From Gene Therapy to the Bredeson Protocol

AFAIK Dispatch #10

Alzheimer’s Families for Action, Innovation and Knowledge

Feature Note — Bredeson Protocol

When communicating about AFAIK and its concerns, I occasionally get responses from holistic health devotees about the Bredeson Protocol. While I am actually sympathetic to holistic medicine, particularly in areas where traditional medicine has been challenged, I am skeptical of Bredeson insofar as it smacks of “BigAlzheimer’s” bromides about exercise and doing crossword puzzles.

But there is a recent clinical trial showing improvement in cognition (not just slowing of decline) in 84% of patients with Alzheimer’s or pre-Alzheimer’s. The protocol includes:

- Diet was a plant-rich, high-fiber (soluble and insoluble), mildly ketogenic diet

- Exercise, both aerobic and strength training, was encouraged for at least 45 minutes per day

- Sleep hygiene was supported to ensure 7–8 hours of quality sleep per night

- Stress management included biofeedback and heart-rate variability training with a HeartMath Inner Balance for IOS device

- Brain training was carried out using BrainHQ, a digital therapeutic with 29 cognitive exercises

- For those patients with suboptimal hormonal status, bio-identical hormone replacement and appropriate supplements

- For those with gastrointestinal hyperpermeability, infections, inflammation, or impaired absorption and digestion, gut healing with dietary restriction, gut-healing nutrients, and digestive enzyme support

- For those with evidence of systemic inflammation, pro-resolving mediators and anti-inflammatory herbal supplements

- Infectious agents associated with cognitive decline or systemic inflammation were identified and treated, e.g., Herpes simplex

- For those with toxicity associated with metals, targeted detoxification was undertaken with binding agents

So, while I am skeptical so far of pharma’ “pill a day” solution to our woes, this seems both highly involved, hard to replicate, and lots of individual exception. So I’m still skeptical of this particular approach, but as with my support of neurostimulation, maybe there could be more research in Bredeson’s direction.

Beginning this month, I will be organizing dispatches by updates in recurring topics.

Gene Therapy Update

I think occasionally about heredity as an AD risk factor, observing myself and wondering about whether I will follow my mother’s footsteps. Recently I started to do some learning about gene therapy generally, and so did some quick exploration on whether and where gene therapy is being applied to AD.

A “Scoping Review” was published in the Journal of Alzheimer’s Disease — (paywall) — “Effective, disease modifying therapies for Alzheimer’s disease (AD) remain a quandary, following a panoply of expensive failures in human clinical trials (boy, I’ll say.) Here’s a longer article on CRISPR-Cas9, the technology that has revolutionized gene therapy and is being used in manipulating neuronal genes.

Here’s a couple of genetic treatments being explored

- Brain-derived neurotrophic factor (BDNF)- First in human, three year trial began in 2021

- APOE treatment — APOE4 gene is risk factor — therapy is being explored on how to stimulate expression of the APOE2 gene (associated with some level of protection against AD) “In 2019, Weill Medical College of Cornell University began a Phase 1 trial, set to end in January 2024, evaluating LX1001 (AAVrh.10hAPOE2) in 15 volunteers who carry two APOE4 alleles, confirmed amyloid deposition, and a clinical diagnosis of MCI to moderate dementia. In March 2022, the FDA granted LX1001 Fast Track designation.” Preliminary results in late 2022 were promising.

It’s worth noting that the very recent advent of CRISPR technology will speed up the development and application of gene therapies across a range of diseases. Some work on this is summarized here. We live in interesting times.

Pharma Update

Aduhelm — “CMS released its final NCD in April last year in a move that spelled the end of the road for Aduhelm. The Medicare agency said it would allow coverage for drugs designed to clear amyloid plaques from the brains of Alzheimer’s patients, but only if those patients were enrolled in approved clinical trials.

Remternetug — Promising but early results.

Leqembi/Lequenimab — Approved to sell under “accelerated review”, Eisai reports sales of the drug in the US are “ahead of expectations.” Eisai has priced Leqembi at $26,500 per year…patients currently taking Leqembi are either part of a programme to support uninsured and under-insured individuals, or are paying the full cost out of pocket. (Medicare not covering yet, see below.) A ruling on full FDA approval for Leqembi is expected in the summer of this year. A consumer watchdog has also questioned Leqembi’s cost effectiveness.

And there is still an overhang of doubt, related to the amyloid hypothesis question (see below) — a recent articleobserves “While AD clinical trials determine, statistically, if a treatment group declines more slowly than the placebo control group, they do not set out to determine the minimum difference that would be noticeable by a patient, caregiver, or physician.” Seems like that would be nice to know for a price tag of $26,500/year. Here’s a longer discussionof this issue.

AC Immune — early results on an anti-amyloid beta vaccine ACI-24.060.

Insurance Update

Medicare and the FDA are not moving in sync these days. After the controversy over Aduhelm, the US Centers for Medicare and Medicaid Services (CMS) are moving more carefully. “At this time, CMS is not reconsidering the national coverage determination (NCD) for FDA-approved monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease,” — meaning Aduhelm and Leqembi.

Amyloid Hypothesis Update

Still no news on the fraud accusations, but here’s a report from a conference exploring what happens after the initial goal of removing plaque is partially achieved.

New data from several programs deepened the field’s understanding of what happens when amyloid plaque is cleared from a person’s brain. Different sets of trial data painted a remarkably consistent picture, showing that mopping up large amounts of plaque blunts downstream biomarkers of tau pathology, inflammation, and neurodegeneration.

But are those biomarkers precisely measures of dementia? A recent report notes that dementia are declining, but plaque levels at time of death have been similar among AD and non-AD patients. Hmm.

Neuromodulation Update

Not specific to AD but a promising development on the application of neurostimulation in wearable/portable devices from Neuroelectrics: “In a pilot clinical trial, epilepsy patients experienced a 47 percent decrease in seizure activity when using the cap. This ‘sense and stimulate’ system could also be used to treat depression, and the company hopes to start a clinical trial for that application soon.” The device was granted “breakthrough” designation by the U.S. Food and Drug Administration (FDA) for treatment of epilepsy, but the Centers for Medicare and Medicaid Services (CMS) currently does not cover products with this designation. Legislation has been introduced in the current Congress to reconsider that decision.

Previous Dispatches

See the AFAIK Archive.