Question: Hi, Dr. Benzi. I have Parkinson’s disease and am searching for things that can help improve my quality of life. Attached below is an article about ISRIB and Calico, who is researching this molecule. When I searched their web site, I was not able to locate any info on this and whether they are doing studies on humans. Can you tell me where I might find more info, and whether it’s worth looking into further? Best regards, J

Article: Drug reverses age-related cognitive decline within days | Lab: Calico Labs

Reply: Hello J, and thanks for writing. As our first “Ask Dr. Benzi” writer, we will send you a non-bullshit book of your choice. I’d promise to send you an autographed copy of my book, and maybe I will, but I don’t want you to wait that long for your reward.

ISRIB stands for integrated stress response inhibitor, a pretty catchy name for a molecule, and one that was given to it by the Calico lab. It is a compound that reverses the effects of the eukaryotic translation initiation factor 2a (EIF2A), a protein that in turn is involved in the formation of puromycin-sensitive 80S preinitiaion complexes (duh). 

To be honest with you, I knew nothing about ISRIB before writing this blog and learned about what all of these things stood for through Wikipedia. I got other information from PUBMED, clinicaltrials.gov (more below) and the Calicolabs website.

To answer your first question, which is a great first question: there are currently NO studies demonstrating any benefit of ISRIB in people and there are currently NO active trials of this compound in people. Medicalxpress, like a lot of news outlets, puts up very provocative headlines to generate hype and attract advertisers. “Drug Reverses Cognitive Aging Within Days” sounds exciting, perhaps even revolutionary. But the fact of the matter is that this headline was related to a study (here) in showing ISRIB improved spatial memory performance in older mice. 

While this is a cool finding, we honestly have no idea whether or not it will work in people. This is an important point because there have been literally thousands of compounds generating thousands of exciting headlines about reversing aging, curing cancer, stopping Alzheimers… that were based on animal studies, NONE of which has proven itself to be safe or effective in people. If ISRIB actually was proven to reverse age-related cognitive decline in people (even if it took weeks and not days), you wouldn’t just be reading about it in Medicalxpress.

Some takeaway tips so that you can answer questions like these yourself in the future:

  1. Wikipedia is a reliable source for basic information such as scientific terms.
  2. PUBMED (blog on this coming soon) is the go-to website for most doctors and scientists looking to track down the latest research. In this case I searched “ISRIB”, limited my search to clinical trials in humans and came up with zero studies.
  3. Clinicaltrials.gov (blog on this soon) is a great website to find out what studies are happening in people and which may be looking for volunteers. There were no studies listed with ISRIB at the time of this blog.
  4. Be wary of exciting medical headlines in the news. Most of the time they are over-hyped spin on a much less exciting study. I checked Medicalxpress to see what else they were covering and found “Wearable sensor may signal you’re developing COVID-19—even if your symptoms are subtle.” This headline was based on a study of 50 people testing a device that simply monitored people’s temperatures. Not surprisingly, people with higher temperatures were more likely to have COVID.
  5. Be wary of getting news directly from the websites of laboratories or researchers, particularly, as is the case for Calicolabs, they are interested in attracting investors, attracting graduate students, developing products… I am not saying that these labs are not doing good, and often even great, science. I am saying that these websites should be viewed more like a marketing infomercial than a source for scientific facts. If you want the real story, I would again turn to pubmed.