SOT therapy

What is SOT therapy?

Supportive Oligonucleotide Therapy (SOT) is a process that enables the RGCC lab to identify the specific gene sequences of different targets such as cancer, Lyme, and various viruses and design a specific oligonucleotide therapy. The SOT is uniquely tailored to each patient’s needs. It is a small oligonucleotide which is complementary to a specific sequence of individual genes which are related to anti-apoptotic signals inside cancer cells, or genes essential for microorganisms and viruses’ survival or metabolism. Apoptosis is another word for programmed cell death. In other words, the SOT molecule has a potent ability to block specific mRNA with a very high rate of specificity, therefore expression of desired gene is inhibited.

How does SOT therapy work?

A patient’s blood is sent to the RGCC lab where the scientists identify the appropriate gene that needs to be silenced. Once they detect the potential
genes for targeting, they validate these targets both in silico and in vitro. The validation of the target ensures the highest specificity and does not interfere with any other targets. Once the different target genes have been validated, then the most appropriate gene is selected and the laboratory creates an oligonucleotide, complementary to the mRNA for a specific region of this gene. This in turn creates an antisense therapy. These molecules are delivered to the clinic where the patient receives the one dose IV treatment. Once the patient receives the SOT molecules, they are at work 24 hours a day, seven days a week for up to six months, inhibiting the appropriate gene.

Go here for an informative video on SOT:
https://www.youtube.com/watch?v=MgVuSSoHrJg

Is there more information on the full SOT process?

Below is an article which describes exactly how the whole process of ADME is taking place, both for Absorption, Distribution, Metabolism, Excretion.

https://www.tandfonline.com/doi/full/10.1080/17425255.2021.1992382

What is the goal of SOT therapy?

To inhibit the expression of proteins which are essential for the cell metabolism and/or survival.

What kind of cancers can be treated with SOT therapy?

• Solid tumors
• Hematologic malignancies

What kind of cancers should not be a consideration for SOT therapy?

• Central Nervous System Cancers (CNS)

What kind of viruses can be treated with SOT therapy?

• HHV1/HSV1 – (Human Simplex Virus – Oral-Facial)
• HHV2/HSV2 - Herpes Simplex Virus – Genital)
• HHV6 (A & B) – Human Herpes Virus – 6
• CMV – (Cytomegalovirus)
• Coxsackie Virus (Type A & B)
• VZV - Varicella Zoster (shingles)
• EBV - Epstein-Barr Virus
• HPV- (16/18) - Human Papilloma Virus
• HPV- (6/11) - Human Papilloma Virus
• HBV - Hepatitis B Virus,
• HCV - Hepatitis C Virus
• HIV - Human Immunodeficiency Virus
• HTLV1 – Human T-Cell Lymphotropic Virus

What species of Lyme and coinfections can be treated with SOT therapy?

At what cancer stage should a patient consider SOT therapy?

Any stage is appropriate; however, careful evaluation of the patient is important. Patients with a large tumor burden (single or multiple tumors over 5 cm total) are at risk for Tumor Lysis Syndrome.

Is SOT therapy safe?

SOT therapy has been assessed in thousands of studies for their safety. Toward investigating this, here are some studies of interest:

https://doi.org/10.1002/(SICI)1097-4652(199911)181:2%3C251::AID-JCP7%3E3.0.CO;2-D

https://pubs.rsc.org/en/content/articlehtml/2020/ra/d0ra04978f

https://www.annualreviews.org/doi/abs/10.1146/annurev-med-041217-010829

https://www.tandfonline.com/doi/full/10.1080/17425255.2021.1992382#

https://www.nature.com/articles/nrneurol.2017.148

https://wires.onlinelibrary.wiley.com/doi/abs/10.1002/wrna.1594

https://www.mdpi.com/612152

https://journals.sagepub.com/doi/abs/10.1177/1756286418776932

https://www.sciencedirect.com/science/article/abs/pii/S1359644617300430

Are there any contraindications or disqualifications for the SOT therapy?

• Pregnancy or breast feeding – must wait 6 months
• Recent blood transfusion – must wait 120 days
• Recent cytotoxic chemotherapy and/or radiotherapy – must wait 14-21 days
• Radioactive Seed Therapy (permanent contraindication for Cancer only)
• Delta T. Cell Therapy (GDTC) (permanent contraindication for Cancer only)
• Children under the age of 11 for cancer
• Children under the age of 5 for viral or Lyme

Note: See full list of substances/therapies/treatments and associated time lines below under “What Needs to be Avoided for SOT therapy”

Can SOT therapy be done on children?

• For Lyme/Viral: SOT for Lyme for children over the age of 4 (Reason: the sequence of interest has no overlapping parts with human genome)
• For Cancer: SOT For malignancies for children over the age of 10 is at the discretion of the Physician. An evaluation of the thymus gland to verify it is atrophic is recommended for a child under the age of 10. (Reason: An overlapping of 60% of the SOT sequence may generate heterodimers between mRNA and SOT which has no consequence in adults, but in children when the clones of auto-epitopes have not been locked then there is a small (but not zero) possibility to create an autoimmune clone of B cells that may generate an autoimmune condition in the future. It’s important that the physician and the parents be made aware of this potential risk.

Are there any risks with the SOT therapy with cancer?

• Tumor Lysis Syndrome – TLS (fever, local edema, accumulation of fluid in the area of the tumor, etc) is a potential risk with SOT and patients should be properly evaluated prior to ordering the therapy. TLS occurs mainly with large or numerous tumors. It is important that physicians are educated on how to treat TLS if administering it to cancer patients at risk for this.
• Even if the tumor load is under 5 cm and TLS is not a concern, the lysis of tumors can cause discomfort depending on the location of the tumors (bone, lymph nodes, rectal, etc.). Patients should be warned of this and a pain management plan should be in place.

Are there any possible adverse reactions with SOT therapy?

While SOT is well tolerated, when dealing with living pathogens in a human body there are potential side effects even with a gene silencing therapy like SOT.

Some of the common side effects we’ve seen are:

• Headaches
• Increased fatigue
• Flu like symptoms
• In Cancer - pain at surgical site can occur
• In Cancer - TLS syndrome mainly with large or numerous tumors
• In Lyme or viral - Herxheimer reactions can occur
• In Lyme or viral - co-infections can flare

Will one SOT therapy cover multiple infections?

• The SOT targets only a specific region of a gene. If a patient has multiple active infections, then multiple SOT treatments will be needed. One for each infection since each target has its own unique DNA sequence

Can SOT therapy be given a half dose?

• It is recommended to administer the SOT at full dose, however when deemed necessary by the healthcare provider, it can be split into half doses
• The second half must be stored -17 to -23 C and given within 21 days
• If the second half needs to be given over 21 days, it must be stored at -80 C
• For cancer only, the SOT can be ordered as “less aggressive” this will target the same gene but a different region than a regular SOT allowing for die off to occur at a slower rate.

What is the cost of SOT therapy?

• 1300 Euro for each SOT therapy created What is included in the cost of SOT?
• The SOT therapy only (does not include pre medications or infusion materials)

What kind of pre-tests are required for SOT therapy for Cancer?

• Positive RGCC test result confirming presence of CTCs
• Must be within six (6) months

What kind of pre-tests are required for SOT therapy for Viral or Lyme?

• Positive test result confirming presence of the targeted pathogen
• Test result can be PCR or antibody result
• Test result must be serum-based results (urine will be accepted)
• Pathology results will not be accepted for a SOT order
• IND or NPS will be accepted but these results run a higher risk of the pathogen not being found and a cancellation fee being incurred.
• Test result must be within six (6) months (date of blood draw)
• Test must be from a reputable lab

How much blood is required for SOT therapy?

• Send 15 – 30 ml whole blood in RGCC vial
• For viral or Lyme only - If ordering two to three SOTs, send one full vial of 30 ml
• Cancer SOTs should always be done with a fresh blood specimen since the targeting can change based on the lab’s analysis
• Do not fill over the top of the label on the vial or you risk the chance of the vial leaking

Note: Cancer SOTs should always be done with a fresh blood specimen since the targeting can change based on the lab’s analysis

How does SOT therapy need to be stored?

• SOT in the dried form can be stored for up to six months if kept at room temperature and protected from light. Storage in a drawer or in a climate controlled environment is acceptable.
• SOT after reconstitution can be stored in a freezer at -17 to -23 C for up to 21 days
• SOT that need to be stored for longer than 21 days needs to be stored at -80 C

How many SOT therapies can be given in a year?

• Cancer - Maximum of four (4) total in a 12-month period (must be spaced at a minimum of three months apart)
• Viral or Lyme - Maximum of nine (9) total in a 12-month period (must be spaced a minimum of (7) days apart)
• SOTs for the same target must be spaced at a minimum of (3) three months apart and you must provide updated test result that shows the pathogen is still present before a repeat for the same pathogen will be allowed.

Note: SOTs work for a long time and can accumulate in the body and build up

How close together can SOT therapies be given for multiple targets?

• For virus or Lyme – There is a minimum of seven (7) days between two different SOTs.
• For cancer – Three (3) to four (4) months apart with a maximum of four (4) in a 12-month period

Can other therapies be given on the same day as SOT therapy?

• No other therapies are allowed on the same day as a SOT administration. There is no therapy that will make the SOT work better, however, you can interfere with it!

What needs to be avoided before SOT therapy?

• For Cancer (Apoptosis Inducer): The patient must be off cytotoxic therapies and free radical producing substances 7-21 days prior to the blood draw for the SOT and again 7-21 days prior to the actual administration of the SOT therapy. Some therapies require a longer time frame. See below for details.
• REASON: The breakdown of the CTC caused by these substances creates debris that interferes with the therapy’s ability to find its target. Allowing time for the body to clear the debris will increase the effectiveness of the therapy.
  • Natural Cytotoxic Substances (IV Substances): (Includes Vitamin C, Ozone, H202, Colloidal Silver, Artesunate, Curcumin, etc.) at least 14 days
  •  Natural Substances (oral supplements): cytotoxic substances (per patient’s Onconomics Plus results) at least 14 days
  • Off label medications – such as Ivermectin, FenBen and Itraconazole: 21 days
  • Chemotherapy (non-platinum derivative): at least 14 days
  • Chemotherapy (platinum derivative): at least 21 days
  • MOAB or SMW drugs 14 days
  • Blood Transfusions: at least 120 days
  • Radiation: at least 14 days
  • Scan with Contrast: at least 14 days
  • Surgery (simple/routine): at least 7-10 days
  • Surgery (brain or extensive): minimum of 30 days based on time of recovery. Could be longer if slow recovery or if the person had some type of adverse reaction. Must be evaluated on a case-by-case basis
  • Fever: at least 14 days
  • Hyperthermia (local/concentrated/microwave ablation): at least 30 days due to increase in cellular debris released into blood stream
  • Hyperthermia (generalized/systemic): no waiting
  • Cryoablation: no waiting
  • PEMF – at least 7 days
  • Rife – at least 7 days
  • Hyperbaric Oxygen Therapy - at least 7 days
  • Hormone Suppression Therapy – take half life and times it by 5 (Ex. 5 hours x 5 = 1 day)
  • Radioactive Seeds: Patients are permanently not eligible for therapy due to the prolonged and undetermined time of the radiation exposure
  • Gamma Delta T Cell Therapy (GDTC): Patients are permanently not eligible for therapy due to the potential interaction with RGCC therapies
• For Virus/Lyme (V. Antagonist): The patient must be off all therapies for 14 days prior to the blood draw for the SOT and again 14 days prior to the actual administration of the SOT therapy. This includes:
  • Antibiotics (oral or IV)
  • Antiviral medications (oral or IV)
  • Anti-parasitic medications (oral or IV)
  • Methylene Blue
  • Rife
  • Scan with contrast
  • Vitamin C (IV)
  • Colloidal Silver (oral or IV)
  • H2O2 IV
  • Ozone (IV)
  • Natural Substances (ALL oral supplements that are trying to kill or
    suppress the same target as the SOT)

What needs to be avoided after SOT therapy?

• For Cancer (Apoptosis): All therapies may be resumed (as outlined above) 14 days after administration
  • IV-C can be resumed after 7 days
• For Virus/Lyme (V. Antagonist): All therapies may be resumed (as outlined above) 7 days after administration
• Major blood draws - it is recommended to wait at least 8 days after SOT infusion before any major blood draws are done

What does not have to be avoided after SOT therapy?

• Biofilm busters
• Oral detox supplements such as glutathione
• Cytokine reducers
• Binders
• Routine supplements like multivitamins, vitamin D, probiotics, etc.
• Foot baths

Wait at least 7 days after the SOT infusion to resume:

• PEMF, Rife or HBOT

What follow-up tests are required for SOT therapy?

• For Cancer: Oncotrace or Oncotrail are recommended every 3-4 months after the administration of the SOT to evaluate the status of the CTC and the immunophenotypes.
• For Viral or Lyme: The same lab that was used to order the SOT should be used to evaluate the status of the pathogen 4-6 months after the SOT administration.

What kind of outcome can be expected with the SOT therapy?

• Cancer Patients: Approximately 78% of cases had a positive clinical outcome (Complete response or Partial response or Stable disease)
• Virus Infected Patients: The positive clinical outcome reached 91%
• Lyme Disease: Approximately 95% of cases had a positive clinical outcome (percentages include Borrelia, Bartonella and Babesia)

Important: Percentages provided above are in-lab numbers only. The wording "Positive Clinical Outcome," which most define as a “success rate” is actually defined by the lab as a complete or partial response, or stabilization of the disease. This means "success" is any positive response, not eradication, although a complete response for some will mean eradication for others, it may mean the disease doesn't progress or get any worse. This also means the disease may not progress, but the patient's cancer or viral/Lyme load and symptoms may not get any better.

What pre-medications are required for the SOT therapy?

• Mandatory: 4 mg dexamethasone I.V. in a 20-50 ml rapid drip saline solution or slow bolus push in order to counteract the possibility of extravasation of the IV application by stabilizing the veins lumen and allowing more normal distribution of the therapy.
• Optional but highly recommended: IV H2 inhibitors: (Famotidine, Cimetidine, Nizatidine) given at least 60 min before IV. The reason for the H2 blocker is to decrease any chance of headache, nausea, vomiting, and diarrhea. This is rare but very unsettling if it happens.
• Optional: Acetaminophen 500mg of (Tylenol) P.O. and continue every 8 hours for three days if needed

Transferring/shipping a SOT to another clinic

• An SOT can only be sent for infusion to another RGCC registered clinic that has been certified in SOT. Please confirm this is the case before transferring a SOT for infusion.
• When transferring a SOT to another RGCC registered clinic, we highly recommend a patient complete a Release of Records (ROR) form. There is usually a line for “other”. This is where you would indicate a transfer of the SOT.
• The SOT should be sent to the other clinic via courier service (FedEx, UPS, etc.) and insured, when possible. Please note that RGCC will not cover the cost of transfer.
• NEVER send an SOT therapy directly to the patient. The ROR and use of a courier ensure the chain of custody is maintained so all parties can be protected legally and remain confident the therapy was not contaminated in any way due to mishandling. Sending of an SOT directly to a patient may result in disciplinary action.

What materials will be needed to administer SOT?

• NS 250 ml bag
• IV Tubing
• Injection Plug with Cap
• 22 G IV Catheter
• Extension Tubing Set
• (3) 3 ml syringes (one for 1 ml sterile water, two for drawing up pre-meds)
• 10 ml syringe Label this syringe: Patient name, SOT therapy #)
• 20 ml syringes -pre-meds will be added - Label dexamethasone and famotidine)
• 60 ml syringe (to draw off NS waste from 250 ml bag)
• 10 ml NS IV Flush syringes (1 for after each pre-med and 2 for after SOT)
• 20 G 1 ½” needles (for 2 pre-med syringes, SOT syringe)
• 20 G 1” needles (for NS flushes)
• 16 G needle (for 60 ml syringe)
• Vented Vial Access Spike (for IV bag)
• Famotidine vial (unless patient is taking it PO)
• Dexamethasone vial

How to administer the SOT therapy

1. Vial Inspection:
   • Upon receipt of the SOT, you will need to cross-reference the number on the SOT container to your patient’s name. This information is
     included in the confirmation email you received from the lab titled “Therapies List + AWB”. There will not be a name on the actual SOT container so this is important.
   • Inspect immediately upon receiving. SOT is sterile, freeze dried-lyophilized synthetic oligonucleotides and can be stored at ambient room temperature and out of direct light for up to six (6) months if never opened.
   • The vial top should be wrapped with a sealed tamper proof tape.
   • The crystal/powder is very tiny and should be clear or white only. Your clinic may want to obtain a strong magnifying glass for this purpose. If the crystals are other than clear or white, do not administer the SOT, the vial has been compromised. Contact RGCC for a replacement.
   • The SOT are freeze dried, but do not expect a powder form. The SOT is actually closer to a tiny crystal (it can be confused with a drop sometimes) so if you see a small, clear and gel like drop at the bottom of the vial that is normal. With a gentle swirling, the crystal should remain in the initial position, while a true humidity drop will move. Additionally, if you are not able to easily see through the vial then that is true humidity. Do not administer the SOT. Contact RGCC for a replacement.
   • If there are foreign bodies observed after reconstitution (wait at least 10 minutes after reconstitution, true foreign bodies will not dissolve), DO NOT administer the SOT. Contact RGCC for a replacement.
   • If any of the above occurs, please take a picture and email to us at: info@rgcc-international-northamerica.com immediately. They will advise you on what actions to take.
2. SOT Preparation:
   When administering full SOT dose:
   • Open the correct patient numbered vial
   • Dissolve the tiny amount of powder/crystals by adding 1 ml of sterile water to the SOT vial. Do not use saline to dissolve the crystals
   • Close the screw cap, vortex (swirl) the vial gently until the solution becomes clear with no remaining precipitant – Do not shake or use sonication to mix
   • Draw 9 ml of normal saline in a 10ml syringe
   • Draw up the 1 ml of reconstituted SOT into the 9 ml of normal saline into the syringe
   • Tilt back and forth gently to mix
   • The SOT is now reconstituted and ready to be infused When administering half SOT dose (50% protocol):
   • Open the correct patient numbered vial
   • Dissolve the tiny amount of powder/crystals in 1 ml of sterile water for injection. Do not use saline to dissolve the crystals
   • Close the screw cap, swirl the vial gently until the solution becomes clear with no remaining precipitant
   • Draw 9 ml of normal saline in a 10ml syringe
   • Draw the 1 ml of reconstituted SOT into the 9 ml of normal saline into the syringe
   • Tilt back and forth gently to mix
   • The SOT is now ready to be infused
   • Use a marker and mark the 5 ml spot on the syringe
   • Administer the first half (5 ml) of the reconstituted SOT
   • Transfer the remaining 5 ml of reconstituted SOT solution into a cryo vial (this is not provided by the lab).
   • Do not freeze in the syringe to avoid repeated freeze/thaw cycles since it could destroy the SOT molecules
   • Place the remaining 5 ml into the freezer immediately between -17 and -23 degrees (the colder the better). The SOT can be stored at this temperature for a maximum of 21 days.
   • If planning to infuse the second half longer than 21 days, it must be stored at -80° (it is then stable for up to 6 months). Note: if splitting the doses into more than just half, split the doses and freeze them individually in cryo vials. Once again, do not freeze in the syringe.
   • RGCC does not recommend split doses, so this option is at the discretion of the RGCC provider
   • When ready to use the second ½ dose, warm the sealed SOT vial rapidly to 98°F (37°C) by gently rubbing between your hands. Do not heat!
   • The SOT is now ready to be infused
3. SOT Infusion:
   Pre-medications: To minimize any possible allergic reaction, RGCC recommends administering:
   • Mandatory: Dexamethasone 4 mg diluted in 0.9% Sodium Chloride 20 -50 ml bag right before administering the SOT or can be administered as a slow push.
   • Recommended: A H2 Blocker (Famotidine, Cimetidine, Nizatidine) as well as Acetaminophen are recommended but are not mandatory. However, they are routinely administered to decrease any chance of headache, nausea, vomiting or diarrhea from occurring.
   • Famotidine 20 mg (or other as outlined above) diluted in 20 ml syringe. (Note: If giving orally, must be given six hours before the SOT is administered)
   • Acetaminophen 500mg of (Tylenol) P.O. and continue every 8 hours for three days if needed

SOT Infusion Process:

1. Place an IV catheter using standard techniques and verify a good flow
2. Start with a minimum of a 50 – 100 ml bag of saline (larger bag is acceptable)
3. Infuse Famotidine as a slow push
4. Infuse Dexamethasone as a rapid drip or in slow bolus push
5. Administer the SOT preparation (1/2 {5 ml} dose or {10ml} full dose) as a slow push at approx. 1 ml per 5 seconds (let the saline solution run a few seconds in between the 1ml slow push) through the IV route
6. After SOT has been infused, flush the IV access with 20ml of normal saline solution
7. Monitor the patient for possible adverse reaction for the next 45-60 minutes
8. Remove IV catheter following standard procedures

FAQ for SOT therapy

Q: What method are you using to stabilize the oligonucleotides to prevent degradation?

A: Phosphorothioate is the closest to the type of modification used by RGCC

Q: What method are you using to ensure uptake of the oligonucleotides into the various germs I treat in Lyme disease like borrelia, bartonella, babesia etc. Do you have any studies showing that your uptake methodology works?

A: The method is known already and assessed for uptake due to elongation on the 5- ends of the oligo, but we are not going to reveal the sequence and as for the uptake the statistics on cases will reveal the clinical activity of it.

Q: What is your target mRNA for each of the various germs? Which mRNA are you trying to block, what does this mRNA control?

A: We are not going to reveal

Q: Why do you need the patient’s blood, if you already know the target mRNA for each germ?

A: You will be surprised how many patients do not have the correct knowledge of the strain that causes the disease)

Q: How do you know which germs to target?

A: PaldiSPOT detects the germ and strain of Lyme diseases with associated strains

Q: Are there any safety studies for SOTs?

A: The ODNS have been assessed in thousands of studies for their safety.

Q: How are you avoiding the United States Food and Drug Administration labeling this as a Drug subject to their regulations and oversight.

A: Since the sequence differs from patient to patient they cannot be classified as typical drugs, they are under advance therapies for single patient use: See below links:

https://www.ema.europa.eu/en/documents/other/european-commission-dg-health-f
ood-safety-european-medicines-agency-action-plan-advanced-therapy_en-0.pdf
and
https://www.ema.europa.eu/en/human-regulatory/overview/advanced-therapy-medi
cinal-products-overview#action-plan-on-atmps-section