What if you could tell ahead of time who needed how much pain relief?
What if you could avoid administering opioids to those with the highest risk of addiction, even if they didn’t already know for themselves?
What if you could help ease the pain of a patient in need and be sure that you’ve made the right call?
Brian Meshkin of Proove Genomics shares his journey from personal tragedy to pioneering a scoring system that helps clinicians assess pain relief needs based on genetic profiles. Discover how this innovative approach aims to mitigate the opioid crisis by identifying patients at risk of addiction and personalizing pain treatment. Join us for an insightful discussion that blends science, compassion, and the urgent need for change in pain management.
Find out more at https://proove.com/
Image Source: Adobe Stock Images / whyframeshot
Transcript:
00:00:05 Will Mountford
Hello, I’m Will.
00:00:06 Will Mountford
Welcome to Research Pod.
00:00:08 Will Mountford
We’ve talked about a lot of research over the course of this podcast in orbit of today’s topic, genetics and health, pain and recovery, opioids and the social crises around them, innovation and perseverance.
00:00:22 Will Mountford
Today’s discussion brings all those aspects together into a unified focus.
00:00:27 Will Mountford
What if you could tell ahead of time who needed how much pain relief?
00:00:31 Will Mountford
What if you could avoid administering opioids to those with the highest risk of addiction, even if they didn’t already know for themselves?
00:00:38 Will Mountford
What if you could help ease the pain of a patient in need and be sure that you’ve made the right call?
00:00:44 Will Mountford
These questions may just be answered over the course of this episode as we hear from Brian Meshkin of Proove Genomics, a scoring system that aims to help clinicians better understand the genetic root of their patient’s pain.
00:01:00 Will Mountford
And joining me to talk about his work in Proove Genomics and everything leading up to that today, Brian Meshkin.
00:01:05 Will Mountford
Hello there.
00:01:06 Brian Meshkin
Hi, Will.
00:01:06 Brian Meshkin
How are you this morning?
00:01:07 Will Mountford
It’s A frosty one.
00:01:08 Will Mountford
But for now, we are talking about genomic screening and Proove Genomics.
00:01:11 Will Mountford
So let’s start off with a little bit of background on you and what has led to the founding of the company, because this hasn’t come from nowhere.
00:01:19 Will Mountford
You have quite a story to lead to us today.
00:01:21 Will Mountford
Could you walk me through some of that?
00:01:22 Brian Meshkin
Sure, I’d be happy to.
00:01:23 Brian Meshkin
I guess they would probably diagnose me as what they would
00:01:25 Brian Meshkin
call a social entrepreneur.
00:01:27 Brian Meshkin
I am someone who, throughout my life’s journey, have tried to find purpose in doing things from various different perspectives to be able to make the world a better place, to be able to help save lives, to extend the quality of life.
00:01:39 Brian Meshkin
I kind of learned at a young age that somebody like me, who wasn’t particularly special, I wasn’t born into some big wealthy family, I didn’t have a famous last name, I had a funny last name that I would have to spell for people, but that I could make a positive impact.
00:01:51 Brian Meshkin
When I was 13, a good friend of mine, Chris Kelly, was riding his bike over to my
00:01:55 Brian Meshkin
my home on a windy country Rd.
00:01:57 Brian Meshkin
and tragically was hit by a car right in front of my home and killed.
00:02:01 Brian Meshkin
It was one of those experiences that was really a life-defining moment for me in a bunch of different ways.
00:02:06 Brian Meshkin
Obviously, I had my own issues to kind of work through personally and my relationship with God and trying to understand that injustice.
00:02:12 Brian Meshkin
But I also wanted to prevent something that was so awful from happening to others and had a measure of survivor’s guilt and felt that I had an obligation to do something with my life that would make it meaningful since Chris’s was tragically taken early and mine for some reason was
00:02:25 Brian Meshkin
preserved.
00:02:26 Brian Meshkin
At the time, I thought I wanted to be a lawyer.
00:02:28 Brian Meshkin
I thought that having a high sense of justice somehow equated with the law.
00:02:32 Brian Meshkin
Obviously, I’ve kind of changed in that view going forward in life.
00:02:36 Brian Meshkin
And I put together an effort where we lobbied for and enacted the very first bicycle helmet law for children in the United States in Howard County, Maryland, where I grew up.
00:02:45 Brian Meshkin
And then I did it in the neighboring county.
00:02:47 Brian Meshkin
And it was a different time.
00:02:48 Brian Meshkin
You know, today I’d be ripped apart in the media and on social media.
00:02:51 Brian Meshkin
But back then it was a feel-good story.
00:02:53 Brian Meshkin
And I was on the television and the newspapers.
00:02:55 Brian Meshkin
And so I got a phone
00:02:56 Brian Meshkin
call from a former Surgeon General of the United States at the time.
00:02:58 Brian Meshkin
They wanted to spin a public interest campaign out of Children’s National Medical Center and take the program that I, along with all of my classmates, had built in Maryland involving the law, the public education curriculum, the bicycle safety rodeos with the fire departments and the police departments, et cetera, et cetera, and take this nationwide as kind of a founding project of this organization, which back then was called the National Safe Kids Campaign.
00:03:20 Brian Meshkin
Today it’s called Safe Kids Worldwide.
00:03:22 Brian Meshkin
It’s the largest childhood injury advocacy organization in the world.
00:03:25 Brian Meshkin
And so during my
00:03:25 Brian Meshkin
my high school years, we enacted over 300 similar laws all across the United States.
00:03:30 Brian Meshkin
And so I felt, gosh, someone like me could really make a positive impact in the world.
00:03:34 Brian Meshkin
And that became very life-defining for me.
00:03:36 Brian Meshkin
I’ve tried to do so to the best of my ability, working at large companies like Johnson & Johnson and Eli Lilly.
00:03:42 Brian Meshkin
I had the privilege to serve as an elected official.
00:03:44 Brian Meshkin
I’ve obviously been involved with a lot of nonprofits.
00:03:46 Brian Meshkin
Ultimately, I found, maybe it’s because I can be an impatient person, that the quickest way that I could effectuate change was as an entrepreneur.
00:03:53 Brian Meshkin
And I’ve had the privilege to be able to be an entrepreneur and to go through that stress and building companies, some of which became some of the fastest growing companies in North America, ranked on the Inc.
00:04:03 Brian Meshkin
00:04:04 Brian Meshkin
And the one we’re kind of talking about today really kind of comes down to something that I felt as I had kind of come from pharmaceuticals and also moved into the laboratory space and started building algorithms around how doctors can better
00:04:16 Brian Meshkin
or diagnose and treat.
00:04:18 Brian Meshkin
I saw all around me, whether it was as a kid, it was really tragic when my mom went through this really awful nerve pain that ultimately required spinal surgery.
00:04:26 Brian Meshkin
My wife at the time had chronic pain, and so we were dealing with that.
00:04:30 Brian Meshkin
And I’d seen a lot of people in my life with pain.
00:04:32 Brian Meshkin
We had alcoholism that kind of run in our family, though fortunately I never had to deal with any of that.
00:04:37 Brian Meshkin
And so I saw this increasing issue of the chronic pain crisis emerging.
00:04:42 Brian Meshkin
And so many people that I knew that were in pain, and for some people, Tylenol would work, and for
00:04:46 Brian Meshkin
some people Advil for work and for some people different things would work.
00:04:49 Brian Meshkin
And it just seemed like that could really be personalized.
00:04:51 Brian Meshkin
And then I knew that addiction ran in the family, so there had to be a genetic component to that.
00:04:55 Brian Meshkin
And I started seeing people that were dying from overdoses around me and felt, okay, well there’s got to be a hereditary component to that as well.
00:05:02 Brian Meshkin
And so let’s figure it out.
00:05:03 Brian Meshkin
So back in 2009, I started a company called Proove Biosciences.
00:05:08 Brian Meshkin
We started commercializing our first assay, which was an algorithm combining genetic and non-genetic factors to stratify and identify people who would be at risk for misusing opioids.
00:05:18 Brian Meshkin
And from there, we grew the business.
00:05:20 Brian Meshkin
And around over an eight-year period, we were able to do some really great things.
00:05:23 Brian Meshkin
When you look at the data from the Centers of Disease Control in the United States,
00:05:28 Brian Meshkin
there’s only a three to four year period where the opioid overdose crisis kind of plateaued and flattened and went down.
00:05:33 Brian Meshkin
And that’s when Crew Biosciences was around.
00:05:36 Brian Meshkin
Unfortunately, after eight years, as we were testifying on Capitol Hill and having meetings at the White House and
00:05:42 Brian Meshkin
doing a bunch of different things because of how we were helping save people’s lives.
00:05:46 Brian Meshkin
We had some tragedy befall us that was really unexpected.
00:05:50 Brian Meshkin
We had two former employees file erroneous whistleblower lawsuits against the company.
00:05:55 Brian Meshkin
They were both dismissed by the federal courts.
00:05:58 Brian Meshkin
The government didn’t take them because there was no there there.
00:06:01 Brian Meshkin
But then somehow one of those relators who filed the whistleblower lawsuit was able to get the attention
00:06:06 Brian Meshkin
of a reporter who had been fired from the Los Angeles Times and other newspapers.
00:06:10 Brian Meshkin
He was writing for an online news source, and he wrote two really nasty articles on our company with a bunch of different accusations.
00:06:16 Brian Meshkin
That ultimately resulted in a government inquiry.
00:06:19 Brian Meshkin
It’s amazing.
00:06:19 Brian Meshkin
You go from being the CEO of the year and an earthly angel in the newspapers and all these things for all the good things that you’re doing.
00:06:25 Brian Meshkin
And then all of a sudden, you get hit with these accusations that were completely false of all this wrongdoing.
00:06:31 Brian Meshkin
And ultimately, that resulted in the company having to halt its operations.
00:06:36 Brian Meshkin
We had to take on the Department of Justice, which has unlimited resources, unlimited time, unlimited power.
00:06:42 Brian Meshkin
And it was a long period of time.
00:06:43 Brian Meshkin
It was really hard.
00:06:44 Brian Meshkin
It was job-like personally.
00:06:47 Brian Meshkin
We ultimately had to fire all 300 of our employees, halt the business operations, which was really heartbreaking.
00:06:51 Brian Meshkin
I was having doctors calling me up saying, Brian, when are you going to bring this back?
00:06:55 Brian Meshkin
I have patients that are dying.
00:06:56 Brian Meshkin
And so I felt guilty about that.
00:06:58 Brian Meshkin
We ultimately had to take on the government with all of their bravado and accusations.
00:07:02 Brian Meshkin
I got divorced after 20 years.
00:07:04 Brian Meshkin
It was hard on my children.
00:07:05 Brian Meshkin
It was really, really rough.
00:07:06 Brian Meshkin
And then ultimately, indictments came out with the same type of fraudulent accusations.
00:07:11 Brian Meshkin
And so we had to take that on.
00:07:13 Brian Meshkin
Practically almost bankrupted me having to take on and deal with all of those costs.
00:07:17 Brian Meshkin
But we ultimately prevailed.
00:07:18 Brian Meshkin
The Department of Justice cleared us of any wrongdoing, dismissed all the accusations in the interest of justice, not only for us, but one of our largest clients, National Spine and Pain Center.
00:07:27 Brian Meshkin
Everybody was exonerated.
00:07:29 Brian Meshkin
Then I had to do some soul searching.
00:07:30 Brian Meshkin
What did I want to do next?
00:07:31 Brian Meshkin
So a lot of prayer.
00:07:33 Brian Meshkin
I ultimately felt how I didn’t want to do it because there was a lot of trauma associated with it, but that God wanted me to complete the mission because I spoke with a lot of thought leaders in the field and prayed that I was supposed to do this again.
00:07:44 Brian Meshkin
So I had been now remarried, counseled with my wife about it.
00:07:47 Brian Meshkin
She felt the same way, that it was something that we were supposed to do.
00:07:50 Brian Meshkin
And so we restarted Proove in version 2.0, if you will, as Proove Genomics.
00:07:55 Brian Meshkin
And we brought the technology back and it’ll be interesting to see what this next chapter holds.
00:08:02 Will Mountford
I suppose it is thematic to think of that your story starts with a traumatic incident, that it is to deal with pain, that you’ve gone through so much hurt to get to this point.
00:08:11 Will Mountford
And hurt is ongoing.
00:08:14 Will Mountford
It is something that eventually heals.
00:08:16 Will Mountford
So I’ll ask, Brian, are you in a healed place from all of that now?
00:08:20 Brian Meshkin
That’s a great question.
00:08:20 Brian Meshkin
I would probably make it present tense rather than past tense in the sense that I think there’s always a process of healing that’s happening.
00:08:29 Brian Meshkin
I don’t think I’ll ever fully be healed, to be honest with you, because I’ve kind of come to learn in life that joy and pain kind of are two sides of the same coin in the sense that you can never really let go of the pain without letting go of the joy that happened beforehand.
00:08:46 Brian Meshkin
And so I don’t think it will ever not hurt to have that hurt
00:08:50 Brian Meshkin
there in my heart of what happened before, watching people that I know suffer and those type of things.
00:08:55 Brian Meshkin
But I try to find strength in that.
00:08:57 Brian Meshkin
As someone who’s a Christian, being able to rely upon my Savior Jesus and knowing that He can help heal, He can help carry the cross that is way too heavy for me to hold, because I’m certainly not strong enough to do so, gives me a lot of strength.
00:09:10 Brian Meshkin
And when I know it’s something that God wants me to do, it may not be a straight line.
00:09:14 Brian Meshkin
I’ve certainly learned in life that the line that connects point A to point B is certainly never straight for me at least.
00:09:20 Brian Meshkin
zigzag, but we’re going to complete the mission, and we’re going to make this the standard of care as it was emerging to become.
00:09:26 Brian Meshkin
And we’re going to save a lot of lives, whether it is pain patients that can get the medications that they need that are life-saving for them, or preventing people from getting medications that could be life-threatening for them, which would be totally unexpected because it was prescribed by their doctor, and be able to prevent them from developing what is now the leading cause of preventable death in the United States.
00:09:50 Will Mountford
Part of that resurrection of Proove is the change from Proove Biosciences to Proove Genomics.
00:09:55 Will Mountford
And genomics might be a word that our listeners are becoming increasingly familiar with in terms of the genomics of cancer, the genomics of screening for other sorts of diseases, fertility and so on.
00:10:06 Will Mountford
When it comes to pain, the genomics of pain you mentioned, the heritability of addictive traits and of pain relief seeking.
00:10:14 Will Mountford
How genetic is pain?
00:10:17 Will Mountford
Because to me, pain
00:10:18 Will Mountford
is an instance.
00:10:18 Will Mountford
It is, I stubbed my toe, I scratched my hand, I get hurt, I am in that pain because my body is responding to a stimulus to say, you are in danger.
00:10:27 Will Mountford
Pain is the warning signal of that.
00:10:28 Will Mountford
It’s neurotransmitters.
00:10:30 Will Mountford
Is it that chemically simple from where you stand?
00:10:32 Brian Meshkin
Yes, pain can be a symptom, but chronic pain, when it persists more than 90 days, actually there is a biological change that happens.
00:10:41 Brian Meshkin
And so let’s talk a little bit more about that.
00:10:44 Brian Meshkin
Obviously, pain has now become the nation’s most prevalent and most
00:10:48 Brian Meshkin
expensive health condition, bigger than cancer, diabetes, and heart disease combined.
00:10:52 Brian Meshkin
According to a report that just came out last year from the Centers of Disease Control, amongst the major chronic conditions, cancer, heart disease, diabetes, and pain, pain is the only condition where persistency rates are getting worse, meaning that the current approaches are not reducing the persistency like they are for cancer, diabetes, and heart disease, but they’re failing, and so people are in pain longer.
00:11:13 Brian Meshkin
And so ultimately what happens is there’s a very different change that happens in your immune system
00:11:18 Brian Meshkin
there’s a change that happens.
00:11:19 Brian Meshkin
So for example, when you have an acute pain, like you mentioned, stubbing your toe, or let’s say you and I were playing basketball together and we hurt ourselves with an acute injury, you want your immune system at that point in time to trigger.
00:11:29 Brian Meshkin
But the inverse actually happens when you’re in chronic pain.
00:11:33 Brian Meshkin
The immune system triggering actually makes things worse.
00:11:36 Brian Meshkin
There’s also some neurobiology that changes as well in the way the neurotransmitters move and those type of things.
00:11:42 Brian Meshkin
And so there are changes between that acute stimulus of ouch versus the chronic situation.
00:11:48 Brian Meshkin
But then there actually is not only variability in those who are at risk from going from acute to chronic pain based on genetics, but also in the sensation of ouch in and of itself.
00:12:00 Brian Meshkin
According to published studies, depending on the type of pain for musculoskeletal, which is the most prevalent form of pain, over 50% of all chronic pain is low back pain.
00:12:08 Brian Meshkin
In that situation, about 50% of the variability in that pain is due to genetics.
00:12:15 Brian Meshkin
So Will, let’s say you and I go to the doctor and we hurt ourselves.
00:12:19 Brian Meshkin
It takes months for us to go in to see the doctor because we’re like, we’ll take care of this, put some ice on it.
00:12:23 Brian Meshkin
We’ll take some Advil or some Tylenol.
00:12:26 Brian Meshkin
And eventually, you know, a friend, significant other, whoever says, hey, Will, Brian,
00:12:30 Brian Meshkin
You need to go to the doctor and get this checked out.
00:12:32 Will Mountford
This is the story of my knees, yes.
00:12:34 Brian Meshkin
So by that time, it’s probably already three months, right?
00:12:37 Brian Meshkin
And so now it’s chronic, right?
00:12:38 Brian Meshkin
We’re waving the white flag.
00:12:39 Brian Meshkin
And it’s like, okay, I got to go to the doctor and deal with that rigamarole.
00:12:44 Brian Meshkin
And so you go in there, it’s been hurting for months.
00:12:47 Brian Meshkin
trying to figure out what the heck’s wrong.
00:12:49 Brian Meshkin
And they ask you that silly question.
00:12:51 Brian Meshkin
On a scale from 0 to 10, how would you rate your pain?
00:12:54 Brian Meshkin
Or, you know, if it’s a pediatric situation, I call it science by emoji.
00:12:58 Brian Meshkin
And they do the Wong-Baker scale and they have the frowny faces to the smiley faces and want you to rate your pain.
00:13:04 Brian Meshkin
And that’s literally how we assess the nation’s most prevalent and most expensive health condition.
00:13:08 Brian Meshkin
Something that a kindergartner could do.
00:13:10 Brian Meshkin
Kind of silly.
00:13:11 Brian Meshkin
And your two may be my 8.
00:13:13 Brian Meshkin
Am I saying it’s an 8 because let’s say I live alone?
00:13:17 Brian Meshkin
and I’m lonely and my doctor’s so nice to me and I enjoy going in to see the doctor.
00:13:22 Brian Meshkin
Am I there with my significant other and I’m trying to be brave and so I say it’s a two and it’s really innate.
00:13:27 Brian Meshkin
There are all these things that go into that very subjective self-reporting of pain with smiley faces and frowny faces and zero to 10 scales and not surprisingly when you look at the published literature it says that those are not very accurate and so the only thing they can kind of rely upon is if there are changes in that to determine whether something’s working or not.
00:13:46 Brian Meshkin
But when you
00:13:47 Brian Meshkin
over 50% of that variability between people being a genetic component, it’s a significant issue.
00:13:53 Brian Meshkin
And then on the addiction side, obviously if people are in pain and more people are in pain, then they’re going to prescribe more pain medications.
00:14:00 Brian Meshkin
Opioids have been around for 7,000 years, long time.
00:14:03 Brian Meshkin
They’ve really only become problematic and deadly the last 25.
00:14:07 Brian Meshkin
And you look at those last 25 years, what could we do better?
00:14:10 Brian Meshkin
Well, if we can figure out who is at risk for misusing those opioids, rather than just saying all opioids are bad, which is kind of a silly generalization, then we could do something about it.
00:14:21 Brian Meshkin
And so to that end,
00:14:23 Brian Meshkin
According to the National Institutes of Drug Abuse, which is part of NIH in the United States, as well as the long-form definition of addiction from the American Society of Addiction Medicine, about 50% of the risk for addiction is due to genetic factors, so you’ve got kind of this equation that sits before us.
00:14:40 Brian Meshkin
where 50, 60% of variability in pain is due to genetics, about half, 50% of the risk for addiction is due to genetics.
00:14:46 Brian Meshkin
And I don’t know about you, but if I was taking a test, if I was doing an exam, and I didn’t assess and study 50% of the material for that exam, I’d probably fail it.
00:14:56 Brian Meshkin
would be like flipping a coin, right?
00:14:58 Brian Meshkin
Well, in the patient exam that the clinician is doing, if they’re not assessing and studying 50% of the material, then chances are it’s like flipping a coin for them too.
00:15:07 Brian Meshkin
So we shouldn’t be surprised that we’re failing at
00:15:10 Brian Meshkin
at this miserably if we don’t assess these things.
00:15:13 Brian Meshkin
So thus, if you look at it in the pre- Proove 1.0 years and then the period of time when Proove was around and then the post- Proove years, and now we’re obviously bringing it back, the rates of deaths from pain and the rates of pain skyrocketed and the rates of opioid overdose have skyrocketed no matter what the government has done.
00:15:30 Brian Meshkin
The government first incentivized people to treat pain, then it said all opioids are bad and restricted pain and it just resulted in death.
00:15:37 Brian Meshkin
So it’s pretty simple.
00:15:39 Brian Meshkin
If you’re not studying
00:15:40 Brian Meshkin
50% of the material, you’re probably going to fail the exam.
00:15:43 Brian Meshkin
And that’s what’s happening, sadly, every day.
00:15:45 Will Mountford
We’ve mentioned that it is part of the current opioid crisis, that it exists through prescribed management of treatment of pain, but also that there is then the unprescribed, not through the doctor’s office.
00:15:56 Brian Meshkin
They are, yeah.
00:15:57 Brian Meshkin
Sadly, one of the unintended consequences anytime there’s a government policy, by restricting physicians who could prescribe and ethically oversee pain patients on their prescription opioids, now most of your
00:16:10 Brian Meshkin
for opioid overdose deaths are people who are going to the streets.
00:16:14 Brian Meshkin
You’ve had this really sad thing emerge, according again to the National Institutes of Drug Abuse and Harvard Medical School, suicides in the United States are at an all-time record high, and 10% of those record high suicides are pain patients who are killing themselves because they can’t get the treatment and the relief of pain that they need, which has been directly caused by government policy, which is tragic.
00:16:34 Brian Meshkin
And then at the same time, for the pain patients that don’t have that impulsivity to kill themselves but are miserable, they
00:16:40 Brian Meshkin
can’t get the life-saving medication that they need because the government has said that these compounds that have been around for 7,000 years are all bad.
00:16:46 Brian Meshkin
Then they end up going to the streets thinking they’re getting some pain medication, but then it gets laced with fentanyl, which nobody really wants.
00:16:54 Brian Meshkin
Then they have these awful reactions.
00:16:57 Brian Meshkin
If you speak with anyone who has had that experience beforehand, the people that become addicted to fentanyl aren’t becoming addicted because of like the buzz that you would have if you’re an alcoholic or a smoker or an opioid abuser or heroin or
00:17:10 Brian Meshkin
cocaine or any of this type of thing.
00:17:11 Brian Meshkin
It’s very, very different.
00:17:12 Brian Meshkin
They’re taking more of it to prevent this awful withdrawal that happens.
00:17:17 Brian Meshkin
So they’re almost like committing suicide intentionally to stop the misery of the withdrawal.
00:17:23 Brian Meshkin
It’s really, really sadistic and awful, which is why some of the policymakers refer to it as a chemical weapon coming across the border.
00:17:29 Brian Meshkin
It’s really, really quite awful, horribly tragic.
00:17:32 Brian Meshkin
And so to that end,
00:17:33 Brian Meshkin
these poor people that can’t get the relief they need from their doctor anymore because the doctor’s scared to death to prescribe these medications and now the government’s cracking down on even the alternatives like neurostimulation and those type of things for these pain patients so they can’t get that either.
00:17:47 Brian Meshkin
They end up going to the streets trying to get some type of relief from illicit substances because their, you know, prescriptions are sold on the street, you’re not picking them up at the pharmacy and it just is an awful lose-lose situation.
00:17:59 Will Mountford
And it’s worth noting the social dimensions both in space and time that this is happening that
00:18:04 Will Mountford
In England as well, we are in a cost of living crisis that people are unable to see a doctor because the health system is straining under high demands with an ageing population, rising disability rates, huge swaths of population left disabled and in pain due to the pandemic because of the kind of the long lasting long covid effects.
00:18:22 Will Mountford
I know those affected some people in my life personally that they are now just in chronic pain.
00:18:27 Will Mountford
So having the aspect of not being able to get the medication, not being able to support a health system that provides that medication, not being able to look after the people who have no alternative because they are going to be old and in pain, leaves us in something of a perfect storm of hurt again.
00:18:45 Will Mountford
The harm is undeniable, but we must move to harm reduction.
00:18:49 Will Mountford
How can we reduce that harm for society, for people, and eventually funnel down to the individual level?
00:18:54 Will Mountford
Or maybe it’s best to start from the individual level and work our way back up to society.
00:18:58 Will Mountford
How can we reduce pain in a person by understanding their DNA level?
00:19:04 Will Mountford
Atomic level identification of what makes a person and how then that builds out to a population level policy.
00:19:10 Brian Meshkin
I’m so grateful you brought that up well, because we think of the way these medications or treatments or anything are studied.
00:19:17 Brian Meshkin
They’re statistically powered to hopefully predict the population.
00:19:21 Brian Meshkin
They’re constantly looking for the mean or the average.
00:19:24 Brian Meshkin
I don’t know about you, but I’ve never met an average person.
00:19:27 Brian Meshkin
I’ve never met an average family.
00:19:28 Brian Meshkin
I’ve never met a normal person, a normal family.
00:19:32 Brian Meshkin
I think that everybody is pretty darn unique.
00:19:35 Brian Meshkin
As a dad of three kids biologically and two bonus kids through my second marriage, I mean, they’re all unique.
00:19:41 Brian Meshkin
And they all come to this earth, this life, with these unique tendencies and personalities and all this type of stuff.
00:19:47 Brian Meshkin
And they can be raised in the exact same environment.
00:19:49 Brian Meshkin
It’s fascinating to me.
00:19:50 Brian Meshkin
And so to that end, I agree with you that I think it has to start at the individual level.
00:19:55 Brian Meshkin
And I think every clinician knows that because doctors and nurse practitioners and others, they’ve been practicing personalized medicine, trying to figure out what’s working for that patient right in front
00:20:05 Brian Meshkin
of them forever.
00:20:06 Brian Meshkin
The system doesn’t do that, but I really believe that clinicians in their heart really try to do that.
00:20:12 Brian Meshkin
And so to that end, with Proove, what we are able to do is…
00:20:16 Brian Meshkin
with a simple oral specimen, simple swab of the mouth or spit, we are able to collect genetic information and then with some information that’s pulled from the medical record and or pulled from interviewing the patient, we’re able to combine the genetic factors with the non-genetic factors to be able to objectively assess how that one person in front of you feels pain, what could be driving their sensations of pain, is it the genetics, is it stress, because stress plays a huge
00:20:46 Brian Meshkin
role in this?
00:20:47 Brian Meshkin
Is it some other factors that go into it that can then guide therapy, can then predict how long someone’s going to take to recover from a whiplash or from a surgery or from an athletic injury, workplace injury?
00:20:58 Brian Meshkin
And then we can figure out those risk factors like, okay, can I safely give this person opioids?
00:21:03 Brian Meshkin
Because they’re very inexpensive and they’ve been around for a long time.
00:21:06 Brian Meshkin
Or can I only give them safely for a short period of time?
00:21:09 Brian Meshkin
And then I have to look at something else, you know, rational decision-making.
00:21:12 Brian Meshkin
And then instead of let’s try this out and see if it works, this empiric trial
00:21:16 Brian Meshkin
trial and error guesswork that’s done to figure out what to prescribe.
00:21:20 Brian Meshkin
We can also give insights based upon the genetics and non-genetic factors as to what would be the best treatments to give for those patients.
00:21:29 Brian Meshkin
And understand that when I say that, I’m not just saying that theoretically like some startup.
00:21:34 Brian Meshkin
No, we have done this in hundreds of thousands of patients.
00:21:38 Brian Meshkin
We have published this in peer-reviewed journals with accuracy studies of thousands of patients.
00:21:43 Brian Meshkin
outcome studies of tens of thousands of patients to be able to show that not only can you predict and objectively assess this, but when a clinician uses the information, the pain gets reduced by 50% within 30 days and persists for months and we can prevent any opioid use disorder from emerging.
00:22:02 Brian Meshkin
And I just want you to understand that it’s not something that’s in a theory or an experimental design or a business plan that we’re trying to raise money off of in some novel startup.
00:22:10 Brian Meshkin
No, we’ve been there, done this, we’ve shown the
00:22:13 Brian Meshkin
curve bend with the CDC.
00:22:15 Brian Meshkin
We’ve published the results.
00:22:16 Brian Meshkin
We’ve tested hundreds of thousands of patients.
00:22:18 Brian Meshkin
And maybe it’s because of that good we poked some bear and that’s why they came after us.
00:22:22 Brian Meshkin
But not only does the name of the company Proove, but we’ve also proven it.
00:22:31 Will Mountford
Could dig into some of the science there, because when I think of the genetic signs and signals that some of our audience might understand, they could think of heritability as you get your hair color, eye color.
00:22:42 Will Mountford
Those are things that you can find in the DNA.
00:22:44 Will Mountford
We know the gene for blue eyes, brown hair.
00:22:47 Will Mountford
Where in the genome is pain?
00:22:49 Brian Meshkin
In all of these things, they’re in multiple places.
00:22:52 Brian Meshkin
So let me just take one example.
00:22:54 Brian Meshkin
You talked about
00:22:55 Brian Meshkin
having that stimulus of pain beforehand.
00:22:57 Brian Meshkin
There’s different types of stimulus for pain.
00:22:59 Brian Meshkin
Think about like when our kids were young and they touched a hot pan.
00:23:02 Brian Meshkin
That finger touched the hot pan accidentally.
00:23:05 Brian Meshkin
Those neurons from the peripheral nerves went all the way up their arm in a matter of milliseconds to their spine, all the way up the dorsal ganglia to the brain, said, hello, ouch, dummy, pull your hand off the pan, right?
00:23:17 Brian Meshkin
So heat could be a sensation of it.
00:23:20 Brian Meshkin
Cold can be a sensation of it.
00:23:22 Brian Meshkin
Pressure can be a sensation of it.
00:23:23 Brian Meshkin
There’s different types of pains
00:23:25 Brian Meshkin
stimuli that happen.
00:23:27 Brian Meshkin
But like you said, pain in and of itself is the body’s natural warning sign.
00:23:32 Brian Meshkin
Like if you think of like Eastern medicine, like traditional Chinese medicine, pain isn’t bad per se in the sense that it’s a signal for survivability to say, hey, this is dangerous, don’t do it.
00:23:42 Brian Meshkin
And so that signal of pain coming to you and telling you that creates A body’s survival instinct, creates a stress response because it’s a ding, ding, ding, ding, ding warning.
00:23:55 Brian Meshkin
One of those happens amongst, as you mentioned, neurotransmitters.
00:23:59 Brian Meshkin
And so as the neurotransmitters are crossing the synaptic cleft in the brain, because it’s ultimately going to the primordial area of the brain, the hypothalamus, the amygdala, kind of the area of the brain where the spinal cord comes right into, not where you think, but where you feel.
00:24:15 Brian Meshkin
You feel pain, you feel lust, you feel love, you feel hunger, you feel anger.
00:24:20 Brian Meshkin
Not the prefrontal cortex where your thinking or memory is, but this primordial area of the brain.
00:24:25 Brian Meshkin
And that synaptic cleft is these neurotransmitters are crossing there and giving the body sensation that’s going to govern thoughts, feelings, muscle impulses, et cetera.
00:24:35 Brian Meshkin
There’s kind of this neurotransmitter that acts as a sheriff.
00:24:38 Brian Meshkin
It’s called catecholamine methyltransferase, or COMT, C-O-M-T.
00:24:42 Brian Meshkin
Catecholamines are released when the body feels stress.
00:24:46 Brian Meshkin
It’s a stress-induced response.
00:24:49 Brian Meshkin
these various different catecholamines.
00:24:50 Brian Meshkin
This particular enzyme is kind of like the sheriff.
00:24:53 Brian Meshkin
If there’s an imbalance in that synaptic cleft, then the sheriff is going to govern things and make sure that everyone’s kind of balanced and there’s law and order, so to speak, as a metaphor.
00:25:04 Brian Meshkin
When that sheriff isn’t present there, can be imbalance because there isn’t any enforcement of the rules that’s happening.
00:25:13 Brian Meshkin
And so if there are genetic predispositions that govern that enzyme activity, kind of the domino
00:25:19 Brian Meshkin
Effect becomes a situation where, if there is an imbalance in the genetics, it creates an imbalance of the enzyme that’s the law and order kind of governing enzyme amongst that stress response when someone then has that noxious stimuli, whatever that is, pressure.
00:25:35 Brian Meshkin
heat, cold, whatever it is that causes that ouch sensation to relay to the brain as those communications are happening across the synaptic cleft, if law and order isn’t present there due to the genetic predisposition, you’re going to have an abnormal or different type of response.
00:25:50 Brian Meshkin
About 11% of the world’s population is genetically predisposed to be a high perceiver of pain.
00:25:57 Brian Meshkin
What does that mean?
00:25:57 Brian Meshkin
It doesn’t mean they’re a wuss.
00:25:59 Brian Meshkin
It doesn’t mean that they’re catastrophizing and blowing it out of proportion.
00:26:03 Brian Meshkin
It doesn’t mean they’re lying to the doctor when they say it’s a 30 on a scale from a 0 to 10 because they’re drug seeking and they want, they’re an addict and want opioids.
00:26:11 Brian Meshkin
No, it just means that genetically they feel pain far more than the average person does.
00:26:17 Brian Meshkin
And so to that end,
00:26:18 Brian Meshkin
Just addressing the pain relief without addressing the imbalance in the brain and how to help them regulate that is going to fail miserably.
00:26:26 Brian Meshkin
They’re going to screw up the clinical trials in pain for different new pain treatments.
00:26:30 Brian Meshkin
It’s not that the pain treatments don’t work.
00:26:32 Brian Meshkin
It’s just they’re part of the population that it works differently.
00:26:34 Brian Meshkin
And that’s why one of the reasons why pain studies are so hard to do for new novel therapeutics and devices and those type of things.
00:26:40 Brian Meshkin
And so it doesn’t mean there’s anything wrong with that person.
00:26:42 Brian Meshkin
It just means that that’s part of their uniqueness.
00:26:44 Brian Meshkin
Part of their beauty is God’s creation.
00:26:46 Brian Meshkin
You treat them differently.
00:26:47 Brian Meshkin
It doesn’t mean they’re broken.
00:26:48 Brian Meshkin
which means that they need to be treated differently.
00:26:50 Brian Meshkin
For the person who has a low perception of pain, these are almost the people that almost like self-select as they’re trained as special operations in the military or Navy SEALs in the United States or those type of things.
00:27:01 Brian Meshkin
These are people that just don’t feel pain as much as the average person does.
00:27:05 Brian Meshkin
Now, that could also be problematic because they could have a broken bone and it ends up getting worse because they don’t go into the doctor because they’re like, hey, I’ll be fine, you know.
00:27:12 Brian Meshkin
So there’s variability in that.
00:27:14 Brian Meshkin
And obviously most of the people are in the middle on the bell curve type situation that have an average perception of pain.
00:27:19 Brian Meshkin
But that genetics can govern that enzyme activity.
00:27:22 Brian Meshkin
This is one of the mechanisms of action of how we feel pain, and by virtue of that, makes us unique and different.
00:27:28 Will Mountford
It touches on some of the biology behind improved genomics, but then another part that you’ve already mentioned is the algorithm, the mechanical machine language sorting of all of that information.
00:27:38 Will Mountford
How does that come to bear on pain sorting and how that works then for clinicians looking at patients?
00:27:45 Brian Meshkin
So let’s take that exact same situation.
00:27:46 Brian Meshkin
So we have that situation where let’s say someone is an average perceiver of pain.
00:27:50 Brian Meshkin
The COMT sheriff is operating the way the average should be done, most of the population, and that’s happening.
00:27:57 Brian Meshkin
Well, we also published a study.
00:27:59 Brian Meshkin
There is a particular validated assessment of stress, but specifically perceived stress.
00:28:05 Brian Meshkin
It’s called the perceived stress scale.
00:28:08 Brian Meshkin
And when we assess the perceived stress scale, and we also assess gender in this particular study, we found
00:28:14 Brian Meshkin
that if somebody, by virtue of just life happening, we all signed up for this mortal journey and life’s hard.
00:28:21 Brian Meshkin
Crap happens.
00:28:22 Brian Meshkin
People are dealing with various different health issues, financial issues, family issues, you name it.
00:28:29 Brian Meshkin
We’re all dealing with various different crap hitting the fan.
00:28:32 Brian Meshkin
And that’s just part of our mortal journey.
00:28:33 Brian Meshkin
That’s all part of the weightlifting that we’re doing to become stronger.
00:28:37 Brian Meshkin
It can be hard.
00:28:37 Brian Meshkin
It can be real hard.
00:28:39 Brian Meshkin
And if we feel that we’re under a high level of stress, where perceived stress is very high, let’s say we’re just like it’s happening in spades, right?
00:28:48 Brian Meshkin
It’s like a perfect storm our life is facing.
00:28:51 Brian Meshkin
And we’re just like, man, I am really, really stressed out.
00:28:54 Brian Meshkin
That perceived stress scale being high actually manifested the same way as someone who was genetically
00:29:02 Brian Meshkin
predisposed to high perception of pain.
00:29:04 Brian Meshkin
So what does that mean?
00:29:05 Brian Meshkin
It means that someone could be genetically average perception of pain.
00:29:09 Brian Meshkin
So on a scale of 0 to 10, you know, that crazy numerical scale, they say it’s a 5.
00:29:13 Brian Meshkin
It’s probably similar to the way most people would rate a 5.
00:29:16 Brian Meshkin
But because of what’s going on in their life, they feel it more than the average person.
00:29:21 Brian Meshkin
So they’re reporting it as a 10.
00:29:23 Brian Meshkin
Though it was the same injury maybe that five years ago before the crap hit the fan was a 5.
00:29:28 Brian Meshkin
Now it’s a 10, not because the injury is any worse.
00:29:31 Brian Meshkin
Not because something you’re going to see under an x-ray or an MRI looks more severe, requiring surgery, none of those things, but purely because their perception of the stress in their life has gone up.
00:29:43 Brian Meshkin
So obviously, knowing that what we call phenotypic data in combination with the genetic data would certainly guide the clinician’s treatment differently than not knowing it.
00:29:55 Brian Meshkin
Because you’re thinking, oh, gosh, the injury must have gotten worse.
00:29:57 Brian Meshkin
Let’s go order an MRI, an x-ray, send them to a surgeon, et cetera.
00:30:01 Brian Meshkin
No, no,
00:30:01 Brian Meshkin
No, no, no.
00:30:02 Brian Meshkin
That has nothing to do with it.
00:30:03 Brian Meshkin
Don’t waste the money.
00:30:04 Brian Meshkin
Don’t waste the time.
00:30:05 Brian Meshkin
Don’t make the stress worse on the person thinking, oh my gosh, and now I’m going to need surgery.
00:30:09 Brian Meshkin
I’m going to be missing work, et cetera, et cetera.
00:30:11 Brian Meshkin
That’s the irrational current status quo.
00:30:15 Brian Meshkin
By using the proof technology, you would know, okay, this is not due to the genetics in this particular example that we talked about.
00:30:20 Brian Meshkin
It’s actually due to their perceived stress.
00:30:22 Brian Meshkin
So what can I do to help them reduce their stress?
00:30:25 Brian Meshkin
Therapy, massage, whatever it may be to help them.
00:30:29 Brian Meshkin
Maybe it’s what the consultants call social
00:30:31 Brian Meshkin
determinants of health.
00:30:32 Brian Meshkin
Let’s help them with their financial issues, their housing issues, their family issues, the life stuff that gets in the way of health.
00:30:39 Brian Meshkin
Let’s address that.
00:30:41 Brian Meshkin
And guess what?
00:30:41 Brian Meshkin
Their pain then goes down.
00:30:43 Brian Meshkin
So it’s a very human approach.
00:30:45 Brian Meshkin
One of the things that I feel so passionate about in dealing with both physical and emotional suffering, it’s not really a healthcare issue.
00:30:54 Brian Meshkin
It’s just life.
00:30:55 Brian Meshkin
They’re things that we’re all going to go through.
00:30:57 Brian Meshkin
We’re all going to experience pain.
00:30:58 Brian Meshkin
We’re all going to experience emotional suffering in our lives.
00:31:01 Brian Meshkin
They are the
00:31:01 Brian Meshkin
the two health conditions that all of us are going to deal with at some point in time.
00:31:05 Brian Meshkin
And so if we can help that better, we’re not just dealing with a health issue, we’re dealing with improving people’s lives.
00:31:11 Brian Meshkin
And I think that’s really significant.
00:31:13 Will Mountford
I like the idea of not just fixing someone’s broken bone, but fixing the hurt in their life around that.
00:31:19 Will Mountford
Again, that broader definition of harm, to get into harm reduction.
00:31:27 Will Mountford
To follow the line of the Proove perception test, then we also get on to that when someone has been prescribed the drugs and they take the drugs, what those drugs then do determines how they feel their response.
00:31:38 Will Mountford
So understanding drug metabolism, that’s got to be a huge part of how someone then feels that analgesia, feels the pain relief and how they then proceed in their life to either seek further pain relief or to go about their life without that harm hanging over them.
00:31:52 Will Mountford
What does Proove say about metabolism?
00:31:54 Brian Meshkin
Once we kind of objectively assess pain and objectively kind of assess the opioid risk, which I’m happy to talk with you more about as well and kind of what goes into that algorithm, then you’re right.
00:32:03 Brian Meshkin
Metabolism plays a huge role.
00:32:04 Brian Meshkin
I mean, we were just sitting down and having lunch together right now, and we were eating food.
00:32:08 Brian Meshkin
We were putting something into our mouth to be digested.
00:32:11 Brian Meshkin
We may metabolize that food differently.
00:32:13 Brian Meshkin
I personally have Crohn’s disease, and so I have to be careful with what I eat, and I manage it with supplements and diet.
00:32:19 Brian Meshkin
I don’t have to take any medication for it.
00:32:20 Brian Meshkin
I’ve been able to keep it in remission for almost 20 years now, which is great.
00:32:24 Brian Meshkin
So I hacked it, so to speak, by figuring out that personalization for me.
00:32:28 Brian Meshkin
But we all metabolize things differently.
00:32:31 Brian Meshkin
Now, I love beef.
00:32:31 Brian Meshkin
You may love beef, but I can only really do beef like once a week at best because otherwise it tears my system up.
00:32:37 Brian Meshkin
Well, when we put a pill in our mouth, it’s going through the exact same digestive tract that our body’s going, that our food is going through.
00:32:45 Brian Meshkin
And it ultimately is getting metabolized.
00:32:48 Brian Meshkin
Some may actually start in our mouth and then it gets into our stomach and then into the nether parts of our digestive tract.
00:32:54 Brian Meshkin
medications, if you read like the package inserts of those medications, it talks about basically the kinetics or how those medications move or metabolize in the body.
00:33:04 Brian Meshkin
I’m one for metaphors.
00:33:05 Brian Meshkin
You probably picked up on that in our discussion, but I use the metaphor of kind of exit ramps off the freeway.
00:33:10 Brian Meshkin
You have certain medications that are designed to go home where their intended destination is at certain locations, like one may be exit 2D6 on
00:33:19 Brian Meshkin
off the freeway.
00:33:20 Brian Meshkin
One may be exit 2C9, another one may be 2C19.
00:33:24 Brian Meshkin
There are these various different enzymes, kind of getting back to that idea we talked about COMT beforehand.
00:33:29 Brian Meshkin
There are these metabolizing enzymes that are the little exit ramps that basically are produced out of the liver that take the medication and ultimately convert it into its intended result and have its effect.
00:33:40 Brian Meshkin
Well, there are genetics that play a role in the activity of those enzymes as well.
00:33:46 Brian Meshkin
And that can affect heart medications, it can affect diabetes medications,
00:33:49 Brian Meshkin
It can affect antibiotics and pain medications, antidepressants, a host of different things.
00:33:54 Brian Meshkin
Most of these medications are hepatically or metabolized in the liver, some are in the kidneys.
00:33:59 Brian Meshkin
There’s some enzymes and genes around that, but the genetics plays a role there.
00:34:04 Brian Meshkin
And which medications people are taking, foods they’re eating, et cetera, also.
00:34:10 Brian Meshkin
impact those drug metabolizing enzyme activities.
00:34:13 Brian Meshkin
So by combining the genetics with the other things that govern, call it whether the exit ramp off the freeway has both lanes open, has some construction, and one lane is closed, or it’s completely blocked and you got to take a detour, is going to affect the traffic pattern coming off of the freeway.
00:34:34 Brian Meshkin
And so a drug-drug interaction, we probably all have heard of, is basically two vehicles competing
00:34:40 Brian Meshkin
for the same exit ramp off the freeway and expressing a little bit of road rage.
00:34:44 Brian Meshkin
Maybe not being polite and saying, go ahead and hop in front of me kind of thing, but both kind of competing and saying, darn it, I’m getting there first.
00:34:50 Brian Meshkin
And they collide with each other.
00:34:52 Brian Meshkin
That’s A drug-drug interaction.
00:34:53 Brian Meshkin
It’s basically road rage between 2 medications.
00:34:56 Brian Meshkin
That road rage becomes worse when one of the two lanes on the exit ramp are blocked by construction, because now instead of two people competing for two lanes, you’ve got two people competing for one.
00:35:06 Brian Meshkin
And it’s definitely substantially worse and could be deadly.
00:35:10 Brian Meshkin
If the exit ramp is closed, then you’ve got these two ticked off drivers that are trying to figure out how they’re going to do their detour.
00:35:15 Brian Meshkin
So metaphorically speaking, that’s what happens with drug-drug interactions.
00:35:21 Brian Meshkin
And what these enzymes do is the exit ramp off the freeway.
00:35:25 Brian Meshkin
And the genetics can influence the activity of those enzymes.
00:35:29 Brian Meshkin
And the medications you’re taking can actually influence the activity of those enzymes, as well as the foods you eat and those type of things.
00:35:34 Brian Meshkin
So with Proove drug metabolism, which is another one of our algorithms, we are able to assess that.
00:35:40 Brian Meshkin
And what you oftentimes happen with pain patients, and it’s probably because it’s the nation’s most prevalent and most expensive health condition.
00:35:46 Brian Meshkin
It’s the number one reason why people go to the doctor, pain.
00:35:49 Brian Meshkin
It’s the number one medication prescribed by primary care physicians in the United States, is pain patients who are taking pain meds generally aren’t just taking pain medications.
00:35:59 Brian Meshkin
For example, in our VA system in the United States that takes care of our veteran heroes that have gone all around the world to try to help various different countries, these veterans on average are on like 20 medications.
00:36:10 Brian Meshkin
and over 60% of them have chronic pain.
00:36:12 Brian Meshkin
Those 20 medications have never been studied in a clinical study with all 20 medications at the same time.
00:36:19 Brian Meshkin
Didn’t exist.
00:36:20 Brian Meshkin
They were all studied one by one, so that didn’t look anything like reality.
00:36:23 Brian Meshkin
And now probably some of those medications are being prescribed for the side effects of other medications, and some of the doctors don’t even know that the patient’s taking all these medications.
00:36:31 Brian Meshkin
That’s what’s presented in front of that clinician today.
00:36:35 Brian Meshkin
There’s no studies to suggest how all these 20 medications work together at the same time.
00:36:40 Brian Meshkin
Imagine like baking a cookie with, all these ingredients in the recipe and no one’s ever tried it before.
00:36:45 Brian Meshkin
Kind of crazy.
00:36:46 Brian Meshkin
And so to that end, we assess that and then can say, okay, this will work, this won’t work, don’t do this, don’t do that.
00:36:54 Brian Meshkin
And based upon their perception of pain, so that objective assessment of pain.
00:36:57 Brian Meshkin
And then whether opioids are really something that can be used or used short-term or can be used long-term, here’s what you need to look at.
00:37:04 Brian Meshkin
And obviously, we don’t just give them the insights on pain, but we give them the insights on all the medications because the patient in front of them is not just a pain patient.
00:37:11 Brian Meshkin
They may be a pain patient with diabetes and heart disease and can’t sleep.
00:37:14 Brian Meshkin
And so they’re taking a bunch of different medications.
00:37:16 Brian Meshkin
So we give them all those insights.
00:37:17 Brian Meshkin
And by doing that, again, we’ve proven in published clinical studies and outcomes about 13,000 patients across hundreds of clinics in the United States that it works.
00:37:26 Will Mountford
I suppose the fulcrum of the points between pain perception and drug metabolism is the risk of knowing or being able to at least forecast the risk of how we are going to treat this patient, how we’re going to match their metabolism, that tipping point between what can be healthy versus what’s ineffective, what’s healthy versus too much, and then all the ways that things can go wrong for the myriad different reasons.
00:37:51 Will Mountford
How can we put a number in a report given to clinicians, given to patients?
00:37:55 Will Mountford
How can you put a percentage chance to risk with all of that kind of hanging in the balance?
00:38:01 Brian Meshkin
In regards to opioids, and this is obviously a very politically charged thing because you have over 100,000 people in the United States dying from opioid overdose deaths every year.
00:38:09 Brian Meshkin
It’s the nation’s leading cause of preventable death.
00:38:11 Brian Meshkin
And then you also have chronic pain being the nation’s most part of the most expensive health condition.
00:38:15 Brian Meshkin
Opioids in and of themselves, again, have been around for a very, very long time.
00:38:18 Brian Meshkin
They can be safely given to patients.
00:38:20 Brian Meshkin
You know, opioids are not bad.
00:38:22 Brian Meshkin
It’s kind of like a gun, right?
00:38:24 Brian Meshkin
You know, a gun in the hand of a soldier or someone trying to protect themselves or those type of things, police officer, whatever it may be.
00:38:30 Brian Meshkin
That’s a
00:38:31 Brian Meshkin
good thing.
00:38:31 Brian Meshkin
A gun in the hands of a criminal trying to hurt somebody, bad thing.
00:38:35 Brian Meshkin
And so we want to make sure that opioids are in the hands of people that will help and not in the hands of people that will hurt.
00:38:43 Brian Meshkin
And so to that end, there’s a genetic component to it, because that’s about 50% of the factors.
00:38:47 Brian Meshkin
But it’s not like the examples you used beforehand, you know, blue eyes, red hair, or some health conditions like Huntington’s disease or those type of things, all because you have the genetic predisposition to abusing opioids or becoming an alcoholic or whatever.
00:39:01 Brian Meshkin
whatever the situation may be, there’s going to be some demographic, behavioral, environmental factors that are going to play a role in there.
00:39:09 Brian Meshkin
You know, I’m a member of the Church of Jesus Christ of Latter-day Saints.
00:39:12 Brian Meshkin
I don’t drink alcohol.
00:39:13 Brian Meshkin
I don’t smoke tobacco.
00:39:15 Brian Meshkin
I don’t do illegal drugs.
00:39:16 Brian Meshkin
I don’t do those things.
00:39:17 Brian Meshkin
And so there wouldn’t be that history, let’s say, in my life.
00:39:22 Brian Meshkin
Oh, this person’s been an alcoholic beforehand, or they’ve abused illegal drugs.
00:39:26 Brian Meshkin
They peed in the urine cup, and I saw something in there that was a bothersome issue.
00:39:30 Brian Meshkin
I’m worried about
00:39:31 Brian Meshkin
them.
00:39:31 Brian Meshkin
No, you wouldn’t see that with me because there hasn’t been that behavioral component.
00:39:35 Brian Meshkin
But I could, fortunately I don’t, but I could have the genetic predisposition to opioids.
00:39:41 Brian Meshkin
I have plenty of friends who are also members of my religious faith and the
00:39:46 Brian Meshkin
They got hurt at work, got hurt in an athletic injury, and they got prescribed opioids because the doctor gave it to them and they trust their doctor and these are approved by the FDA.
00:39:56 Brian Meshkin
And several years later, they’re not only abusing opioids, but now they’re into heroin and all these other things and spiraled out of control.
00:40:03 Brian Meshkin
We found, we built the world’s largest clinical genetic biobank in the field of chronic pain.
00:40:08 Brian Meshkin
So it’s not an end-all be-all, but we were tracking about 153,000 patients where we had the genetic information.
00:40:13 Brian Meshkin
We were tracking them monthly.
00:40:15 Brian Meshkin
And we
00:40:16 Brian Meshkin
We found that to people that are actually at risk, high risk for misusing opioids, there’s some people that are at moderate risk, but they can be monitored.
00:40:24 Brian Meshkin
But those that are at high risk is really a small percentage of the population, generally between 10 and 14%.
00:40:30 Brian Meshkin
So it’s, call it one out of every 10 people.
00:40:33 Brian Meshkin
Unfortunately, public policy has just basically said, okay, we’re going to put an arbitrary limit on dosing and we’re going to limit the prescribing of opioids and we’re going to make doctors scared to freaking death to prescribe them.
00:40:45 Brian Meshkin
And so many of these patients got forced to taper down onto lower doses.
00:40:49 Brian Meshkin
They may have had metabolic issues like we talked about beforehand, et cetera, et cetera.
00:40:52 Brian Meshkin
And so if you can look at the genetics, the hereditary component, and then we also look at demographics like age and depression.
00:40:59 Brian Meshkin
What was really interesting to me is the algorithm evolved.
00:41:02 Brian Meshkin
We were doing artificial intelligence or machine learning, those type of things, long before the terms became coined.
00:41:08 Brian Meshkin
And we were having the software kind of analyze the data over and over and over and over again, because we weren’t relying upon one study.
00:41:14 Brian Meshkin
We were just looking
00:41:15 Brian Meshkin
reality.
00:41:15 Brian Meshkin
The same way, you know, Apple probably looks at my iOS every day on my iPhone and figuring out what’s Brian doing.
00:41:21 Brian Meshkin
We were tracking people and finding out what was happening in reality.
00:41:24 Brian Meshkin
And what was interesting to me, it wasn’t something that I came up with, it just the data showed it, was that one of the most significant factors contributing to someone who would misuse opioids became a diagnosis of depression.
00:41:38 Brian Meshkin
And that was really, really interesting.
00:41:40 Brian Meshkin
In fact, out of all the variables, and there’s lots of variables that go into that equation, to
00:41:45 Brian Meshkin
then classify someone with a score like you talked about low, moderate risk, or high risk.
00:41:49 Brian Meshkin
If you look at the statistics, the R-squared is the correlation coefficients, if you will get into the mathematics.
00:41:54 Brian Meshkin
One of the ones that has the largest contributing factor is the PHQ, which is a depression questionnaire, which gets into issues around feelings of self-worth, suicide, all these various different things that are asked.
00:42:07 Brian Meshkin
If somebody has
00:42:09 Brian Meshkin
has been feeling depressed and has those feelings.
00:42:12 Brian Meshkin
Separate from the pain, separate from the genetics, but again, another phenotype puts them at risk for misusing opioids.
00:42:18 Brian Meshkin
And that becomes scary because if someone’s a chronic pain patient, they’re sore all the time, they may not be sleeping well, probably a little grumpy, rightfully so, may not be able to do the fun things they’ve been able to do in the past.
00:42:30 Brian Meshkin
Maybe there’s some tension in their personal relationships because they’re grumpy now.
00:42:33 Brian Meshkin
A host of different things.
00:42:35 Brian Meshkin
Chances are they could be feeling depression.
00:42:36 Brian Meshkin
So it’s like a chicken or egg type situation, which is why when you look at the population data as we zoom out from the individual, there’s about a 60-some percent overlap in mental health issues with pain.
00:42:48 Brian Meshkin
That is a risk factor for someone developing opioid use disorder.
00:42:52 Brian Meshkin
And so the ability, as we talked about, to address some of those life issues and helping people and loving people and supporting people as they’re going through these things is so important to be able to address these concerns.
00:43:04 Brian Meshkin
And so the Proove analysis is able to bring together those life things with the genetic things to really present a clear picture to the clinician who’s trying to help this patient.
00:43:13 Will Mountford
Much the umbrella concept of harm and hurt through not just immediate pain, but a hurt life experience.
00:43:27 Will Mountford
To come back to how you addressed your own experience of pain and hurting and healing and to keep things in the present tense, what is the present tense of Proove at the moment?
00:43:35 Will Mountford
You’ve mentioned all of the trials, the thousands of patients, high percent accuracy, but where is Proove today?
00:43:41 Will Mountford
Who has it today?
00:43:42 Will Mountford
And maybe then we can look a little bit into the future tense of what comes next.
00:43:46 Brian Meshkin
We are just relaunching it now.
00:43:49 Brian Meshkin
And so the funds that I had to start it the first time, obviously all got destroyed.
00:43:55 Brian Meshkin
I put my entire life savings into starting the business.
00:43:57 Brian Meshkin
I had funded it all myself.
00:43:58 Brian Meshkin
I remember my kids’ ages, you know, through all those periods and all the sacrifice that went into getting it where it was.
00:44:04 Brian Meshkin
And then obviously in a matter of eight months, it got destroyed.
00:44:06 Brian Meshkin
And as I mentioned, I went through that Job-like time and then had to take on the government and unfortunately a very acrimonious divorce.
00:44:14 Brian Meshkin
So there was a lot of bad things that happened financially.
00:44:16 Brian Meshkin
So I wasn’t
00:44:16 Brian Meshkin
in any situation now to fund the startup of it the way I was beforehand.
00:44:21 Brian Meshkin
But fortunately with God’s blessings, been able to get some funds together and those type of things to get at least the first three tests up and revalidated.
00:44:30 Brian Meshkin
We have 32 different profiles, but like the three we first talked about, the Proove pain perception, Proove opioid risk, Proove drug metabolism, we’ve revalidated those in a new laboratory that we own, got the equipment, and obviously we have all the records, all the published data, and now we’re gearing up to start commercializing it.
00:44:46 Brian Meshkin
And we
00:44:46 Brian Meshkin
have a lot of interest from the Department of Defense and the Veterans Administration, from former clients, et cetera, that are really, really interested because ironically, even though our mission was halted for eight years,
00:45:00 Brian Meshkin
No one filled the gap.
00:45:01 Brian Meshkin
No one was able to address the issue.
00:45:03 Brian Meshkin
And so we’re going to be able to come back and do the good things we were doing beforehand at a greater scale, get this to be the standard of care as soon as possible, start bending that curve again, saving lives, helping patients.
00:45:16 Brian Meshkin
And we’ve started re-amassing, getting the band back together of some of our former employees that are open to coming back in.
00:45:23 Brian Meshkin
They haven’t moved on to another company and they’re happy with their jobs where they are now, bringing in some new people who have a lot of passion around what we’re doing.
00:45:30 Brian Meshkin
We’re hopeful about what the future holds.
00:45:32 Brian Meshkin
And so in a matter of a couple months, this is going to be available nationwide again.
00:45:38 Brian Meshkin
And sadly, because some of the opioid manufacturers in the United States were bankrupted and then took their things overseas, the opioid overdose crisis has become more than a problem in the United States.
00:45:50 Brian Meshkin
It’s a problem in Canada.
00:45:51 Brian Meshkin
It’s a problem in England.
00:45:52 Brian Meshkin
It’s a problem in India.
00:45:54 Brian Meshkin
It’s a problem in various different parts of the world.
00:45:56 Brian Meshkin
And so what we didn’t do the first time around, we’re going to have to do this time to save
00:46:00 Brian Meshkin
save the lives that we need to save.
00:46:01 Brian Meshkin
And now we’re going to have to put together partnerships with people internationally to make this available internationally, too, because sadly, the issue has become a human problem globally.
00:46:09 Brian Meshkin
As you mentioned, in COVID, they kind of united us globally and all having to deal with the COVID-19 pandemic.
00:46:15 Brian Meshkin
A lot of people have an autonomic nervous system dysfunction from the vagus nerve coming out of the long covid situation or dealing with chronic pain and other ails that they didn’t have beforehand.
00:46:25 Brian Meshkin
And so there are a lot of people we need to help.
00:46:28 Brian Meshkin
And obviously, I learned at a young age
00:46:30 Brian Meshkin
And I’ve learned throughout my life, you don’t really do anything of any significance by yourself.
00:46:33 Brian Meshkin
You do it with a group of people.
00:46:35 Brian Meshkin
And so we’ll be looking for partners internationally and others that are motivated with the same type of intentions and their heart in the right place to do good.
00:46:43 Brian Meshkin
So it’ll be interesting to see what version 2.0 holds.
00:46:46 Will Mountford
All of the people who have listened to this and have been listening through to hear about your journey and Proove’s journey, and now they’ve got to the end, and they’ve maybe a little taken aback by all of it, but also this will help the people who always skip to the end of the podcast, they can just find out what people have actually been talking about.
00:47:00 Will Mountford
about for the past hour.
00:47:01 Will Mountford
If you were to think about all that we’ve talked about today, for a clinician, for a patient, for a policy maker, the levels of someone who can really make some changes on a population level, people are going to make changes on a town level, people are going to make changes in their own life.
00:47:16 Will Mountford
What should people take away at those three different levels to know about pain, genomics, and then what Proove does to unite all of these ideas?
00:47:24 Brian Meshkin
Wow, I thought I’d been asked every question over the years, but I’ve never been asked that one.
00:47:28 Brian Meshkin
That’s a great question, Will.
00:47:29 Brian Meshkin
I appreciate the way you formulated that.
00:47:31 Brian Meshkin
I would say that like most things in life, each individual is a unique person.
00:47:38 Brian Meshkin
And as such, how they feel pain, what’s causing their pain, and what will help them overcome their pain is individual.
00:47:46 Brian Meshkin
And so the individual needs to be assessed.
00:47:49 Brian Meshkin
one-size-fits-all doesn’t work in a lot of things.
00:47:53 Brian Meshkin
Broad generalizations tend to get us into trouble.
00:47:56 Brian Meshkin
And so we need a healthcare system.
00:47:59 Brian Meshkin
that it treats that individual patient, that helps the communities that could be affected by this, and ultimately at the national level, especially in systems like, say, Medicare Part B in the United States, the National Health Service in the UK, where there is a burden on the taxpayers, we’re all in this together, to come up with ways that work for the individual.
00:48:19 Brian Meshkin
And if it works for the individual, it works for their families.
00:48:22 Brian Meshkin
And if it works for the individuals in a town or community, then it works for that town and community.
00:48:26 Brian Meshkin
And so taking, I’ve always been a grassroots
00:48:29 Brian Meshkin
person.
00:48:29 Brian Meshkin
So taking that bottom-up approach, starting with the individual, I’ve always been struck, hearkening back to my religious beliefs on how my Savior Jesus Christ ministered to each individual one person.
00:48:43 Brian Meshkin
And sometimes we refer to that straight and narrow path.
00:48:46 Brian Meshkin
I don’t think it’s narrow because God wants to keep people out.
00:48:50 Brian Meshkin
No, I think He wants everybody in heaven, but I believe it’s narrow because He takes that time with each one of us individually.
00:48:57 Brian Meshkin
I believe that every individual is special.
00:48:59 Brian Meshkin
Every individual is important.
00:49:01 Brian Meshkin
Every person has value.
00:49:03 Brian Meshkin
And if we had a healthcare system that treated people that way rather than as a number, it would be more cost-effective.
00:49:10 Brian Meshkin
It would be more effective in helping that person.
00:49:13 Brian Meshkin
And I think that if we did that at the clinical level with each patient, at the town level, and at the public policy level, we could have a huge, huge impact.
00:49:22 Brian Meshkin
And if we could reduce pain at the individual level and at the national level, and obviously at the global level, we would substantially reduce cost.
00:49:32 Brian Meshkin
I mean, when you think that pain costs us more than cancer, diabetes, and heart disease combined, imagine
00:49:40 Brian Meshkin
the budget savings.
00:49:41 Brian Meshkin
It would happen.
00:49:42 Brian Meshkin
You talked about having constrained resources.
00:49:45 Brian Meshkin
If we could do a better job with pain, and for a couple hundred bucks, you can do the proof testing and save a lot of pain and agony, pun intended.
00:49:54 Brian Meshkin
And so to that end, I think that that’s where it starts.
00:49:57 Brian Meshkin
It starts with recognizing the dignity and the individuality of every single person.
00:50:03 Will Mountford
Do you want to know more about Proove or about you or any of the publications that detail how effective and statistically significant everything is?
00:50:12 Will Mountford
Where would you like to send them for a little bit of the onward journey?
00:50:14 Brian Meshkin
Great.
00:50:14 Brian Meshkin
They can go to the episode description, and we also have a website that we’re in the midst of updating right now, which is just www.proove, but it’s spelled with two O’s: P-R-O-O-V-E.com.
00:50:26 Brian Meshkin
I know that the people who have taken the time from their busy schedules to listen to this have people in their families that are affected by this too.
00:50:33 Brian Meshkin
It’s something that we all deal with.
00:50:35 Brian Meshkin
It’s part of the human experience.
00:50:37 Brian Meshkin
And my hope is in that shared tribulation that can be consecrated for good, that we can kind of come together as a community of people to make a difference and hopefully Proove can contribute to that solution that will help bless the lives of so many.
00:50:52 Will Mountford
Thank you so much for your time, Brian.
00:50:53 Brian Meshkin
Thank you, Will.
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