ALS Untangled®

ALSUntangled® reviews alternative and off label treatments (AOTs), with the goal of helping people with ALS make more informed decisions about them.

Risks (harms that occurred on this treatment)

RCH4

by

RCH4 is an unlicensed, unapproved product reported to “probably slow the progression of your ALS” (6) on a website. The only peer reviewed publication we found on this product is a single abstract which was never presented at a meeting. We have been unable to determine RCH4’s structure or chemical class, and its purported mechanism is one that has never been shown to be useful in treating PALS before. We have been unable to independently verify RCH4’s reported efficacy or even safety. Thus, at this time, we cannot advise PALS to use this product. We hope the proponents of RCH4 will someday present more useful information about their product at a scientific meeting or in a peer reviewed publication.

We believe that regulatory oversight is important for optimizing patient safety on experimental drugs, and that independent peer review and replication are fundamentals of good science. Caution should be exercised around any product being developed and in clinical use without these safeguards and fundamentals in place.

Click here to download the complete review.

Resveratrol

by

Resveratrol is a dietary supplement that likely activates SIRT1 cellular pathways and may alter the gut microbiome. These are interesting mechanisms that may potentially alter the progression of ALS and do confer benefit in animal models of one type of familial ALS; however, to-date, there have been no trials of resveratrol in PALS. Some trials in other populations show frequent gastrointestinal adverse events, including weight loss, and one trial showed a high risk of serious renal toxicity. Given the unknown benefit of resveratrol in PALS and the possible risks, we cannot recommend resveratrol as an ALS treatment at this time. We hope to see well-designed clinical trials of resveratrol and other SIRT1 modulators in the near future.

Click here to download the complete review.

Copper ATSM

by

Copper dysregulation may play a role in ALS progression, particularly for the form caused by SOD1 mutations. Given the complexity of this problem, simple copper supplements are unlikely to be useful to PALS with normal serum copper levels. We do not recommend using these. CuATSM, on the other hand, has more promising potential mechanisms of action, and several positive pre-clinical studies in mutant SOD1 ALS models. There are even a small number of PALS reporting benefits from it, though in our opinion the described benefits are thus far of uncertain clinical significance. At this time, the safety of repeated doses of CuATSM is unknown, as is the optimum daily dose, and it appears to be very expensive. Until trials clarify dosing and safety, as well as effectiveness in patients with and without SOD1 mutations, we do not recommend using CuATSM for ALS.‌‌‌‌

Click here to download the complete review.

GM604

by

At this time ALSUntangled finds no independently verifiable data supporting the efficacy or even the safety of GM604 in patients with ALS. We believe that independent peer review and replication are fundamentals of good science (36,37). Accordingly, we share the FDA’s April 2015 opinion that the data on GM604 in ALS should be released now for

independent peer review (38). If these preliminary data are confirmed to be positive, statistics on the false-positive rate of small trials (29,30) and consensus ALS trial guidelines (35) dictate that they be replicated in a larger, longer duration study before GM604 is deemed effective or even safe for patients with ALS.‌‌

ALSUntangled generally supports the use of expanded access programs during ALS drug development. We believe that these should be reserved for treatments that have at least some independently verifiable safety data. In our opinion, that is not the case with GM604, so we feel that expanded access is premature at this time. When we can independently verify safety data, we hope to see a GM604 group expanded access program that has transparent entry criteria, systematic objective outcome measures, full disclosure of results, and, as suggested by the FDA, allows for a sponsor’s cost recovery but not for profit (39).‌‌‌

Click here to download the complete review.

Endotherapia

by

Endotherapia has a proposed mechanism that hinges on the ability of an isolated laboratory’s immunoblots to identify the cause and specific pathways that are driving ALS progression. In our opinion this ability has never been convincingly demonstrated. While there is a flawed animal study supporting the utility of Endotherapia in rats, such studies rarely translate into useful human treatments (29). The data on Endotherapia in PALS have so many problems that we believe they are uninterpretable. ALSUntangled does not recommend the use of Endotherapia for ALS at this time. A reasonable next step would be a study to validate the utility of the above-described immunoblots, ideally by a group without a potential conflict of interest.

Click here to download the complete review.

Cannabis

by

Cannabis has biological properties including immunomodulation and effects on excitototoxicity that suggest it could be useful in ALS. Evidence from small, non-randomized, unblinded animal studies suggest that it could potentially slow ALS progression, and anecdotal reports suggest that it could ameliorate troubling ALS symptoms. Given all this, ALSUntangled supports further careful study of cannabis and cannabinoids, the active ingredients contained therein. Natural cannabis, as a single agent, provides advantages similar to a multiple drug trial given its numerous mechanisms of action. A possible next step would be a small case series of well-characterized PALS using cannabis at controlled dosages that could potentially be monitored by blood levels of cannabinoids, compared to matched controls, performed in a geographic area where it would be legal.

Mototab

by

Given the lack of demonstrated effectiveness, and the above-documented concerns about product safety and supplier identity and reliability, ALSUntangled does not support the use of mototab

Figure 2. Remarkably similar websites of SPAH comparisons.

for amyotrophic lateral sclerosis or any other motor neuron disease. If Oslo Health Solutions ever con-tacts us with additional useful information on this product we will gladly publish an addendum to this investigation.

NuTech Mediworld

by

Now 26 months old, ALSUntangled (www.alsuntangled. org) investigates alternative and off-label treatment options in ALS using social networking tools. Our twitter and NING memberships continue to grow. To date we have published 10 investigations on 11 different alternative and off-label treatment options, collaborating with Quackwatch (www. quackwatch.org), Patients Like Me (www.patients likeme.com) and ALS Worldwide (www.alsworld wide.org). We now present our investigation of NuTech Mediworld’s ALS treatment regimen which was undertaken at the request of patients with ALS (PALS).

NuTech Mediworld is a ‘stem cell clinic’ in New Delhi, India and is run by Dr. Geeta Shroff. In an effort to obtain information about the clinic, we tried to start with the clinic website (www.nutech mediworld.net), but this site has been down for the entire three months that we have been working on this piece. We made three attempts at contacting Dr. Shroff via email at the address we found on the web (1); unfortunately, we received no responses. We performed a search of the literature using Pub Med; we could not find any articles published by Dr. Shroff. She has apparently applied for patents related to the use of human embryonic stem cells used in a variety of seemingly vague ways to treat more than 70 human diseases including motor neuron disease (2). Blogs, YouTube videos and various interviews with patients with ALS suggest that Dr. Shroff is an ‘infertility expert’, using a cell line derived from a single embryo, and that these are being injected multiple times into the spinal fluid (2). In an interview Dr. Shroff suggested that, as of 2007, she had treated “more than 300” patients and that “almost everybody” had improved (3). In that same interview, it was noted that she was not using “any immunosuppressants or anti-rejection drugs” along with her treatments (3). Beyond this, we have been unable to find any presentation of an actual ALS treatment protocol, or any detailed safety or efficacy data.

We found two PALS who received treatment at Nu tech Mediworld and were also cared for by ALSUntangled affiliated clinicians. The first was a 44-year-old male, diagnosed in early 2010. He started regular follow-ups with an ALS expert only after his trip to NuTech Mediworld in June 2010, so it is not possible to examine validated outcome measures before and after his treatment there. How- ever, he provided a discharge summary from NuTech Mediworld with Dr. Geeta Shroff listed as ‘doctor in charge’. Interestingly, this contains no record of the patient’s prior work-up; furthermore, the only neurological examination states that the patient was ‘conscious, cooperative alert, oriented with time, place’. Thus, it does not appear that any objective confirmation of his ALS diagnosis was made. No consent form was provided with the discharge summary. Some testing was reportedly performed in the clinic. This included a blood count, serum chemistry, ‘Australia Antigen’, HIV, urinalysis, B12, vitamin D level, chest X-ray, EKG, abdominal imaging, echocardiogram, and brain SPECT scan. Under ‘treatment given’ the document merely states ‘patient was given human embryonic stem cell therapy during his stay in this hospital’. His ‘condition during discharge’ was noted to be ‘satisfactory’ with decreased ‘fatigue’, ‘walking, balance better’, increased ‘UE power’. Again, there are no validated measurements documented to confirm these conclusions. The patient reported receiving injections into his back, neck, shoulders and hands. Additionally, he reported receiving ‘three different antibiotics’ for ‘Lyme disease’ under Dr. Shroff. ‘Physiotherapy as advised’ was prescribed.

The second patient was a 36-year-old female, diagnosed in May 2010 and followed by an ALS expert before and after the NuTech Mediworld treatment. A discharge summary was not available on her, but she recalled events similar to the previous patient. These included a lack of neurological examinations, unusual testing including a Lyme test, and unusual adjunctive therapy including antibiotics for Lyme disease (even though her Lyme test was negative). Clinical data appear in Figure 1. Her weight, vital capacity and ALSFRS-R scores all appeared to worsen slowly over the first few months of her disease. Following treatment at NuTech Mediworld in late September 2010, her weight and vital capacity appeared to drop precipitously. Between May and mid-September 2010, her weight was stable and predicted vital capacity changed by only 4%. Between September and mid- February 2011, her weight dropped by 32 pounds, and her predicted vital capacity dropped by 25%. Subjectively this patient felt that her bladder control was improved by her NuTech Mediworld treatment. Her treatment cost $45,000 and was not covered by insurance (4). She did not recall any side-effects.

According to the ALS Worldwide publication ‘A Patient’s Path through the Maze of Stem Cell Transplantation’, Dr. Shroff ‘has no background in stem cells, has never published anything and makes extraordinary claims to have cured more than 100 patients of everything from Alzheimer’s disease to spinal cord injury. In fact, she claims to be able to cure more than twenty different diseases with treatments proven to be bogus. Her credentials are nowhere to be found. Multiple lawsuits against her exist’. This publication classifies NuTech Mediworld under ‘notorious stem cell operations: avoid, shun and ignore their claims’. Indeed, NuTech Mediworld and Dr. Shroff were apparently subject to a governmental inquiry in 2006; the results of that inquiry are not widely known (5).

In summary, ALSUntangled can find little objective information on the technical and safety aspects of NuTech Mediworlds’ stem cell treatment.

The main part of the treatment is alleged to be some type of embryonic cell line being injected into spinal fluid (and possibly other various body parts) without immunosuppressives; to our knowledge it has never been demonstrated that embryonic cell lines are safe, not to mention effective, for ALS when used in this way. We can find no information confirming Dr. Schroffs’ education and training to perform stem cell transplants. We can find no evidence that ALS diagnoses are being appropriately confirmed at NuTech, nor that adequate informed consent is being documented prior to treatment, nor that validated ALS outcomes are measured after treatment. We did find a number of unusual tests being performed there, as well as odd concurrent treatment for seronegative Lyme disease. For the one ALS patient in whom validated outcomes were available, there actually may have been a worsening rate of disease progression following NuTech treatment. We would welcome an opportunity to discuss our findings with Dr. Shroff and review any additional information that she can provide in order to provide as accurate and fair an assessment about NuTech Mediworld Stem cell treatments possible. We invite Dr. Shroff to write a letter to this journal, present her results at an international ALS meeting, or meet with us directly. Unless or until this occurs, ALSUntangled suggests that patients with ALS avoid NuTech Mediworld.