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Drug seems to reverse age-related cognitive decline in mice

By Brian Buntz | December 2, 2020

ISRIB

[Image of the ISRIB molecule courtesy of Wikipedia]

An experimental drug appeared to restore normal memory and cognition function in mice, according to researchers at the University of California, San Francisco (UCSF).

Known as ISRIB, the drug is an integrated stress response inhibitor. Earlier laboratories suggested the drug holds promise in treating disorders ranging from traumatic brain injury to noise-related hearing loss to prostate cancer.

The scientists noted in the study published in eLife that normal aging activates the integrated stress response, contributing to changes in brain function and memory. In particular, aging leads to diminished protein synthesis within the brain related to protein folding defects. While ISR plays a role in curbing abnormal cellular function in the short-term, it can contribute to age-related disorders when permanently activated.

The study showed that ISRIB reversed ISR activation in the brain, stemming spatial memory deficits and boosting working memory in aging mice. ISRIB also spurred the rejuvenation of brain and immune cells.

The effects of the drug were rapid, occurring after a few doses. “ISRIB’s extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological “blockage” rather than more permanent degradation,” explained Susanna Rosi, a UCSF professor in prepared remarks.

The researchers tested mice’s cognitive abilities by watching them escape from a modified Barnes maze and monitoring their neuronal activity. Older mice that received small doses of ISRIB in the course of a three-day training period performed as well as younger mice and had improved function in the hippocampus. Their cognitive ability persisted three weeks after treatment.

In 2013, UCSF researchers announced the ISRIB molecule improved memory performance in normal mice.

Peter Walter, another professor at UCSF, led a team that discovered ISRIB in 2013. The molecule has since been patented and licensed to the Google-related company Calico.

A 2016 STAT profile on Walter noted that some scientists were skeptical of the molecule, citing its potential to interfere with typical cellular performance. ISRIB could be years or even decades away from human testing, according to those researchers.

The researchers plan on investigating ISRIB’s potential in treating other disorders such as Alzheimer’s disease and diabetes.


Filed Under: Drug Discovery, Neurological Disease
Tagged With: age-related cognitive decline, ISRIB, UCSF
 

About The Author

Brian Buntz

As the pharma and biotech editor at WTWH Media, Brian has almost two decades of experience in B2B media, with a focus on healthcare and technology. While he has long maintained a keen interest in AI, more recently Brian has made making data analysis a central focus, and is exploring tools ranging from NLP and clustering to predictive analytics.

Throughout his 18-year tenure, Brian has covered an array of life science topics, including clinical trials, medical devices, and drug discovery and development. Prior to WTWH, he held the title of content director at Informa, where he focused on topics such as connected devices, cybersecurity, AI and Industry 4.0. A dedicated decade at UBM saw Brian providing in-depth coverage of the medical device sector. Engage with Brian on LinkedIn or drop him an email at bbuntz@wtwhmedia.com.

Comments

  1. Bernard Callens says

    December 9, 2020 at 11:55 am

    When can we test ISRIB on humans having Parkinson disease?

    • Zachari I Partridge says

      December 28, 2020 at 12:23 pm

      I’m interested in knowing when isrib can be tested in humans with Parkinson’s as well.

  2. Dulce Camamile says

    December 28, 2020 at 3:27 pm

    This is great news! I’m an 84-year old whose memory was pretty good for my age until recently. However, in the last two years, my memory began to act up almost — exclusively in the names category. I remember events, dates, etc. but when it comes to remembering the names of everyday things, then I’m in trouble. 80% of the time, I need to stop while formulating a sentence and search my memory, hard, just to remember, for instance, that the name of that thing under my head at night time is — oh yes, “pillow.” Most times though, the name will just not come to mind, and I need to Google it. Consequently, I would like to volunteer for the human trials, where could I do it?

  3. Hank Boudreaux says

    December 31, 2020 at 5:15 pm

    When will clinical tests on humans with Dementia begin ?

  4. Candy O'Sullivan-Sutherland says

    January 1, 2021 at 11:00 am

    I was diagnosed with Cognitive Brain Damage, Parkinsonism, Dystonia, Akathisia,… from Zoloft a dangerous SSRI Antidepressant prescribed over 25 years… I stopped all prescribed psych meds including Ativan 6mg/day, Ambien at night,… but my brain is still fried. Could ISRIB help me work again? It has been 5 years, the Dell Technologies DellEMC health benefits I paid into over 20 years, did not/does not cover cognitive brain damage, neuromuscular conditions,… with doctor notes. I need to be able to support myself again instead of depending on SSDI.

  5. Nancy McPartlin-Gardella says

    January 1, 2021 at 3:15 pm

    I wonder if this drug would be beneficial for individuals living with autism? Please move the research forward. Good luck and I am keeping my fingers crossed.

  6. Jeff Miller says

    January 3, 2021 at 5:49 pm

    I would be a willing participant in any sort of study regardless of the parameters of the study when they begin.

  7. Marilyn Watts says

    January 3, 2021 at 11:42 pm

    Oh please is there some way you could think of working with humans! My friend of over 45 years, a brilliant radiation oncologist had a terrible fall down stairs, and now we have had to place her in a memory care facility…day by day she regains some cognition….now she herself wants to know if there are any graduate students etc… willing to work with her. This is a tragedy with a brilliant human brain. How do we go about finding help?
    Please help

  8. Michael Kent says

    January 5, 2021 at 9:30 pm

    Please start human trials as soon as possible! I will volunteer. This is legit research at a well respected university with well respected researchers.

  9. Sally Um says

    January 12, 2021 at 8:53 pm

    My son, who was diagnosed with autism at 3 years, is now 18. His cognitive abilities are below average for his age. Is he eligible to participate in this trial?

    • Brian Buntz says

      January 12, 2021 at 9:09 pm

      Hi Sally,

      From what I have seen, there are no planned human trials related to this investigational drug yet.

  10. rosalie lee says

    January 26, 2021 at 1:15 pm

    Could you please tell me if this drug ISRIB has been tested on humans yet as I HAVE two grandsons with autism and am desperate to get help for them.

    • Brian Buntz says

      January 27, 2021 at 11:23 pm

      Hi Rosalie, unfortunately, I am not aware of any human studies involving ISRIB, but I saw in a separate article that the researchers are motivated
      to “push it to humans as soon as possible.”

  11. Karen Arrington says

    January 26, 2021 at 11:58 pm

    This seems like an amazing study.
    You need to do everything possible to make human study’s possible.
    It is painful to watch loved ones suffer with dementia.

  12. Gaetano Stomboli says

    January 31, 2021 at 7:53 pm

    My daughter is 20 years old and she has mental problems. Can this Drug help her? When will ISRIB be available for humans? Thank you.

    • Brian Buntz says

      February 2, 2021 at 10:46 pm

      Hi Gaetano,

      Human trials have not yet begun for the drug, so it is hard to speculate at this point when it might be available.

  13. Pam says

    February 3, 2021 at 10:12 pm

    This research sounds incredible. However there must be a reason why it has not been tested on humans.
    There must be be a glut of volunteers, just waiting to be asked

  14. JT says

    February 4, 2021 at 6:29 am

    Forget Covid , and Fast Track the trials and get this to the millions who are suffering and dying and help the pain from their caretakers and love ones.

  15. Carmela Holt says

    February 7, 2021 at 3:00 am

    I find this fascinating and would volunteer my husband who has frontotemporal lobe dementia. Diagnosed at 66.…he is now 70.
    Too young…please..please let all know when human trials become reality.

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