Effectiveness of Treatment for GDD. Current status.

At the present time, I can reflect back on how we are doing with success rate with treatment for GDD, who does well, and where we are still in evolution.

Traditionally with most diseases (eg: trauma, cancers, infections) the sooner you treat, the better the outcome.

Very early on I recognized that this was not the case for patients with recent onset GDD and optimal treatment. The concept is: if Gd is the problem, use the best available method to get the Gd out. Simple concept, and the best available, FDA-approved chelator is DTPA. This is simple test-tube science: it has the highest stability constant for Gd uptake of all available FDA-approved chelators. Is it the absolute best chelator? Almost certainly not, but it is the best available and also extremely good.

But what happens is: GDD recent onset, only treatment is chelation with DTPA, the result is a huge problem, why does it break the rules? The reason is because what is causing the disease is the host immune response, if you do not dampen the host immune response an enormous Flare will result. This was the recognition of the importance of using FRAME drugs concurrently with DTPA. With time as well, the immunological memory diminishes, which means that the individual does not have as violent Flares as time goes along.

Looking at the 3 categories of disease settings and disease severity:

1. Recent onset GDD from a single (occasionally up to 3) GBCA administration, treatment being initiated at 3 months out from GBCA injection to 2 years out, the cure rate (getting > 80% better) approaches 100% with 5 chelation sessions (in some as few as 3 sessions) using Ca-/Zn-DTPA with concurrent FRAME. This was formerly a category of patients that universally did poorly with DTPA chelation alone.

Prior use of other chelators though may complicate the story.

2. The middle category of patients: multiple GBCA injections and no physically apparent disability. The base number of DTPA + FRAME chelations for substantial improvement is 10 sessions. In maybe 75% subjects, they achieve greater than 70% improvement.

3. On the extreme end of the spectrum are those with multiple prior GBCA injections, over a number of years, and are currently physically debilitated. The physical disability must be obvious on inspection. It does not appear that DTPA + FRAME alone is sufficient to achieve 80%+ improvement in any appreciable number of sufferers. We have focused on developing additional therapy to address this issue. Clearly DTPA chelation is still a large part of the treatment... but there is the danger that too many chelations (> 50, maybe > than 30) may create effectively a Gd-independent autoimmune disease. Why does this happen? Every chelation is essentially like a mini-GBCA injection (as I have previously written) so each successive DTPA chelation re-ignites the immunological memory for Gd. If there are too many chelations, without concurrent immune system dampening, it may no longer be necessary for Gd to be present for immune cells to be on constant high alert. With deeply ingrained immunological memory for Gd with physical debility, the combination of DTPA + FRAME will not be sufficient to improve the disease. This is now a principle focus of our development of more advanced immune modulation probably in combination with treatment for chronic nerve disease/ sympathetic dystrophy.. We are not in an optimal state of treatment plan yet.

Summary of treatment:

1. recognize that GDD is present as soon as it occurs, and do not undergo any future GBCA injections. One GBCA injection is like stage 1 cancers, which are generally highly treatable, multiple injections the situation is no longer like stage 1 cancer, but now stage 3 (advanced cancer) and very difficult to treat, and often are no longer curable. Simply not getting another GBCA injection ever again is the principle treatment for all GDD patients, and may be sufficient for many sufferers following just 1 GBCA lifetime injection. If they have had 1 lifetime GBCA exposure and within 3 months, many actually may recover on their own without chelation or other therapy. For this group it is critical to keep in mind - is the patient getting better on their own or secondary to treatment? Incidentally this is the same thought process that must happen following COVID 19 therapy - and actually the majority of diseases of humans (exception being malignancy).

2. after 1 GBCA injection (perhaps up to 3) and development of GDD, and treatment between 3 months - 2 years with Ca-/Zn-DTPA chelation with concurrent FRAME drug immune dampening, the success rate is extremely high with 5 chelation sessions resulting in > 90% of sufferers having > 80% recovery. Note at that point my plan is the individual's own immune system recovers the rest of the way on its own, with some oral supplements and other physical therapies.

To step back and compare at this point: if one considers all medical treatment for all conditions, and what the success rate is with health care, maybe 20% of patients are worse after treatment, 20% are the same, 20% are marginally better, 20% noticeably better, and 20% near cure ( the first quintile). For this group of GDD sufferers our treatment is in this first quintile. Also with just 5 treatments. How many drug therapies require treatment for life? Maybe 30-50% of them. Ours is a 3 month treatment.

3. Many patients presently are in the category of multiple injections over some years, and although in constant suffering, are not frankly physically debilitated. In these the success rate is very good, but at present somewhat unpredictable. Probably 80% get at least moderate improvement, maybe 50% get improvement > 80%.

4. Patients at the extreme, with multiple injections or even single injection with physical debility, and often complicated with time and with multiple other less effective treatments (including DTPA chelation without FRAME). Probably 40% get moderate improvement (60-80% better). with DTPA + FRAME. To date none seem to get >80% better. Hence the importance of more high potency immune, and other systemic, treatments. We are focused on this.

Richard Semelka, MD