US clinics widely selling unproven RNA therapy, supportive oligonucleotide therapy or SOT, from Greek firm RGCC

Reported outcomes of SOT for different types of cancer.  In my view such published preliminary data do not provide a solid basis for already ongoing commercial clinical use of SOT in human patients in the US. The purported response rates seem unusually high to me too. Fig. 3 from the SOT paper in the journal “in vivo” 2022. PR is partial response, CR is complete response, and SD is stable disease. PD is “progress disease”.

What is supportive oligonucleotide therapy or SOT?

SOT is an RNA product delivered IV and intended to invoke an antisense-like response to try to treat human diseases. The idea seems to be to silence specific pathogenic gene expression upon which the disease state would depend. What data are out there on this specific approach?

I found  just 2 papers on SOT on PubMed, both from RGCC, which appears to supply SOT to US clinics for use in patients:

• Supportive Oligonucleotide Therapy (SOT) as an Alternative Treatment Option in Cancer: A Preliminary Study. 
• Supportive Oligonucleotide Therapy (SOT) as a Potential Treatment for Viral Infections and Lyme Disease: Preliminary Results

These late 2022 papers report small, largely uncontrolled studies. As the paper titles indicate, they have only preliminary results. Note that if you are interested in more background, you can check out this SOT therapy patient guide as well. Despite the only 2 published studies, the patient guide, in regard to the question of whether SOTs are safe, says, “Yes, they have been assessed in thousands of studies for their safety.” Thousands?

Note that SOT is sometimes also called “Supportive Oligonucleotide Technique” so I searched for that too but found no articles.

I’ve posted a figure above from the SOT-for-cancer paper reporting potential responses in patients with various types of cancer.  The data, which in some cases report very high response rates compared to traditional, proven treatments like chemo, leave many questions unresolved. For example, are these numbers reflective of something positive happening within the tumor itself? Do fewer patients actually die over a period of years following SOT?

The cancer-for-SOT paper states this for ethical approval, “The study was reviewed and approved by the Bioethical Committee of the Research Genetic Cancer Centre Group.” RGCC approved its own study?

Given all this uncertainty, I was concerned to find SOT so widely available in the US.

Is SOT RNA therapy an unapproved drug in the US?

Since the marketed goal is to treat serious medical conditions including cancer and Lyme disease, in my view it is likely that supportive oligonucleotide therapy or SOT may be a drug therapy when used in the US. If I’m right about that, then SOT would require pre-market approval from the FDA.

Yet I can’t find any evidence that SOT is FDA-approved or even has an IND for clinical trials in the US. I’m not aware of any other oligonucleotide therapy (e.g., antisense therapy) marketed in the US without FDA approval. Of course, only the FDA makes determinations about whether something is a drug.

Note that just because the FDA has approved a few other specific antisense or other related therapies doesn’t mean that SOT would get approval. It would depend on the data. Furthermore, just because there have been clinical trials on other antisense approaches also does not necessarily mean SOT is safe or effective.

A physician Marty Ross, MD, who sells supplements for Lyme disease, wrote an interesting piece on SOT where he also mentions numerous concerns: Is SOT for Lyme & Tick-borne Infections a Scam? He also views SOT as a non-FDA-approved drug (emphasis mine):

“The clinics currently offering SOT therapy in the U.S. are purchasing non-FDA-approved SOT drugs from a Greek genetic laboratory called Research Genetic Cancer Center (RGCC).”

He also lists several potential issues with the SOT paper on Lyme disease.

Technical questions on SOT

As a molecular biologist and geneticist, I have many questions on SOT including about its purported use for cancer.

What are the sequences of the RNAs used against cancers? How are sequences chosen for safety and efficacy? Are they tested such as in cultured cells or animals in each case prior to use in patients? From the SOT cancer paper, they are “designed and produced based on circulating tumor cells’ (CTCs) gene expression profile.” How does that work exactly?

It’s also important to emphasize that just because you knock down the expression of one or more genes in CTCs doesn’t mean those cells will outright die. Even if you suppress a key anti-apoptotic gene, while widespread CTC death is possible, it is not a given. It’d have to be proven in each case. I also wonder what percent of CTCs that SOT gets into via IV administration. Do SOTS address the primary tumor in cases of solid cancer?

Another question comes to mind. How is the actual SOT RNA produced in a lab for clinical use? From the SOT-for-cancer paper by RGCC researchers:

“SOT production – administration. Following the validation of siRNA, modified dsRNA molecules were designed and produced using the Oligomaker48 DNA/RNA Synthesizer. dsRNA molecules were then freeze-dried and tested for the presence of pathogens as well as for the tightness of each tube and send to the clinicians. Upon arrival, SOT was reconstituted in 1 ml of water for injection and dissolved. Then, the solution was placed in a syringe and added 9ml of water for injection. The final solution was applied intravenously.”

Do researchers make the dsRNA in a standard molecular biology research lab or a clinical-grade lab? Wouldn’t it have to be a cGMP facility to be safe for patients? Is the IV route of administration appropriate?

What about the choice of dose?

Clinical trials on SOT RNA therapy?

I believe rigorous, large-scale clinical trial work should be required before using a new RNA therapy for cancer. Otherwise you just can’t be sure about things like dosage as well as possible efficacy and safety. Yet I found no results on Clinicaltrials.gov for search for SOT or supportive oligonucleotide therapy. Note that not every trial is listed on that site, but many international trials are on Clinicaltrials.gov. I call SOT “unproven” because in my view there is insufficient clinical evidence to back up its use being safe and effective.

Supportive oligonucleotide therapy could have risks. For example, such an antisense-type function could hit unintended target genes, like tumor suppressors or any number of other genes, predisposing recipients to unwanted effects. Oncogenes could indirectly get activated.

This kind of approach is very complicated. Many genes that are mutated or have elevated expression in cancer also in parallel often perform crucial normal functions in healthy cells including stem cells. For instance, I’ve been studying MYC family genes for more than 20 years. They may have roles in most types of cancer, but they are required for normal cell behavior too. Strongly suppressing MYC expression throughout the body including in healthy stem cells is likely to have some toxicities. I don’t see a mechanism for SOT to only target cancer cells and not healthy cells.

Large infusions of synthetic RNAs could also spark unwanted immune system reactions.

In addition, some cancer patients receiving SOT may be forgoing other, more established treatments, which is another possible risk. Along those lines, the SOT patient guide (included earlier in this post) suggests that customers should not get certain drugs, some that might be fairly common cancer treatments such as cytotoxic therapies, for a two-week period prior to administration of SOT.

Medical marketing of SOT therapy in the US

With all of these possible risks and uncertainties in mind, let’s circle back to SOT clinical use in people in the US.

Sources sent me lists of dozens of clinics already marketing SOT in the US. I was quickly able to confirm on many of these American firms’ websites that they are indeed selling SOT for clinical use.  There are many such SOT clinics just here in California.

The websites most often make claims about SOT medical use for Lyme disease as well as other infection-related conditions but also cancer. Some clinics claim SOT can eradicate cancer cells (see Google search results above). The specific marketing descriptions on clinic websites are also consistent with the idea, as noted earlier, that SOT is a drug as used within the US.

Naturopaths seem to be selling SOT the most but there are plenty of MDs marketing it too. There are also numerous SOT clinics in other countries so that’s another level of concern.

I’ve included a skeptical video on SOT for Bartonella, which I found quite interesting.

Parallels to unproven stem cell clinic industry

References on SOT RNA therapy

• Supportive Oligonucleotide Therapy (SOT) as an Alternative Treatment Option in Cancer: A Preliminary Study. 
• Supportive Oligonucleotide Therapy (SOT) as a Potential Treatment for Viral Infections and Lyme Disease: Preliminary Results
• Is SOT for Lyme & Tick-borne Infections a Scam?