– Bonnie Crater, founder and vice-chair of the Board of Directors, Bay Area Lyme Foundation

What does an anti-alcoholism drug have to do with Lyme disease? Nothing—until a 2016 study funded by Bay Area Lyme Foundation found a link. From around 2014 through 2017, two labs on opposite coasts—one at Johns Hopkins University and one at Stanford—were testing thousands of FDA-approved drugs to identify an existing drug that worked against “persister” forms of Borrelia burgdorferi (Bb), the bacteria that causes Lyme disease(1,2,3,4). Why were they doing this?

Here’s a little background. Borrelia burgdorferi, a spirochete, when cultured in a lab has roughly 3 different forms: a) a culture with predominantly long or corkscrew forms, b) a culture with predominantly round forms and some microcolonies, and c) a culture with predominantly microcolonies (2). Most laboratory studies regarding the effectiveness of antibiotics are conducted in cultures on long forms. In this long form, the spirochete is motile and can divide (although very slowly) and consequently, some antibiotics work much better on the long form. However, after exposure to antibiotics such as doxycycline, the spirochete curls up into a round form and some clump together with other spirochetes to form a few microcolonies. These round-body and microcolony forms are understood to be a defensive posture for the bacteria.

For patients who have the chronic form of Lyme disease, it is hypothesized for the purposes of finding better antibiotics that these patients have persister forms of the bacteria. Dr. Kim Lewis, research professor at Northeastern University published his paper in 2015 and stated matter-of-factly Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells. And while Dr. Lewis’s work is in the lab (and not on animals or humans), his work has been corroborated by others who found persister Borrelia in mice, dogs, primates, and humans (6-11). In addition, it is widely known that inflammation is a big challenge for chronic Lyme patients which makes them feel poorly overall and have chronic pain symptoms. Consequently, Bay Area Lyme Foundation’s search for new treatments for chronic Lyme conditions included the ability to eliminate all forms of Bb as well as to reduce chronic inflammation associated with Lyme disease.

The exploration of FDA-approved drugs as a Lyme therapeutic is a key strategy for Bay Area Lyme Foundation on our mission “to make Lyme disease easy to diagnose and simple to cure.” Our approach for the last five years has been pretty straightforward: (1) identify borreliacidal drugs in vitro (translation—drugs that kill Bb in a lab), (2) pick the winners and put them into mouse studies and (3) pick the mouse study winners and put them into a clinical trial.

Could we find drugs used for other purposes that kill Borrelia and reduce inflammation? We didn’t know. But Dr. Jayakumar Rajadas, director of Stanford University’s BioADD lab, was on a mission. Dr. Rajadas’s empathy for Lyme patients was notable and he was determined to see if any in a library of FDA-approved drugs would kill long and persister forms of Borrelia and help patients feel better by eliminating the infection and reducing inflammation.

In Dr. Rajadas’s 2016 laboratory study, Identification of New Drug Candidates Against Borrelia burgdorferi using high-throughput screening, post-doctoral researcher Venkata Raveendra Pothineni dedicated himself to the task of running a set of tests on 4,366 FDA-approved compounds. Of the over 4000 drugs screened for activity against Bb, Tetraethylthiuram disulfide was the top candidate. Tetraethylthiuram disulfide, also known as disulfiram and branded Antabuse, is an anti-alcoholism treatment that literally makes a patient have a massive hangover if he or she drinks any alcohol. Disulfiram is known to also have antibiotic properties. (5)

After reading Dr. Rajadas’s 2016 high-throughput screening paper, Dr. Kim Lewis became very curious about disulfiram and ran his own tests with some very interesting results. In October of 2016, Dr. Lewis presented his lab’s work as part of a keynote speech for the Mount Sinai School of Medicine 1st Annual Symposium: Lyme Disease in the Era of Precision Medicine which was sponsored by the Steven & Alexandra Cohen Foundation in New York City. During that speech, Dr. Lewis mentioned the work of Dr. Rajadas’s group showing that disulfiram was a very potent agent against Borrelia burgdorferi persisters. A video recording of Dr. Lewis’s keynote was placed on YouTube. Sometime after that, a patient of Dr. Ken Liegner, who had been following Dr. Lewis’s work, discovered the YouTube video recording of Dr. Lewis’s speech. This individual, an engineer, was doing fairly well on intensive anti-microbial treatment for both Lyme disease and babesiosis but whenever treatment was suspended, he deteriorated with returning symptoms. Like many Lyme patients, the engineer combed the internet for improved methods of treatment that could keep him well.

After finding the YouTube video and bringing it to Dr. Liegner’s attention, the engineer requested Dr. Liegner to start a treatment with disulfiram. The engineer has remained clinically well without need for further treatment for more than two years. Dr. Liegner, who read the publication by Drs. Pothineni and Rajadas which was the basis of Dr. Lewis’s comments, contacted Dr. Rajadas to learn more about his work. After treating several patients with disulfiram, Dr. Liegner published a case series in May 2019 which described his experiences with use of this drug. While not every patient has had as dramatically favorable an outcome as the engineer, Dr. Liegner remains very impressed by the utility of disulfiram and has not seen such dramatic results with the application of any other agent during his 30 years of practice in treating individuals suffering from chronic Lyme disease and chronic babesiosis.

Since then, other physicians have started prescribing disulfiram for patients, including Dr. Richard Horowitz of Hyde Park, New York. In addition, Bay Area Lyme Foundation funded a mouse study with Dr. Monica Embers at Tulane University, Dr. Brian Fallon of Columbia University has initiated a pilot clinical trial, and Dr. Rajadas has continued his work to identify an improved formulation for disulfiram and worked to demonstrate borreliacidal and anti-inflammatory activity in mice. In addition, several Facebook groups have formed for patients are sharing their experience with disulfiram.

While the effectiveness of disulfiram has not yet been evaluated by formal clinical trials and the exact mechanisms by which it exerts its effects on Borrelia is still in the early days of discovery, we know at least some chronic Lyme patients seem to be benefiting from its use. I think we can all be grateful for that. The story of disulfiram is also a story of collaboration across physicians, scientists, foundations, and patients, who are all seeking a cure for Lyme disease. And let the scientists and clinicians continue to collaborate carrying on this important work, while the rest of us cross our fingers that maybe we have gotten lucky and we’ve found a solid treatment that is inexpensive, oral, and relatively safe for chronic Lyme disease.

As a final word, we are not physicians or clinicians at Bay Area Lyme Foundation. If you are a tick-borne disease patient interested in disulfiram, please consult your healthcare provider for further information.

DRUG SCREENINGS REFERENCES:

(1) Feng J, Wang T, Shi W, Zhang S, Sullivan D, Auwaerter PG, Zhang Y. Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library. Emerg Microbes Infect. 2014 Jul;3(7):e49.

(2) Feng J, Auwaerter PG, Zhang Y. Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline. PLoS One. 2015 Mar 25;10(3):e0117207

(3) Rajadas J. Identification of new drug candidates against Borrelia burgdorferi using high throughput  screening, Dovepress 1April 2016: Vol 2016:10 p1307-1322

(4) Pothineni VR, Wagh D, Babar MM, Inayathullah M, Watts RE, Kim KM, Parekh MB, Gurjarpadhye AA, Solow-Cordero D, Tayebi L, Rajadas J. Screening of NCI-DTP library to identify new drug candidates for Borrelia Burgdorferi. J Antibiot (Tokyo). 2017 Mar;70(3):308-312.

(5) Long TE. Repurposing Thiram and Disulfiram as Antibacterial Agents for Multidrug-Resistant Staphylococcus aureus Infections. Antimicrob Agents Chemother. 2017 Aug 24;61(9). pii: e00898-17.

ANIMAL STUDIES REFERENCES:

(6) Barthold SW, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ. Ineffectiveness of tigecycline against persistent Borrelia burgdorferi. Antimicrob Agents Chemother.2010;54(2):643-651.

(7) Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following –

(8) antibiotic treatment in mice. Antimicrob Agents Chemother. 2008;52:1728-1736.

(9) Straubinger RK, Summers BA, Chang YF, Appel MJ. Persistence of Borrelia burdorferi in experimentally infected dogs after antibiotic treatment. J Clin Micobiol. 1997;35(1):111-116.

(10) Embers ME, Hasenkampf NR, Jacobs MB, Tardo AC Doyle-Meyers LA, Philipp MT, Hodzic E. Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding. PLoS One. 2017; 12(12):e189071.

(11) Nocton JJ, Dressler F, Rutledge BJ, Rys PN, Persing DH, Steere AC. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Eng J Med.1994;330:229-234.

(12) Lawrence C, Lipton RB, Lowy FD, Coyle PK. Seronegative chronic relapsing neuroborreliosis. Eur Neurol. 1995;35(2)113-7.

(13) Chancellor M, McGinnis P, Kilholma P, Hirsch I. Urinary dysfunction in Lyme disease. J of Urol. 1993;149(1):26-30.

DISULFIRAM, CLINICAL APPLICATION FOR LYME DISEASE, REFERENCES

(14) Liegner, Kenneth B. (May 2019). “Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases”. Antibiotics. 8 (2): 72. doi:10.3390/antibiotics8020072

18 Comments on “In Search of a Cure for Lyme Disease: The Disulfiram Story

  1. Christine Jonckheer wrote in Dutch:
    Wonderful !!!! Are the side effects so bad? I react very fiercely to many treatments. Do you have to take it for life? Can any doctor prescribe it and does it cost a lot? (financial well after 20 years of illness and all kinds of treatments) Thankful if you want to answer me.

    My answer:
    I’m in the middle of my treatment. It is very important to take Disulfiram LOW AND SLOW and if you do this you can control most of the BAD side effects. You do not need to take it for life. I hope 6 months will be enough. I visited Dr Wolfgang Klemann in Pforzheim, Germany to get the prescription. He also gave me laboratory orders to be able to test liver, kidney and blood every 3-4 weeks. The cost is approximately 25 euro/month.

  2. This is the first possible treatment I have found for my dear suffering Husband. He has plenty of symptoms and neuropathy in a wheelchair from being an active strong man to this…:-( Galaxy labs found Bartonella and Babesia. Our LLMD will not give us this drug at this time. Please how can we get this drug. Nothing has been working and it has cost us thousands. Our LLMD is very cautious about it and now has him on ABART and Mino low doses building up incrementally. But it has been 2.5 years already and 30 drs. We need help. Please let us know what you can do. I am Carmen, his Wife. thank you!!

  3. I have found some benefit from disulfiram and I’m reading many success stories on Facebook. I had to stop due to side effects but will likely restart at a lower dose. We need follow up studies to determine the best course of treatment and work to improve drug delivery and stability so a lower dose can be used with fewer side effects. Please fund more of this important work.

    1. May I ask what your side effects were? I have been on 125mg for the past two weeks and just increased to 250mg yesterday. In two more weeks, I will increase to 500mg. I have been very tired and sleepy since beginning Disulfiram, also spacey and lightheaded. It’s always hard to know if its a side effect from the drug or an increase in the chronic Lyme symptoms. Thank you and I wish you the best!

  4. Thank you Bay Area Lyme for writing such a clear piece about this discovery and how it has become popular. I hope it is shared everywhere and Jayakumar Rajadas’ lab receives FULL credit and additional funding to continue their work for us patients. I have been on it for 6 months now including a 6-week break and feel soooo GOOD! I’ve treated for 7 years to no avail with drug combos, ozone, herbals, homeopathy, LDI, etc. and still got Lyme and coinfections back!

    This drug is not easy at times but NOTHING patients should be afraid of using a low and slow approach. A lot of the fear that has circulated in a support group has been from people NOT on the drug and from those who tried to go too high and too fast. There is good patient support in a healing environment at Disulfiram for Lyme Group. Anyone can PM me for questions or join us in our group to learn about the drug and how it might help you or a family member. My Dr just called it the cure for Lyme yesterday. COMPLETELY FLOORED ME! He’s not the only one saying that! I hope BAL will support this lab with as much funding as they can.

    1. Prachtig!!!!Zijn de bijwerkingen zo erg? Ik reageer nl heel heftig op veel behandelingen. Moet je het levenslang nemen? Kan elke dokter het voorschrijven en kost het veel? (financiele put na 20 jaar ziek en behandelingen allerlei) Dankbaar als u me wil antwoorden.

    2. Hi, Good info. Suffering for over 12 years. 3 months of IVs, the works. Felt toxic from antibio. How did you know coinfections were back?. Put in for three months of disulfiram. Wish me luck. Tired of being crash test dummy.

    3. Thank you so much for the information, Kristina. I have Lyme Carditis and pretty much every other physical and neurological symptom with increasing severity over the past 3 years. I would love to join your group and discover what others are doing with Disulfiram. I’m particularly interested in what I may expect, recommended dosage, what groups have seen the most positive impact, and finding some fellow sufferers I can relate with. Thank you!! Brandon Capes

    4. Please let me know how to get into the Disulfiram for Lyme Group. My husband’s doctors just prescribed this for him today. Thank you

  5. Thank you for posting this story about the ground-breaking work done by Dr Rajadas’ and Venkata Pothineni‘s amazing team for the treatment of chronic and acute Lyme disease. Their discoveries of medications that are actually effective in treating patients who have been sick for years are nothing short of revolutionary. This small group of researchers has accomplished more in a few years than has been done in the past 35+ years. These scientists are, truly, the largely unsung heroes who deserve our admiration and support to continue their efforts to give Lyme patients back their lives.

  6. I am very excited to read your article! This is printed and will be taken to two of my doctors along with other important articles on Disulfiram and pioneer Drs and researchers. The FB Disulfiram Support Groups are being followed daily and I watch carefully the posts.

    I believe these infections are the root cause of many serious debilitating “diseases,” including suicide to escape. It is a living hell to suffer from all the miserable life-sucking symptoms. Please know we are so grateful for the devoted pioneers and true humanitarian researchers.

    Bless you all and God speed your works. Waiting for a cure🙏🏼

    1. Bay Area Lyme is excited about the promise of this research to offer real therapeutic relief for Lyme patients and also for the collaboration and innovation which it represents. We hope to continue to support efforts like these. You can find more information about how to donate here.

  7. I am a rare 29-year late-stage Lyme, with Babesia duncani client with cardiac interested pathogens and I have many colonies. I am a nutritionist or I would not be here. I am interested in this drug. I would like to be contacted.

    1. They will not contact you. Call all the ILADS doctors in your state and ask if they offer this. ILADS has a list per state on their website.

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