The MEND™ protocol for Alzheimer’s disease: Functional medicine on steroids?

A recurring theme of this blog is to shine a light on what I like to call “quackademic medicine.” I didn’t invent the term, but I’ve made it mine. Basically, quackademic medicine is a term that very aptly describes what’s going on in far too many academic medical centers these days, which is the infiltration of pseudoscientific medicine and outright quackery in the form of “complementary and alternative medicine” (CAM). Of course, the more recent term for CAM is now “integrative medicine,” which was coined to imply the “integration” of alternative medicine with science-based medicine as though they are equals. Thus, there are academic medical centers that embrace acupuncture, reiki, and naturopathy, the last of which includes homeopathy as an integral part of its curriculum and skill set.

Among the centers of quackademia, of which there are far too many in existence, George Washington University is among the most egregious when it comes to embracing pure quackery. The last time I discussed GWU, I noted that the Center for Integrative Medicine at the George Washington University Medical Center (GWCIM) offers services that, charitably, be called pure quackery: acupuncture (of course!), chiropractic, craniosacral therapy, infrared light therapies, glutathione infusions, Myers’ Cocktail, naturopathy (again, of course!), reiki, intravenous high dose vitamin C, and genetic profile results that include “customized interpretation of 23andme.com genetic profile results with specific accent on methylation and detoxification profiles.” Some of these are quackery. Some are “rebranding” lifestyle interventions as somehow “alternative” (and therefore much more hip). Some blur the lines between the two, such as “functional medicine,” a branch of CAM that combines “wholistic” medicine with a whole lot of lab tests and supplements to correct abnormal lab values. The Cleveland Clinic is especially enamored of functional medicine.

Now I learn that GWCIM has recently added another questionable treatment to its already expansive list of questionable protocols. No, the protocol to which I’m referring is not homeopathy, craniosacral therapy, or high dose intravenous vitamin C. The kindest way to describe it is experimental, even though it seems to be offered to anyone without a clinical trial. As it is experimental, it is unproven. It’s also based on pretty thin gruel as far as clinical data goes and resembles to me the premature use of 23andme genetic profiles to guide care before we even know what these profiles mean. No, strike that. It reminds me of functional medicine:

Muses Labs announced today that it has partnered with the George Washington Center for Integrative Medicine (GWCIM) to offer the MEND™ Protocol to patients located in Washington, DC. This agreement allows individuals with pre- and early-symptomatic cognitive decline, as well as mild Alzheimer’s disease patients, to benefit from the MEND Protocol via the Center’s Mental Health program operated in collaboration with the George Washington University Memory Clinic.

The MEND Protocol is a data driven, technology enabled, personalized methodology to correctly identify and simultaneously treat the dozens of pathology drivers of age-related cognitive decline. The MEND Protocol is designed to help patients who are beginning to have symptoms of age-related cognitive decline, those with a family history of dementia and patients with mild Alzheimer’s disease. The Protocol recommends optimal medical interventions personalized for each patient and has the potential to improve memory and cognitive function. The MEND Protocol is an emerging methodology that reflects a new approach to addressing complex diseases.

The MEND™ Protocol is a treatment for Alzheimer’s disease marketed by Muses Labs. I always become very suspicious when I see marketing materials that make claims like this:

MEND™ Protocol simultaneously applies multiple medications and lifestyle changes in a highly-personalized manner to attempt to halt and reverse mild cognitive impairment (MCI) and early stage Alzheimer’s disease. MEND Protocol utilizes existing FDA-approved drugs, supplements, lifestyle changes, and medical markers and tests in a novel manner. Personalization of the protocol depends upon an individual’s genome, medical test results, comorbidities, current medications, medical history, and other inputs.

MEND Protocol is designed to address the active underlying pathways for Alzheimer’s disease including metabolic issues, toxicity, inflammation, and mitochondrial damage. Due to the complexity of the personalization process, the Protocol is realized via health management software. The algorithms are able to incorporate logic to process a wide range of data on an individual’s health status and recommend specific interventions matched to the etiology of an individual. The recommendations are different for each individual and change over time.

Ah, yes, “personalized” medicine and a “personalized” protocol. Muses Labs claim to use these factors to design a personalized treatment for MCI due to early stage Alzheimers:

Based on the recognized causes of cognitive decline, the MEND Protocol collects individual patient biometric and behavioral data, including:

  • Genome
  • Bio-specimen data
  • Medical history
  • Demographics
  • Medications
  • Patient lifestyle
  • Cognitive ability

The MEND Personalized Treatment Plan is provided to both the physician and the patient, so they can review the results together. The physician prescribes the treatment plan as appropriate. Patients are periodically retested and the treatment plan is updated over time.

You know, this protocol smells of questionable science. My skeptical antennae start really twitching when I read things like “toxicity,” “inflammation,” and “mitochondrial damage.” It sounds very much to me like “autism biomed” coupled with an appeal to genomics and computer algorithms. They start twitching especially hard when I see images like these on a website:

Muses Labs

Yes, its’ a scientist in a white lab coat apparently manipulating a DNA double helix with his hand, complete with a white light that makes it look as though he’s shooting energy from his fingers. OK, it’s not quite that blatant, but it’s close. Star Trek fans might remember a term frequently used to describe some of the scientific discussions that occurred on the show, namely “technobabble.” Basically, technobabble consists of impressive and scientific-sounding jargon that, when examined more carefully, turns out to be basically meaningless.

This next part of the description of the MEND protocol might not be technobabble, but it is pure woo babble. Its very name (metabolic enhancement for neurodegeneration, abbreviated MEND) tells me that. So does this next bit:

The analysis algorithm recommends both pharmacological and non-pharmacological components. For example, if synaptic reconstruction and maintenance is needed, then multiple biological mechanisms may require normalization, enhancement, or administration. Examples of these underlying biological mechanisms include: periodically activating autophagy, blocking prionic tau amplification, increasing beta-amyloid clearance, inhibiting beta-amyloid oligomerization, minimizing inflammation, normalizing neurotrophic factors, reducing ApoE Ɛ4- mediated signals, reducing stress, reducing tau phosphorylation, restoring cholinergic neuro- transmission, and reversing memory loss. Assessing the status of these biological mechanisms involves quantifying and observing hormonal balance, citicoline, C-reactive protein and other inflammation-related markers, diet, exercise, homocysteine, omega-3 acids, sleep, and so on. Interventions targeting specific biological mechanisms are then prioritized and prescribed to optimize key biological mechanisms. Medication doses are specified to an individual’s needs. Individuals are re-tested periodically and the protocol is updated as necessary.

What the hell does this even mean?

Whenever I see claims like this, my first instinct is to go to PubMed. At the very least, I expect to find a list of publications on the company website. So, before going to PubMed, I perused the Muses Labs website. All I could find was one publication. Before I get to that publication, though, let me just take a look at some things I found using the almighty Google search. I can’t help but note that all the articles I found using Google mentioned the very same single publication.

As you probably know, Alzheimer’s disease is a form of dementia, of cognitive decline, related to aging. It isn’t (yet) known what causes it. It’s known that Alzheimer’s disease is a chronic neurodegenerative disease. It’s progressive and relentless and the cause of up to 70% of cases of age-related dementia. The cause of the disease is not well understood at all. It is known that Alzheimer’s patients tend to have amyloid plaques (amyloid is a protein) and neurofibrillary tangles in the brain. Currently there are no treatments that stop or reverse its progression, although some can temporarily reverse its symptoms. It’s a horrible, horrible disease, one that I can’t help but fear as I get older. When I have a lapse in memory, I have a tendency to joke about “early onset Alzheimer’s,” but it’s no joke at all. Alzheimer’s dementia is just about the worst fate I can imagine.

Muses Labs itself touts its approach thusly:

The approach we’re employing relies upon advanced software and big-data analytics, and incorporates decades of medical research. Muses Labs offers a service that utilizes the Internet and information technology innovations to make the Protocol practical and accessible to individuals with cognitive decline around the world.

Elsewhere, the company is described thusly:

The company says this approach to Alzheimer’s disease (AD) is based on the molecular biology of the brain and the bodily systems that support it. Decades of scientific research from around the globe are brought together and incorporated into MEND. Muses Labs combines medical expertise with software algorithms. Its algorithms figure out the optimal personalized therapy for an individual, and enables their physician to prescribe the therapy. Muses Labs software then motivates an individual’s adherence to the therapy it recommends.

All of this sounds all very nice and impressive, and there are indeed legitimate scientists on the Muses Labs editorial board, although there is also Dr. Mikhail Kogan, who just so happens to be the Medical Director and the Integrative Medicine Fellowship Director at the George Washington Center for Integrative Medicine, Washington DC. Not surprisingly, he also does geriatrics and embraces functional medicine. Come to think of it, this whole Muses Lab approach reeks of functional medicine, which I like to characterize as “making it up as you go along,” because of its reliance on lots of lab tests whose interpretation is questionable. In this case, we appear to be seeing functional medicine expanding into genomics.

Still, as many red flags as I see in the press releases and Muses Labs literature, it is always possible that the company is on to something. It’s not incorrect when it says that Alzheimer’s disease is very complicated, nor is it incorrect in its assessments of the current “state of the art” that single agent therepeutics have largely failed to reverse cognitive decline. However, it does not follow from that that the MEND protocol works. We’ve been using systems biology approaches to try to develop better treatments for various diseases for at least a decade now, and, in cancer at least, the results have been mixed. There was a lot of hype and hope at first, but it wasn’t long before that hype and hope ran straight into the wall of the implacable biology of the disease. So what’s the evidence for the MENDS protocol?

So let’s take a look at the publication that Muses Labs touts as evidence that its protocol is so promising as a treatment for early Alzheimer’s disease? Given that it’s the only study. It’s also a single-author paper, which is pretty unusual for any sort of case series or clinical trial. I know nothing about the author, Dale E. Bredesen, other than that he is affiliated with the Buck Institute for Research on Aging and UCLA’s Mary S. Easton Center for Alzheimer’s Disease Research. It’s obviously a pilot study; in fact, it’s a small case series of ten patients treated with the MEND protocol.

This case series was immensely unsatisfying to read. It’s open access; so you can read it for yourself if you don’t believe me. I wanted to know more. I wanted to know just what the heck the MENDS protocol entailed. Unlike most papers reporting the results of case series or clinical trials that I read, this paper was very thin on the details. For example, this table describes it (click to embiggen):

The MEND™ protocol: Sure looks impressive and science-y, but it it either?

The MEND™ protocol: Sure looks impressive and science-y, but it it either?

Patient #1 is a 67 year old woman with two years of progressive memory loss whose mother had developed progressive memory loss at roughly the same age, become demented, and ended up in a nursing home, not dying until she was in her early 80s. This was the regimen she was placed on:

As noted above, and following an extended discussion of the components of the therapeutic program, the patient began on some but not all of the system: (1) she eliminated all simple carbohydrates, leading to a weight loss of 20 pounds; (2) she eliminated gluten and processed food from her diet, and increased vegetables, fruits, and non-farmed fish; (3) in order to reduce stress, she began yoga, and ultimately became a yoga instructor; (4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day; [5] she took melatonin 0.5mg po qhs; (6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin 1mg each day; (8) she took vitamin D3 2000IU each day; (9) she took fish oil 2000mg each day; (10) she took CoQ10 200mg each day; (11) she optimized her oral hygiene using an electric flosser and electric toothbrush; (12) following discussion with her primary care provider, she reinstated HRT (hormone replacement therapy) that had been discontinued following the WHI report in 2002; (13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; (14) she exercised for a minimum of 30 minutes, 4-6 days per week.

How we get from “systems biology” to yoga, exercise, weight loss, enough sleep, and a better diet is unclear. You don’t really need systems biology to suggest that these interventions will at least improve health and might slow cognitive decline. As for going “gluten-free”? On what rationale was that intervention based? I have the same questions regarding fasting and the vitamins. Basically, reading the relatively vague description of the MEND protocol provided here, I see nothing that requires all that fancy systems biology and those computer algorithms touted by Muses Labs. How “data-drive” and “big data” do you have to be to come up with this protocol?

Another failing of this writeup should be obvious to anyone who routinely reads (and especially to anyone who participates in) clinical trials. What were the objective outcomes? Even in a case series, there are usually some objective outcomes examined. For example, did they do various tests of cognitive function before and after, in order to determine if there was any objective improvement. How was the diagnosis of cognitive decline nailed down. Of the three (out of ten) patients described, patient #2 is the only one whose workup for Alzheimer’s disease was described in anything resembling in depth, and there is no report of any followup tests, just the patient and wife’s reports of his improvement. Basically, nine of ten patients reportedly demonstrated “objective or subjective” improvement, and six were able to go back to work. That’s nice, but where are the results of the full dementia evaluations, complete with standardized cognitive assessment examinations before and after the MEND protocol intervention? This case series really needs some meat on its bones before it will persuade me that there might be anything to this protocol. As it is, it sounds like one of any number of studies and case series published in CAM journals: Long on description, short on concrete reporting and controls.

As a pilot study, this sounds on its surface mildly promising, although it is really hard to tell given the lack of description of anything resembling something a clinical scientist would want to know to judge if further study is needed. Maybe it is. Maybe it isn’t. Another disturbing thing about this paper is that there is no mention of institutional review board approval, making me wonder if this was IRB-approved. Even a retrospective case series needs IRB approval, at least before publication, and this doesn’t seem to have it. Searches of Clincaltrials.gov failed to find registered clinical trials of the MEND protocol.

Maybe this protocol is worthy of further study. Maybe it’s not. I can’t tell for sure if it is based just on this paper and Muses Labs hype, both of which have enough red flags in them to make me think that the MEND protocol is nothing more than functional medicine on steroids. Whatever the case, however, I can be convinced, but not by this thin gruel. If Muses Labs and, presumably, GWCIM, are ever going to find out whether its protocol works to halt or reverse early cognitive decline in age-related dementia caused by Alzheimer’s disease, they should stop putting the cart before the horse and treating patients with an unproven protocol outside of the context of an IRB-approved clinical trial protocol. They should do the hard work it takes, get a protocol IRB-approved, and do the clinical trial before offering the MEND protocol to just anyone off the street suffering from early Alzheimer’s. That’s how you find out if a new protocol works. The MEND protocol might not be quackademic medicine, but how it’s being sold sure feels like it.

Oh, and try not to fetishize computer algorithms and systems biology so much. Nothing in the MEND protocol that I can see depends on either.