's and also control patients. But there was one species of viruses that existed only in the brain of Parkinson's patient. This is called the human Peggy virus, which is otherwise a virus thought to be harmless, can be found in the blood sample from normal donor and is not known to find to be found in the brain. And now I can let Barbara describe the findings in this study.

[B]

Sure. So basically, as Dr. Koralnik stated, we looked at postmortem brain tissue samples from a number of PD patients and age and sex matched controls, and we identified in 5 out of 10 of the PD donors the presence of human pegivirus to some extent, whereas we did not find it in any of the control donors in this population. As he said, that's substantial because this is really not something that we particularly expect to be associated with any pathology because it is has not been found to show any clinical symptoms for people who are infected for years or decades in the U.S. and moreover, it's not something that we particularly expect to be a part of the normal healthy brain virome. So it was pretty substantial that we found it in that high a population from this cohort study. So in addition, we've looked at a number of different neurodegenerative diseases prior to Parkinson's disease, and this was the strongest association that we've found with any virus from the neurodegenerative diseases that we've looked at in the past, including ALS, MSA, AD, HIV, etc.

[A]

That's fascinating to hear and truly interesting to get a sense of your research and how you have made this finding. Now, as you're kind of taking a look at the results and seeing this potential interesting finding here, what does that mean for patients and how are you looking at that is a trigger for Parkinson's disease.

[C]

So certainly. So first people need to realize that it is a post mortem study where we have one snapshot in those brain sample after patient died from Parkinson's disease. Right. But what we found is that not only the virus was present in the brain of half of the people with Parkinson's disease, but also in 30% of them. We found the virus in their cerebrospinal fluid. So there was potentially way to detect the virus also during the lifetime of the patient. In addition, as Barbara mentioned, the presence there was not only the presence of the virus in the brain, but we also found that it was associated with a worse pathology associated with Parkinson's in those Parkinson's patients who had the virus versus those who did not have the virus. And also Barbara did the complex gene expression analysis, founding that there was a dampening of the immune signaling coming from the brain from Parkinson's patient who had the piggy virus in them. So this is really something that we think is opening a new field of investigation in this disease for which there otherwise is, there are treatment but no cure. What we find is also interesting is that this human pegivirus is a close relative from another virus called the Hepatitis C virus, hcv, for which medications are readily available to target the virus in the liver. So obviously, if the finding that we have in this pilot study is confirmed and expanded, which we are in the current in the way of doing, then it would be possible to think that those medications that could affect the hepatitis C virus in the liver could be also repurposed to TRIG to target the human piggy virus in the brain.

[B]

So I do want to clarify something a little bit here. Dr. Karalnik suggested that we saw an increase in PD pathology in the brains of these individuals. So that's not entirely accurate. So these individuals were actually recruited through an AD cohort and the only measures that we have are actually measures of 80 pathology. So what we see in these individuals is that there was an increase in BRA staging associated with AD pathology in the individuals who have the human Peggy virus. So this is another reason that it's extremely important that we're able to expand on these findings because, you know, these, these individuals don't have good pathological markers for the PD pathology from, from the index cases in the brain tissue. So we're activ for additional cases that we can look at that could then be correlated again further with the actual Lewy body presence, et cetera, the changes in tyrosine hydroxylase expression in neurons, et cetera.

[A]

That's fascinating to hear and I really appreciate the in depth description, explanation of what your research is finding because it's so important for so many people out there who are every day living with Parkinson's and their relatives, as well as those who may, may be diagnosed in the future. So when you look at just in general, some of the different connections between your research and the genetic mutations that you're seeing, what are some of the implications of that interaction for future research or treatment, and what do you see as being the next steps to your research as well?

[B]

So basically what we saw from the periphery, because we don't have genetic information from the brain tissue donors, but we did match this with blood tissue samples from individuals who've been recruited through a very large, long standing cohort study called the Parkinson's Progression Marker Initiative, which is hosted by the Michael J. Fox Foundation. So the PPMI database allowed us to mine a very large number of PD cases and by just looking at their RNA SEQ data. So this is sort of the whole transcriptome sequencing, we were able to identify individuals who were infected at the time of blood donation. And we were then able to sort of correlate changes in expression of genes with the presence of the virus and also with the, the titer of the virus over time. And what we saw was that there was a dichotomy between individuals who have PD and carry a LRRK2 mutation and those who have PD but don't carry that LRRK2 mutation. So, so individuals who essentially are idiopathic for, for, for Parkinson's disease, they have genetic cause. And what we saw was there was a very substantial difference in the way Those individuals, the LRRK2 carriers and those who did not carry LRRK2 mutations responded to the virus. And essentially it was around a, a, an axis that involves a, an immune signaling molecule called IL4. And IL4 is interesting because it's not really something that has been known to be associated with Parkinson's disease. However, in the context of Parkinson's disease, it has been noted that IL4 changes in the brain do correlate with the development of pathology, but in an interesting way it's, it's con, it's highly context dependent. So we're not entirely sure what those findings mean at this time. But having seen that, we do think that, you know, this is yet sort of another arena wherein you've got this, as, as we mentioned early on, where you've got this interaction between the environment and the genetic background where some individuals may be infected with this pathogen in specific or maybe other pathogens, but specifically human PEGGY virus in this context and maybe developing very, very different responses to it that could have some interactions with that, the development of Parkinson's disease or the continuation of pathology with Parkinson's disease. So again, that's really something that we're continuing to look at. So as I mentioned, we don't really have information about the genetic background of the people for whom we had brain tissue samples available, but we were able to perform a very similar RNA SEQ experiment. So from those brain tissue samples, the remaining tissue samples that we had, we, we performed whole transcriptome sequencing. So basically taking all of the RNA which was expressed at the, at autopsy and, and we're able to map that to the human genome and see what genes are being expressed and what pathways are activated or inhibited in those individuals. And what we saw in the brain tissue was a recapitulation of what we saw in the periphery, wherein IL4 signaling did seem to be substantially important within the model of how PEGGY virus was interacting with those PDF patients in the brain.

[C]

So basically, in summary, there is seem to be a complex interaction between the virus genetics and the pathogenic process in the brain of Parkinson's patient.

[A]

Got it. That's really helpful to know and understand exactly what is going on here and then think about of course Parkinson's disease in research as well as treatment a little bit differently in the future. I'm curious, you know, what would you like to other physicians and healthcare professionals to know about this research and how you're looking to continue to work towards additional answers in the future? I think, you know, so many physicians as well as clinicians in general come across patients with Parkinson's or those who are maybe in early stages and it would just be interesting for them to understand what this all means for them as well as the technology that, you know, you use in order to come to this conclusion.

[C]

Definitely. First, I'm happy if people are interested in our study and want to collaborate with us. Maybe they have unique samples from brain of Parkinson's patient. Maybe they have different assay that they could be testing and the more the merrier. Obviously this is a new field of investigation and I think that we need to attract more people to this field, including pharmaceutical companies who are making medications for Hepatitis C virus, who may be interested also to collaborate or support our effort to see if those could be repurposed maybe one day for the piggy virus to help some patients with Parkinson's disease. And as far as we are concerned, we are now looking at doing computer modeling in silico with the known anti Hepatitis C medication to see how they could be binding or inhibiting the human Peggy virus the same way they do for the Hepatitis C virus. So this is a study that is ongoing in my laboratory as well together with Dr. Hanson. And we are actively trying to get brain sample from Parkinson's patients who are in a brain bank in Australia as well as control to see if this population of patient outside of the US we see the same finding. We are expanding our studies in the contralateral brain sample from the patient. From the first study what we got was fresh frozen sample and the other hemisphere of the brain has been fixed in formalin and embedded in paraffin. So together with the neuropathologist at Northwestern, Dr. Jamshidi and Dr. Castellani, we are going to look at all the sample that we have available from all the locations in the brain of the patients with Parkinson's end control to try to expand our initial findings under the microscope where in two of those patients we found that the virus was express in oligodendrocytes, the white matter producing cells and not in the control sample. So this is what we're doing currently. Obviously, there may be other ideas, and we're again happy to collaborate with anybody who may be interested.

[A]

That's fantastic to hear. Thank you both so much for joining us on the podcast today. This has been truly an informative and fun conversation to have, and I look forward to connecting with you again soon.

[B]

Thanks very much for having us.

[C]

It was a pleasure.