An Update from Duke Health October 29, 2021
After careful review and thoughtful deliberation, Duke Health has decided it will not provide aducanumab for the treatment of Alzheimer’s disease at this time.
This decision was made after evaluation by Duke’s Pharmacy Medication Management Committee, which includes providers from various specialties and medication experts, who review all medications for their availability at Duke Health.
We understand that some patients may be disappointed, but based on current data including information on safety and clinical benefit, we believe this is the best decision for our patients. If new research or data become available, we may reconsider our decision in the future.
We are committed to caring for patients with Alzheimer’s, their families, and caregivers. Duke recently announced a collaboration with the University of North Carolina at Chapel Hill to establish an Alzheimer’s Disease Research Center (ADRC), part of a federally funded national network of similar centers. We hope that this research will benefit patients, as well as their loved ones, that are affected by Alzheimer’s disease.
How did this happen? The rationale for testing a drug that enhances clearance of amyloid-β comes from the identification of rare mutations that enhance deposition of amyloid-β in the brain that is associated with early-onset AD; the finding that enhanced clearance of amyloid-β in mouse models with these gene defects improves behavioral outcomes; and evidence that people with sporadic or genetic AD have abnormal deposition of amyloid-β in the brain many years prior to dementia. The assumption is that sporadic AD has pathogenic mechanisms sufficiently similar to those of genetic AD, and that enhanced clearance of amyloid-β will reduce brain damage and improve clinical outcomes. Such a rationale can form the basis for testable hypotheses and the design of clinical trials.
The studies have shown there is no meaningful signal for clinical benefit with aducanumab. Instead, the signal is for amyloid removal. Yet the studies for aducanumab and for prior synthetic amyloid removing antibodies have demonstrated no significant clinical benefit with a sizeable group of recipients developing mild to severe ARIA leading to accelerated functional decline.
So the justification really should read that bypassing this opportunity might miss minimal improvement for a small proportion of patients at the cost of significant complications for a different group, although data are lacking to even prove that minimal improvement.
Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula (I) wherein the R group is independently selected from the group consisting of H, CH3, and COCH3.
Cannabis is one of the first plants to have been used as a medicine, for religious ceremonies and recreationally, the first accounts of its use for these purposes stretching back 5000 years (reviewed in Mechoulam, 1986). However, the findings that cannabis is the unique source of a set of at least 66 compounds now known as cannabinoids (Table 1 and ElSohly, 2002) and that the psychotropic effects of cannabis are produced mainly by (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC; Figure 1) are much more recent.
In the case of No. 6,630,507, the researchers discovered that non-psychoactive compounds in cannabis may have antioxidant properties that could be beneficial in the treatment of certain neurological diseases, she said.
“This patent describes the therapeutic potential for cannabinoid chemical compounds that are structurally similar to THC, but without its psychoactive properties, thereby treating specific conditions without the adverse side effects associated with smoked marijuana,” Myles said in an e-mail.
The patent doesn’t prove the chemical compound is effective in the stated treatment, Rohrbaugh said. The compound would have to be purified, synthesized in a lab setting, subjected to extensive testing in animals and humans, and ultimately require U.S. Food and Drug Administration approval to show that it’s safe and effective for the intended purpose.
A May 2019 molecular biology study assayed eleven cannabinoids in a pre-clinical Alzheimer’s disease platform for their ability to remove intra-neuronal amyloid and neuroprotection. Nine of the 11 were able to remove intra-neuronal Ab, reduce oxidative damage and protect neuronal function (4). The combination of 2 cannabinoids- THC and CBN- led to synergistic neuroprotection.