You have metastatic prostate cancer, and your doctor has said you’re doing all you can do.  How can you be sure?  This is a post that’s very close to my heart, because I have met many men over the years who hear this from their doctors and they just accept it.  Maybe you truly are doing all you can do.  But maybe you aren’t.  With the hope of fighting the spirit of complacency or worse, despair, that can overtake anyone with an illness so easily, I recently interviewed Duke oncologist Andrew Armstrong for the Prostate Cancer Foundation (PCF).  He proved to be a kindred spirit, who wants to encourage men not to give up.

“This is all we can do” is a phrase no cancer patient wants to hear, especially someone with metastatic disease.  Medical oncologist and PCF-funded investigator Andrew Armstrong, M.D., M.Sc., hears those six words a lot – from patients who have come to see him at Duke University’s Cancer Center, a comprehensive cancer and clinical trial center.  The patients are hoping their local doctor was wrong – that this is, in fact, not all that can be done.

And here’s some good news:  Often, there is something more, and the list of options is growing even as we speak.  “The FDA has approved many new therapies for advanced prostate cancer,” says Armstrong.  The challenge, he adds, is in knowing which of these might be helpful for you – and which are likely a waste of your time and money.

Why don’t all of these drugs work for everyone?  Because underneath the umbrella diagnosis of metastatic prostate cancer are many factors that make the response to treatment different in each man.  Understanding whether or not you have some of these factors could not only save you thousands of dollars, but could point you away from treatment that is not going to work, and toward better, more promising options.

Do you need a “liquid biopsy?”  Armstrong and investigators at five centers recently completed the PROPHECY trial, funded by a Movember-PCF Global Challenge Award.  The study’s goal was to use a “liquid biopsy” – a blood test that can detect circulating tumor cells (CTCs) shed by prostate cancer – to evaluate a biomarker called AR-V7 as a predictor of response to androgen receptor-blocking drugs such as abiraterone (Zytiga) and enzalutamide (Xtandi).  AR-V7 is a variant androgen receptor that some men develop over time.  “AR-V7 does not show up when you’re first diagnosed with prostate cancer,” says Armstrong, “and it generally does not show up before you start hormonal therapy.  It only shows up when a patient has developed resistance to commonly used hormonal therapies like leuprolide or degarelix, and more commonly after he has been taking an androgen receptor pathway inhibitor like enzalutamide or abiraterone.”

The results of the PROPHECY study, published in the Journal of Clinical Oncology and updated this past year in JCO-Precision Oncology, showed that AR-V7 is a “negative predictive biomarker” for response and outcomes to abiraterone or enzalutamide.  In other words, if a blood test shows that your cancer cells have detectable AR-V7, these drugs are not likely going to be helpful for you.  There are two blood tests for AR-V7:  one is an mRNA assay developed at, and offered by, Johns Hopkins, and the other is a more widely available CTC protein-based assay made by Epic Sciences.  Both tests are good, says Armstrong.  “It’s common practice,” he explains, “that if a man has been on enzalutamide and his cancer has progressed, to try another hormonal agent such as abiraterone, and vice versa.  But that strategy can lead to cross-resistance,” where neither drug is effective in this patient.  “These drugs are very expensive.”  Abiraterone is now available in a much less expensive generic form, but enzalutamide can cost more than $10,000 – per month!   That’s a lot of money, particularly if it’s not going to help you.

New Strategy:  Shotgun and Sniper Rifle! 

If you have AR-V7, what should you do instead?  Think shotgun – many pellets aimed at the disease – and sniper rifle – a highly focused, precision medicine approach.  “The answer is not to give up, but also not to give therapies that don’t work,” says Armstrong.  “Right now, drugs that are more effective would be chemotherapy: docetaxel and cabazitaxel, and radium-223,” a drug that mimics calcium – and, like calcium, gets absorbed into areas of bone with a lot of cell turnover, particularly areas where bone metastases are forming.”  Treating cancer in the bones not only improves quality of life, but has been shown to increase survival.   Another experimental way to treat areas of metastasis is with stereotactic ablative radiotherapy (SABR, or SBRT), an intense, focused dose of radiation directly to a metastatic site.

Gene-targeted treatment is another option for some men.  “I look at AR-V7 as not the only blood test you’re going to do, but as part of a broader plan to find a therapy that fits the patient,” says Armstrong.  A small percentage of men have microsatellite unstable (MSI-high) prostate cancer – defects in one or more “spell-checker” genes involved in DNA mismatch repair.  This can be identified by tumor genomic sequencing biomarker tests.  “About 5 percent of men have microsatellite unstable prostate cancer, and those patients can do very well on immunotherapy such as pembrolizumab– and may even get complete remission of their cancer!”

Another small percentage of men – those who have a defective BRCA1 or BRCA2 gene – may have an excellent response to a PARP inhibitor drug like olaparib or rucaparib and to off label platinum-based chemotherapy.   “Ongoing trials are exploring a range of combination approaches of both immune therapies and these targeted agents, as well.”

Armstrong is an investigator in clinical trials for still other treatments: newer immunotherapies, targeted molecular agents, newer AR degraders and other inhibitors of hormone signaling, and PSMA-targeted radionuclides, which can detect and attack areas of prostate cancer throughout the body.  “A negative test (such as a blood test finding AR-V7) doesn’t mean you close all doors.  It just means that other doors may open to you, and if those doors are more likely to help, those are the doors you should open.  But the first step is going to see an expert who can open those doors for you.” Look for a Comprehensive Cancer Center or a PCF-VA Center of Excellence (for Veterans).

And don’t forget:  you can help your body fight prostate cancer, as well!  As we’ve discussed previously, exercise can help minimize side effects and maximize the effectiveness of treatment.  The stress hormone, cortisol, plays a role in some forms of prostate cancer, and lowering stress can help slow down cancer’s growth.  Diet can do a lot:  foods that lower inflammation and insulin resistance can also slow cancer’s growth, and new evidence suggests that caloric restriction can decrease metastasis and increase overall survival.

To sum up:  Don’t accept complacency.  “I see it all the time,” says Armstrong, “and I’ve heard stories you wouldn’t believe,” of patients who have been told there is nothing more that can help them.  “Sometimes, if you just do some of these tests, you can find really actionable results.”  There is almost always something else you can do.  There are clinical trials under way and entirely new avenues of treatment, such as PSMA-targeting radionuclides, that offer tremendous promise.

“Andy Armstrong and his team are making tremendous strides towards precision medicine for men with advanced prostate cancer,” says medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of PCF.  “If your doctor doesn’t mention new tests or experimental treatments – or even different uses for existing treatments that might be helpful for you, then it’s up to you to start this conversation.  And even during the pandemic, some clinical trials are still enrolling patients.”

It never hurts to ask.  Don’t give up! 

In addition to the book, I have written much more about prostate cancer on the Prostate Cancer Foundation’s website, The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington




We’ve talked about PSMA-PET before, but now it has gotten FDA approval for use in imaging prostate cancer.  This is just the start: more approvals are expected.  PSMA-targeting is also being used in Europe and Australia, and in clinical trials in the U.S., as a means of treating prostate cancer, not just showing where it’s hiding in the body.  For the Prostate Cancer Foundation (PCF), I recently interviewed Thomas Hope, M.D., part of a team of scientists at UCSF and UCLA whose PCF-funded research led to the FDA approval for PSMA-PET imaging.  The possibilities here are truly exciting:

“If we can see it on PSMA-PET, we can treat it, right?”

 “My PSA is no longer undetectable after surgery, but cancer didn’t show up on a PSMA-PET scan.  Do I still need radiation therapy?”

 “I’m at high risk of cancer recurrence.  A bone scan was negative, but the PSMA-PET scan shows a few spots of cancer outside the prostate.  Do I have metastatic prostate cancer?”

 These are just some of many new questions that men with prostate cancer and their doctors are starting to deal with after recent FDA approval of PSMA-PET, a new kind of scan that can show, for the first time, the needles in the haystack – tiny spots of prostate cancer hiding in the body that are too small to be picked up by standard imaging.

PSMA stands for prostate-specific membrane antigen, a molecule identified in the late 1980s that sits on the surface of prostate cancer cells.  Supported by many years of PCF funding, scientists have managed to link PSMA to radioactive tracers that can home in on this very specific molecule wherever it happens to be:  think of heat-seeking missiles locking onto a target.  Depending on the radioactive molecule linked to PSMA, it can either detect prostate cancer by shining a virtual spotlight on areas as small as a BB – the imaging technique the FDA has just approved – or detonate it with chemotherapy or tiny doses of radiation delivered by radionuclides at the cellular level.  In Europe and Australia, and in clinical trials in the U.S., PSMA-PET is being used to target and kill cancer in just those tiny outposts, leaving nearby cells unscathed.

“The PCF saw the potential of PSMA targeting way back in 1993,” says medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of PCF.  “Over nearly 30 years, we have invested more than $26 million in research on PSMA, with the goal of finding cancer that has escaped the prostate when it is very early and at a very small volume, because we believe that the sooner we can target it, the sooner we will be able to treat it and change the course of metastatic prostate cancer.”

The particular PSMA-targeted contrast agent that just got approved – a remarkable achievement in itself, based on five years of research by investigators Thomas Hope, M.D., at the University of California-San Francisco, and Johannes Czernin, M.D., and Jeremie Calais, M.D., MSc., at the University of California-Los Angeles – is called 68Ga-PSMA-11.  (The “Ga” stands for gallium; other PSMA agents are in various stages of getting FDA approval.)  And this particular FDA approval, for now, is for use on a very small scale:  only in California, at UCSF and UCLA.  But it’s a start – and it marks an important milestone in prostate cancer detection and treatment.  

This FDA approval is for use of PSMA-PET imaging in two main groups of patients (for now), says Hope, who is Director of Molecular Therapy in the Department of Radiology and Biomedical Imaging at UCSF: “in high-risk men before treatment with prostatectomy or radiation therapy, and in men who have already been treated for localized prostate cancer who have a rising PSA.

The strong collaboration among the PCF-funded scientists at UCLA and UCSF undoubtedly helped secure the FDA’s approval – itself a bit of a milestone.  “This is really unusual,” Hope notes.  “The FDA has never approved a drug at two manufacturing centers before, and both centers were approved on the same day.”

Achieving a PSMA-PET scan is more labor-intensive and expensive than patients might realize, Hope adds.  “We have to make the imaging agent ourselves in small batches,” a high-tech process that requires a gallium generator, and the solution can’t be stockpiled for long-term storage, because gallium has a half-life of a little more than an hour.  “For now, there is no commercially available PSMA-PET contrast agent,” but Hope believes this will change soon; two new drug applications for PSMA agents are under review by the FDA, and more are expected.

Note:  Many men won’t ever need PSMA-PET.  If you have a small amount of Gleason 6 prostate cancer and you are enrolled in active surveillance, or you were diagnosed with low- or intermediate-risk cancer that was treated with surgery or radiation and your PSA is undetectable, then PSMA-PET is probably not something you will need to consider.  But for other men – those with a rising PSA after treatment, for instance; men at high risk of cancer recurrence; or some men with metastatic prostate cancer – PSMA-PET can help determine what to do next.  As Hope says, “Now we know where it is.  The question then becomes, what’s the best way to treat it?”

Smarter Treatment

Having this extra insight shouldn’t be a scary prospect, he adds.  “It’s never bad to know; instead, what can we do with this knowledge?” One exciting thing is to treat men with oligometastasis, as oncologist Phuoc Tran, M.D., Ph.D., is doing at Johns Hopkins: and he’s going after a cure!   Another thing is to actually put the treatment where the cancer is, instead of where it is not.  Hope explains:  Many men who have a rising PSA after prostatectomy “get radiation therapy blindly to the prostate bed; 30 percent of those patients have a recurrence of cancer after about two years.  But with PSMA-PET, we know that about 30 percent of these patients have disease outside the radiation field.  Those are the patients who are recurring!  Now we can expand the radiation field to include known sites of cancer.  We assume the patient will benefit – we just haven’t proven it yet.  Do we not want to know where the disease is, and treat them blindly?” No! And this could be a game-changer for some men.

It’s also important to note that PSMA-PET is not the perfect crystal ball; it can’t detect areas of cancer that are really tiny.  Hope says that “some patients take a negative PSMA-PET to mean they don’t need any treatment,” and that’s not always correct.  “If you have biochemical recurrence (a rising PSA), and PSMA-PET doesn’t show any evidence of disease, the cancer is going to continue to progress.  Don’t think you don’t need treatment, particularly if you’re a candidate for salvage radiation therapy.”

These and other issues will become increasingly clear as PSMA-PET becomes incorporated into the standard of care.  As Hope notes, “It’s early days yet.”

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

I recently had the privilege of interviewing Peter Frampton (yes, THAT Peter Frampton!) for Johns Hopkins Rheumatology’s LEAP Magazine, and two things really struck me:  One, he is really a nice, decent guy.  And two, what he has taught his doctors about muscle memory and retaining function through repeated practice and hard work has changed the advice they give their patients.     

After all these years, legendary musician Peter Frampton sounds just as good as ever.  In fact (although he might disagree), to those who have heard him live or listened to some of his newer recordings, this beloved guitarist sounds even better than he did back in the days of his landmark 1976 album, Frampton Comes Alive! or Fingerprints, for which he won a Grammy in 2006.

This is remarkable for two reasons: first, he has an autoimmune disease called inclusion body myositis (IBM) that affects his muscles.  And second:  although he has experienced some weakness and loss of function in larger muscles, his fingers still work great!

Frampton’s finger dexterity was not at all what his doctor, rheumatologist Lisa Christopher-Stine, M.D., Director of the Johns Hopkins Myositis Center, expected to find; then again, neither was Frampton himself.

Before his first appointment, Christopher-Stine says, she wondered whether he would be one of those high-maintenance, dark sunglasses-wearing celebrities.  He wasn’t.  “He didn’t have an entourage; he’s just a very down-to-earth, lovely person.”  He is also consistently upbeat, with a can-do attitude, great sense of humor and a hearty laugh.  He has IBM, but IBM doesn’t have him.  “Sure, I have my darker moments,” Frampton says.  “But I have so much to be thankful for.  We all have our battles; this is mine, but everybody has something.  You walk down the street, and you’ve no idea what the person who just passed you is going through.  This has opened me up to be more empathetic about other people’s battles.  Yes, mine is serious, but there are many worse ones out there.”

Patient and Teacher

IBM is not the same in every patient, Christopher-Stine notes, “and it’s unclear why certain muscle groups are targeted more than others.”  The finger flexor muscles are often specifically affected in IBM and for that first visit, Christopher-Stine’s immediate concern was how badly affected they would be in the renowned guitarist.  She was in for a surprise.  His finger dexterity, built over decades of disciplined practice and virtuoso performance, was extraordinarily well-preserved, she says.

“I have noticed some changes,” says Frampton.  “They’re small.  I am very, very slowly losing power in my hands, so that’s a little disturbing.  But so far, because I’ve been playing all my life, as soon as I take up a guitar, they tend to know what to do.”

Because of Peter Frampton, Christopher-Stine has changed her advice for patients with IBM.  “In many ways, he’s been a teacher, as much as a patient,” she says.  “He taught me how important exercise and recurrent use of one’s fingers are.  Remarkably, his left hand, which plays the frets, is even stronger than his right hand, which is his dominant hand!   I started recommending to other patients to get a guitar or piano – just start playing.  I don’t know that we can undo damage that was already there (in other patients), and it is unlikely that people who don’t play at that high level would get the same benefit.  But he has proven that there is a benefit in isolating our finger flexors individually; most people don’t do that.  We tend to concentrate on grip testing and strengthening rather than on individual finger muscles.”

Exercise is Non-Negotiable

In addition to practicing and playing guitar, Frampton does a one-hour workout six days a week.  This is non-negotiable; even the pandemic and gym shutdowns haven’t stopped him.  “I’m very lucky; I do not have the swallowing problem (these muscles can be affected in IBM),” he says. With the help of a personal trainer (online during the pandemic), he exercises “every muscle that is affected,” in his case, “the muscles in the legs, the arms and the hands.  We mix it up:  legs and core, then core and arms another day, so it’s always different.

“I am aware of the very slow decline; stairs are a real problem for me.  We concentrate on fall prevention:  that’s the way I found I out I had this, the reason I went to a neurologist in the first place.  I fell twice on stage within a month.  I had no idea what was going on.  I knew I was losing power in my legs, but I really didn’t have a clue as to what was going on.  I actually thought my tight jeans were impeding my walking!  The mind is a terrible thing!”

That was six years ago.  During a 10-day break in his concert schedule, Frampton went to a neurologist, who narrowed down the diagnosis to two possibilities.  “He didn’t tell me until after he’d diagnosed me with IBM that the first one on his list was ALS (amyotrophic lateral sclerosis).  Because it is so slow-moving, IBM is hard to diagnose.”

Giving Back

And because it is pretty rare, affecting maybe eight out of every one million Americans, IBM has not garnered huge research funding; neither has it been a big focus of drug development by pharmaceutical companies. Frampton is doing his best to change this, establishing the Peter Frampton Myositis Research Fund at Johns Hopkins to raise money for research.  In February 2019, he went on “CBS This Morning” to announce the Fund and his 51-date U.S. Farewell Tour.  “Each promotor donated a dollar from every ticket sale,” he says.  “The Shriners teamed up with us,” selling copies of Frampton’s 2019 CD, All Blues.  “I didn’t see any money from that CD:  half the profit went to the Shriners, and half of it went to my fund at Johns Hopkins.”  So far, the tour and CD sales have raised more than $300,000.

“The promotors had to do this themselves.  They had to work out how many people were there, they had to write a check after every one of my concerts in different places, and they all sent in the money,” Frampton says.  “In fact, in a couple places, they gave a huge check on top of that.  People were just so behind the Fund and doing as much as possible.”

“Symbol of Hope”

Since he went public with his diagnosis, “he’s become a symbol of hope,” says Christopher-Stine, who gets calls and letters from patients saying that Frampton has inspired them.  Frampton makes time to talk to “other IBM’ers,” on the road and online.  On the Farewell Tour, “I would do a VIP meet and greet at the end of each concert, usually about 40 to 50 people,” he says, “and if there were any IBM’ers, we left them until last, so I could spend more time with them.”  He remembers one couple in particular:  “They didn’t say that he had IBM, they didn’t wait until the end, so we didn’t know.  So I’m standing in between them, and I’m signing their stuff and getting ready to take a picture, and the wife says, ‘You diagnosed my husband.’  I said, ‘Excuse me?’  He was very quietly spoken, and he said, ‘I had been to I don’t know how many doctors.  Nobody knew what I had, and nobody could help me.  I watched you on CBS, and everything you said, all your symptoms, I ticked them off one at a time.  I just yelled at my wife, ‘Hey, come in here!  Frampton just diagnosed me!  I’ve got IBM!’  He went to a neurologist, because that’s what I said to do, if you’ve any weakness in your leg muscles and no clue what it is.”  Frampton asked the man if he was exercising now, and the answer was, “’Every day.’  There was proof that I had actually helped someone by talking about it on TV.”  (Note:  this particular story has already helped someone, who had been diagnosed with IBM and told by his doctor NOT to exercise, for fear he might fall.  He got a new doctor, and has started an exercise program.)

Inherited Resiliency

Christopher-Stine says of Frampton, “I feel so fortunate to know him.  He is truly a remarkable human being.”  Frampton says his positive attitude is inherited.  “My kids say to me, ‘Dad, how come it’s always the little, tiny things that really bother you?  When something big happens, good or bad, you take it in your stride.’  I don’t know, but I’m the problem-solving optimist of the family.  I got that from my parents.  I was born five years after my dad came back from Germany in the second World War.  I learnt so much from their stories.”  His father fought in Europe and Africa.  His mother survived the Blitz.  Over time, “she got fed up with going to the bomb shelter in the basement, so she just stood out on the balcony and watched the bombs come down.  Every day, they woke up and didn’t know if it would be their last.”

They were glad to be alive, and so is Frampton.  “I just feel like, if I’m the face of IBM, then I think you’ve got the right person, because I never give up!”

Photo courtesy Austin Lord.

©Janet Farrar Worthington





This is an update to a story I wrote five years ago, for Johns Hopkins Rheumatology’s LEAP Magazine, with two world experts on PTLD: post-treatment Lyme disease.  They have uncovered some promising clues as to why, for some people, Lyme disease doesn’t go away, and identified some new potential avenues of treatment.

Some people get bitten by a deer tick that’s infected with Borrelia burgdorferi, develop a rash, are diagnosed with Lyme disease, take antibiotics, feel better, and get their life back to normal.

Others aren’t so lucky.  Diagnosed just as promptly, they take the exact same course of antibiotics.  And then…  they don’t get better.  What’s happening?

John Aucott, M.D., an infectious diseases specialist and the founding Director/physician of the Johns Hopkins Lyme Disease Research Center, is a world authority on this “post-treatment Lyme disease” (PTLD), a condition he helped define.  Its symptoms are persistent, and can include fatigue, pain, weakness, brain fog, and sleep disorders. He has studied and treated hundreds of patients with PTLD, who tell him things like, “I can’t get out of bed,” or “I can’t ride my bike,” or “I’m exhausted trying to get through the work day.”  In addition to feeling ill, frustrated, discouraged and even desperate for relief, these patients often must deal with a stigma – similar to that experienced by a brand-new group of patients from the pandemic, the Covid-19 ‘long-haulers,’ Aucott says.  “The Covid long-haulers aren’t dying, they don’t have signs of extensive organ damage – but they have the exact same lingering, disabling symptoms that we have been pointing out for years in our PTLD patients.”

Aucott and his longtime colleague, scientist Mark Soloski, Ph.D., suspect that for the PTLD “long-haulers” – about 10 to 15 percent of people treated for acute (initial) Lyme disease – the disease process triggers persistent changes in the immune system and the autonomic nervous system.  Their pioneering research program focuses on defining and characterizing changes in the underlying molecular mechanisms that cause and perpetuate these symptoms, with the hope of finding biomarkers to help diagnose and monitor this disease, and to discover new avenues of treatment.  Their areas of active study include:

The gut microbiome:  In work recently published online in mBio, Soloski, Aucott and colleagues at Hopkins, Northeastern University, and University of California-San Diego reported that PTLD patients have a distinct microbiome “signature,” or population of bacteria in their gastrointestinal tract compared to healthy controls and to an intensive care unit control group.  The scientists analyzed fecal samples from patients in the Hopkins Study of Lyme Immunology and Clinical Endpoints (SLICE), and compared them to a healthy control group and to an intensive care unit (ICU) control group – patients who were also on antibiotics.   “We found that the PTLD group had two distinct differences in their gut bacteria – an abundance of Blautia bacteria, and a decrease in Bacteroides,” says Soloski.  “Bacteroides is interesting, because it produces GABA, an important neurotransmitter.”  Low levels of GABA can cause anxiety and depression.  In turn, an excess of Blautia has been found in people with obesity, Alzheimer’s disease, and multiple sclerosis.  The good news about the gut microbiome is that it can be altered by many factors, including diet, medication, and even fecal transplant.  It may be that reintroducing healthy bacteria into the colon could significantly improve quality of life in these patients – a compelling idea that the investigators feel is worthy of further study.

 The metabolic response:  In another study, Soloski, Aucott and colleagues at Hopkins, the centers for Disease Control, Colorado State University, and New York Medical College found significant metabolic differences in people with PTLD compared to other patients.  This work was published in Clinical Infectious Diseases.   “Basically, we found that the metabolome – all those small molecules our cells make and pour out into our blood, our signature of the metabolic activities of all the cells in the body – is perturbed in patients with Lyme disease.”  The scientists have identified a “fingerprint” of metabolites unique to patients with PTLD.  This might one day lead to a blood test to determine which patients with Lyme disease are at risk of PTLD, and to help monitor the course of illness in PTLD patients.

Is there a genetic fingerprint?  Soloski and Aucott are looking for epigenetic changes – small mutations in the structure of DNA – among the 20,000 or so genes in the genome.  This is big-data analysis that wouldn’t have been possible a few years ago.  Computers and data experts sift countless pieces of evidence, like miners sluicing for gold, looking for valuable nuggets:  patterns of gene expression, particularly in immune system genes and in messenger RNA genes.


Not Always a Bullseye

Artificial intelligence (AI) is making possible what John Aucott describes as his “pet project:” analyzing the rash that comes at the start of Lyme disease and is key to early diagnosis.  “Our studies show that many people have trouble making the right diagnosis.  Everybody’s looking for the Target store sign,” but that distinctive bullseye only appears in 20 percent of patients.  “Patients and clinicians miss the other 80 percent.  We trained the computer by AI to read cell phone images and make a better diagnosis.”  Aucott was senior author on a report of this work, recently published in Computers in Biology and Medicine.

Could rashes even help predict which patients might be headed for PTLD, and could a better understanding of rashes lead to more effective, personalized treatments?  These are possibilities Aucott hopes to explore.


Better treatment for PTLD

            “There is no FDA-approved treatment for PTLD,” says Aucott, “so we use drugs that the FDA has approved for other indications.  Treatment is very patient-specific, depending on the primary symptoms.”  For example, fatigue often goes along with postural orthostatic tachycardia syndrome (POTS), a condition where the heartbeat skyrockets with a change of position – from sitting to standing, for example – that is treated by blood pressure-regulating drugs such as midodrine.

            In exciting research recently published online in BMJ Open, Hopkins scientists Alison Rebman, Ting Yang, and Aucott, have identified six symptom factors and three potentially clinically relevant subgroups among patients with PTLD.  The group’s findings may be an important step toward developing even more personalized and specific treatment plans. 

Aucott has spent years working to raise physician awareness about PTLD, which “doesn’t fit into one specific disease silo” or subspecialty; in fact, the Center is the only one of its kind based in an academic department of medicine in the world with a focus on PTLD.

New to the Center is rheumatologist John Miller, M.D., who brings expertise in joint ultrasound.  “He is showing changes in our patients that are subtle,” particularly “tendinopathy-related causes of periarticular pain that nobody’s seen before, because joint ultrasound has never been done in these patients.”  Miller has found enthesitis, inflammation where tendons insert into the joints that is also found in psoriatic arthritis and Reiter’s syndrome (reactive arthritis).  His findings “may lead to looking at autoimmune-related drugs,” says Aucott, and the images “are opening up a whole new field of clinical inquiry.  Nobody else is really doing this.”

You can learn more about the Center here.

©Janet Farrar Worthington