In the wake of the FDA approval of Aduhelm for Alzheimer’s, what other therapies are being tested in clinical trials this year? [yeah, “wake” might just have a double meaning here].
Using clinicaltrials.gov, a searchable database, and the search terms listed, one gets this result: “73 Studies found for: therapy | Recruiting Studies | Interventional Studies | Alzheimer Disease | United States | Phase 2, 3, 4.”
In the US, there are a million or so new cases/year of Alzheimer Disease (AD) or dementia age >65, according to a 2021 report. Cancer has probably 2M new cases a year, but it’s probably unfair to compare the raw number of clinical trials for cancer (> 3,000 listed, lots of biotech/Pharma).
Diabetes might be a better comparison for the number of clinical research studies. Diabetes in the US has an incidence of about 1.4M new cases/year . Using the same search parameters, one can find 196 clinical therapy trials, at least twice the number compared to AD (the search result lists 25/73 trials for behavioral or other side issues in AD; many trials in diabetes were also for side issues).
This isn’t meant to be a review, but looking at the AD studies recruiting volunteers for their studies, one notices a broad range of therapeutic ideas being tested.
At least three trials are using mesenchymal stem cells (MSC). The brain is derived from embryonic ectoderm, not mesoderm, which gives rise to mesenchymal cells. But MSC may help rodents so treated through inflammatory or immune mechanisms, not as a neuronal repair or rescue [AdGadfly did some clinical marrow transplant in the last century; donor hematopoietic stem cells were thought to be a kind of rescue or replacement].
Along the lines of inflammation, a T-cell monoclonal (daratumumab, approved for myeloma) and an IL-1 beta monoclonal (canakinumab, approved for sickle cell disease) are two “anti-inflammatory” medications in trials.
Amyloid beta monoclonals such as donanemab, gantenerumab and lecanemab are still recruiting subjects, although the first two had not met endpoints in previous published reports. A relatively new tau monoclonal, bepranemab, is also active. [the last three letters “m-a-b” stand for “monoclonal anti-body]
Although the SNIFF trial of nasal insulin failed to meet therapeutic goals a few years ago, the investigators are trying again and adding the diabetes drug, empagliflozin. Other diabetes meds in trials include semaglutide and dapagliflozin.
Anti-viral trials include valacyclovir (approved for Herpes) and 3TC (approved for HIV). At least half a dozen new investigational drugs are being offered with proprietary names like PQ912, CY6963, E2814 and RGI126209, mainly Phase II trials.
Using “brain stimulation” instead of “therapy” in a separate search gives 17 studies. There are several external devices, trying transcranial magnetic stimulation (picture above), transcranial alternating or direct current stimulation, transcranial sonic pulses and various transcranial photobiomodulations (some helmet-like) in trials.
There is at least one surgical deep brain electrode implant study still recruiting.
So if you’re looking, there’s a lot to choose from! There may be a lack of overall strategy, but popular notions are being tested. It takes a while to mount a clinical trial, but given the FDA’s statements about using amyloid beta as a proxy for cognitive effect, there aren’t that many amyloid trials. Let’s just hope some group, whatever they are testing, finds substantial effectiveness, so that people living with dementia can have discernible, life-modifying, better outcomes.
[oh, signing someone up for an Alzheimer’s clinical trial might not be a regular Valentine’s Day activity, and sending this out on Feb 14, might be unusual…but isn’t VD perfect for awkward gifts?]