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Clinics across the U.S. are claiming to treat cancer, Lyme disease, and other bacterial and viral infections with "supportive oligonucleotide therapy (SOT)" -- a treatment lacking both data and FDA approval.

The name piggybacks off the success of more than approved by the FDA over the last quarter-century, including treatments for Duchenne muscular dystrophy, spinal muscular atrophy, and other rare diseases.

Many of the clinics are run by physicians or nurse practitioners, but some also have ties to naturopathic doctors. They lure patients with the promise of personalized treatment for difficult-to-fix conditions.

"Once this is in your body, it's almost magical," said in a , a network of integrative medicine clinics. "It can actually cause existing viruses and bacteria and Lyme organisms to die. It also prevents replication. So it's just a really great remedy, and we're seeing some really great results."

But there's no evidence that SOT works, save for two small and limited papers published by the Greek research team that appears to be the key supplier of tailor-made SOTs to U.S. clinics.

Mark Kay, MD, PhD, professor of genetics and pediatrics at Stanford University in California, said it sounded like a "scam."

"It really upsets me when I see this, because these things aren't benign. They do cause side effects," Kay told MedPage Today. "If you treat enough people, someone may have irreversible problems at some point, and none of this is doing any good."

What Is SOT?

Oligonucleotides are short strands of DNA or RNA that can play a role in the regulation of gene expression. Two main types of oligonucleotide drugs on the U.S. market are antisense oligonucleotides (ASOs) and short interfering RNAs (siRNAs).

Essentially, ASOs and siRNAs work by binding to much larger messenger RNA to regulate gene expression and ultimately manipulate the production of proteins, whether to increase them or shut them off.

FDA-approved ASOs include mipomersen (Kynamro) for homozygous familial hypercholesterolemia; eteplirsen (Exondys 51), golodirsen (Vyondys 53), viltolarsen (Viltepso), and casimersen (Amondys 45) for Duchenne muscular dystrophy; and nusinersen (Spinraza) for spinal muscular atrophy. siRNAs include patisiran (Onpattro) and inotersen (Tegsedi) for hereditary transthyretin amyloidosis.

Each of those compounds went through clinical trials and received FDA approval, unlike the SOT treatments being pitched by U.S. clinics.

In her video, Casebolt describes how patients first have a blood test to determine which pathogens they have, and then a blood sample is sent to the lab in Greece, which prepares the SOT based on those microbes. The tailor-made oligonucleotides then reportedly target bacterial genes involved in replication.

Casebolt says the "overall effects can be astonishing," and cited the case of a patient with Parkinson's disease who, after treatment with SOT, could play the violin again for the first time in 6 years.

Clayton Bell, MD, who works at a Forum Health clinic in Asheville, North Carolina, told MedPage Today that he has taken 10 SOT treatments for symptoms of tick-borne bacterial infections, and believes it has helped him.

He said he understands that clinicians may be "skeptical" because the treatments don't have "robust, clinical, double-blind, placebo-controlled trials" behind them; nor do they have FDA approval (though he said they don't need FDA approval because they're regulated as human cellular and tissue-based products, "like a PRP [platelet rich plasma] or like a stem cell").

"I've found it clinically to work. Not every time, but no medicine does," he said. "But when you use it judiciously, in the correct context with the right patient and the right support, I have found it to be very effective in a high percentage of cases."

Forum Health is hardly the only clinic offering SOT. A Google search yielded more than a dozen clinics -- in California (, , and ), , Indiana ( and ), , , , New York ( and ), , , and Utah ( and ).

Most of these clinics cite the Research Genetic Cancer Center (RGCC), based in Greece, as the place where the SOT is made and then shipped back to the U.S. for intravenous infusion.

Made in Greece

Ioannis Papasotiriou, MD, PhD, is the founder of RGCC, which advertises "personalized cancer testing" .

Papasotiriou is the corresponding author on the only two papers on SOT found in PubMed. The first, , is a preliminary study in 95 patients with cancer who received SOT. It reports that the majority of patients had a "positive" response to treatment, based on a composite of follow-up assessments for tumor response, but there was no control group.

The , published in December 2022, concluded that SOT reduced the amount of DNA of Borrelia burgdorferi, a bacteria that causes Lyme disease, and other viruses in the blood of 115 patients.

It's not clear exactly what type of oligonucleotide is made for the therapy. The Lyme disease trial describes a siRNA, while an describes an "antisense therapy."

RGCC has not returned a MedPage Today request for comment as of press time.

"We don't even know exactly what they're making," said Kay of Stanford. "siRNAs are different from ASOs but can accomplish some of the same things. They can knock down a gene product that you want to knock down."

However, it's not clear that either technology would work in bacterial cells. "As far as I know, there hasn't been any success in treating infectious diseases" like Lyme disease, Kay said. "Molecules would have to get into the bacterial cells to kill them, because you're targeting bacterial genes. As far as I know, this hasn't been accomplished yet."

Also, delivery has long been a challenge with oligonucleotides, which can be rapidly destroyed by the immune system, Kay said. They may be eliminated before they can get where they need to go.

Finally, he added, "if this was so simple, I think companies would have jumped on this to do appropriate preclinical and clinical trials."

Subject to FDA Regulation?

Paul Knoepfler, PhD, a stem cell biologist at the University of California Davis, who , sees between the clinics giving patients SOTs and the stem cell clinics that the FDA has long been trying to regulate.

Stem cell products given out at clinics across the country have been linked to infections and severe adverse events, including hospitalizations. In 2021, the FDA mandated that all such treatments would need to be regulated as drug products -- not as human cellular and tissue-based products as they had long claimed -- or would require an investigational new drug (IND) application to be in place before being given to patients.

Yet many products continue to be sold, unregulated and without substantial clinical trial evidence to support them.

"I'm especially concerned about the cancer side of this as I don't see any good evidence to support that SOT would work for cancers and there could be many risks," Knoepfler told MedPage Today in an email. He pointed to an that "instructs cancer patients to stop taking some drugs like cytotoxic therapies, which are traditional cancer therapies, a pause that could pose risks."

Knoepfler believes that any oligonucleotide therapy -- even one that may be based on a patient's own blood samples -- would need to be regulated as a drug product by the FDA.

The agency has not returned a MedPage Today request for comment as of press time.

"Just because the FDA has approved a few other specific antisense or other related therapies doesn't mean that SOT would get approval," Knoepfler . "It would depend on the data."

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