December 14, 2010
Lenalidomide To Restore Aging Immune Systems?

Lenalidomide, a derivative of thalidomide, was developed to treat multiple myeloma. But in low doses lenalidomide appears to reverse many immune systems which occur in some (though not all) people as they age.

UCSF researchers have identified an existing medication that restores key elements of the immune system that, when out of balance, lead to a steady decline in immunity and health as people age.

The team found that extremely low doses of the drug lenalidomide can stimulate the body’s immune-cell protein factories, which decrease production during aging, and rebalance the levels of several key cytokines – immune proteins that either attack viruses and bacteria or cause inflammation that leads to an overall decline in health.

Blood tests could tell you in your 50s if your immune system is aging in a way that lenalidomide might help.

In 2009, Goetzl had studied a group of 50 elderly adults through the National Institute on Aging, examining their levels of key cytokines – Interleukin (IL)-2, IFN-gamma and IL-17 – and discovered that truly healthy 70-80 year old women had the same levels of those as did healthy 20 year olds.

However, some elderly men and frail women who showed increased levels of inflammatory diseases and weakened defenses against infections tended to have lower levels of the first two cytokines, which are protective, and higher levels of inflammatory cytokines. That imbalance, the researchers found, began in late middle age.

Lenalidomide has plenty of potential side effects. So do not take it lightly. But since this purpose for its use involves lower doses perhaps the odds of side effects are lower than for other purposes?

In this study, the team tested the drug in healthy seniors, each of whom were matched in race, gender and national origin to a healthy young adult participant. They found that extremely low levels of lenalidomide – 0.1 μM – optimally stimulated IL-2 production in the young people (21-40 years) roughly sevenfold, but stimulated IL-2 production in patients over age 65 by 120-fold, restoring them to youthful levels for up to five days. At that dosage, the drug also increased IFN-gamma up to six fold in the elderly patients, without suppressing IL-17 generation.

The UCSF researchers are going to continue to explore its use for aging immune systems. They are also exploring other drugs for this purpose.

Share |      Randall Parker, 2010 December 14 12:04 AM  Aging Drugs


Comments
Lou Pagnucco said at December 14, 2010 10:19 AM:

Good news.

Thalidomide-derivatives inhibit TNF-alpha and NF-kappab expression, and may reduce inflammatory disorders.

Both of the following discuss their use in CNS diseases-

"Thalidomide-based TNF-alpha inhibitors for neurodegenerative diseases"
http://www.ncbi.nlm.nih.gov/pubmed/15190675

"TNF-alpha inhibition as a treatment strategy for neurodegenerative disorders: new drug candidates and targets"
http://www.ncbi.nlm.nih.gov/pubmed/17908040

Also since thalidomide (and, hopefully this derivative) is anti-angiogenic, it may be useful against cancer and other conditions related to invasive angiogenesis.


Randall Parker said at December 14, 2010 8:47 PM:

Lou,

Agreed on the good news. Pretty cool result.

The problem with anti-angiogenesis compounds is that we have need for angiogenesis. In order to lower all cause mortality a drug that improves immune function needs to work for many years without major side effects.

So my hope is that either lenalidomide's anti-angiogenesis effects are weak or the dose used here would be too low to exert much effect on blood vessel growth.

Another point: Just rejuvenating the immune system ought to lower the incidence of cancer.

What I wonder: Could we get these indicators of immune system aging tested (and even by directly paying a test lab like a reader does) and then try various dietary and drug interventions to see if we could accomplish the same rejuv?

I also wonder what we'd find if we got our immune systems tested. How are our Interleukin (IL)-2, IFN-gamma and IL-17 doing? I'm curious to know.

Lou Pagnucco said at December 15, 2010 9:16 AM:

Randall,

There are so many dimensions to the human body state-variable, that unless there are large deviations, my best guess is that test results will not be too valuable. I only test for C-reactive protein. Still, since the innate immune system becomes more activated as we age, I wager that dietary and life-style choices that (usually) reduce systemic inflammation (e.g., low-calorie diet, olive oil, curcumin, green tea, exercise...) are beneficial.

RICHARD R. CRAWFORD SR. said at January 17, 2011 12:48 PM:

Sounds good
I am 70 and would like to know were I can get Lenalidomide

Patty Wisniewski said at February 8, 2011 4:13 AM:

My nephew is 3 years old & is currently in remission from Acute Myelogenous Leukemia. He was diagnosed at just 10 months old & underwent a series of chemo treatments that dramatically depleted his immune system.

Now, some 18-20 months after remission, he is still immunodepressed & they have begun immunotherapy.

I'm wondering if Lenolidamide might help restore/boost/improve his immune system.

Any info/thoughts you have on this topic would be greatly appreciated.

Sincerely,
Patty Wisniewski
patty.clemson@gmail.com

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