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Old 02-07-2015, 11:08 AM   #1
Lani
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Thumbs up Herceptin (lovingly referred to here as "Vitamin H") may become a widespread tool for

drug-delivery, increasing drug duration of action as body takes much longer to degrade hormones and other medications "fused" to herceptin. May even lead to alonger acting form of insulin!!



PUBLIC RELEASE: 6-FEB-2015
Cow immune system inspires potential new therapies
SCRIPPS RESEARCH INSTITUTE


LA JOLLA, CA - February 6, 2015 - To help people with hormone deficiencies, scientists at The Scripps Research Institute (TSRI) have developed a potential new therapy based on an unlikely model: immune molecules from cows.

Their research, published recently in the journal Proceedings of the National Academy of Sciences, shows that human hormones and antibodies can be fused together--mimicking long, stalk-like cow antibodies.

The new study, whose senior authors were Peter Schultz, the Scripps Family Chair Professor at TSRI, and Feng Wang, a principal investigator at the California Institute for Biomedical Research (Calibr), could also provide the foundation for treatments for a range of other diseases.

"We were inspired by this unique structure found in nature, and we assembled an antibody that might one day benefit humans," said TSRI Research Associate Tao Liu, co-first author of the new study with Yong Zhang at Calibr.

Many people need injections of human growth hormone (hGH) to combat conditions such as Turner syndrome (which causes short stature in females), low birth weight and other hormone deficiencies. Unfortunately, the body degrades hGH quickly, sometimes within 30 minutes.

"This means people need to inject themselves every day," explained Liu. "For a kid, that's really painful--and for a drug, that's really bad."

Antibodies, however, can last for weeks in the body. In the new study, the researchers drew inspiration from a bovine antibody study published by TSRI scientists in 2013. The bovine antibody has an unusual structure--a round base with a long amino-acid "stalk" pointing out. On the top of the stalk is a "knob region" that presumably binds to pathogens.

The researchers wondered whether they could switch the knob region with DNA from a human hormone, such as hGH. To test this theory, they used recombinant DNA technology to fuse hGH to a coiled version of the bovine antibody's stalks.

This fusion was stable and maintained the function of hGH, so they next tried making an antibody-hormone molecule without any cow DNA, so that the molecules might someday be applied in human therapy. They used the humanized anti-cancer antibody Herceptin® as the antibody base in the new treatment.

The researchers then tested their antibody-hGH molecule in rat models. They found that hGH-deficient rats that received the treatment grew normally. In fact, the treated rats only needed injections two times a week to grow, compared with daily injections for rats given hGH without the antibody base.

"It acts just like the normal growth hormone," said Liu. "This means the treatment might only need to be injected once a week or even once a month in humans. It would be so much easier for patients."

To further test their method, the researchers attached Herceptin® to leptin, a hormone that regulates body weight. They showed that the antibody-leptin molecule was just as effective in mice as natural leptin--and it didn't have to be injected as often. Subsequent experiments showed no harmful side effects from the treatments.

The research team is working to optimize the treatment for potential use in humans, and Liu hopes the method could someday deliver longer-lasting doses of hGH--or maybe even insulin to treat type 2 diabetes--to patients in need.

###

In addition to Liu, Zhang, Schultz and Wang, authors of the study "Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists," were Mingchao Kang and Xiaozhou Luo of TSRI; and Yan Liu, Ying Wang, Haiqun Jia, Dawna Caballero, Jose Gonzalez, Lance Sherwood, Vanessa Nunez, Danling Wang and Ashley Woods of Calibr. For more information, see http://www.pnas.org/content/112/5/1356.

This research was supported by Calibr.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Last edited by Posts; 02-11-2015 at 07:23 PM..
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Old 02-07-2015, 01:08 PM   #2
StephN
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Wink Re: Herceptin (lovingly referred to here as "Vitamin H") may become a widespread tool

Thanks, and please keep an eye out for any such use in humans!

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"When I hear music, I fear no danger. I am invulnerable. I see no foe. I am related to the earliest times, and to the latest." H.D. Thoreau
Live in the moment.

MY STORY SO FAR ~~~~
Found suspicious lump 9/2000
Lumpectomy, then node dissection and port placement
Stage IIB, 8 pos nodes of 18, Grade 3, ER & PR -
Adriamycin 12 weekly, taxotere 4 rounds
36 rads - very little burning
3 mos after rads liver full of tumors, Stage IV Jan 2002, one spot on sternum
Weekly Taxol, Navelbine, Herceptin for 27 rounds to NED!
2003 & 2004 no active disease - 3 weekly Herceptin + Zometa
Jan 2005 two mets to brain - Gamma Knife on Jan 18
All clear until treated cerebellum spot showing activity on Jan 2006 brain MRI & brain PET
Brain surgery on Feb 9, 2006 - no cancer, 100% radiation necrosis - tumor was still dying
Continue as NED while on Herceptin & quarterly Zometa
Fall-2006 - off Zometa - watching one small brain spot (scar?)
2007 - spot/scar in brain stable - finished anticoagulation therapy for clot along my port-a-catheter - 3 angioplasties to unblock vena cava
2008 - Brain and body still NED! Port removed and scans in Dec.
Dec 2008 - stop Herceptin - Vaccine Trial at U of W begun in Oct. of 2011
STILL NED everywhere in Feb 2014 - on wing & prayer
7/14 - Started twice yearly Zometa for my bones
Jan. 2015 checkup still shows NED
2015 Neuropathy in feet - otherwise all OK - still NED.
Same news for 2016 and all of 2017.
Nov of 2017 - had small skin cancer removed from my face. Will have Zometa end of Jan. 2018.

Last edited by Posts; 02-11-2015 at 07:37 PM..
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Old 02-07-2015, 06:20 PM   #3
Lani
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Re: Herceptin (lovingly referred to here as "Vitamin H") may become a widespread tool

thanks--Just what I needed to know!

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Old 02-11-2015, 11:04 AM   #4
RobinP
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Re: Herceptin (lovingly referred to here as "Vitamin H") may become a widespread tool

Sounds like Herceptin's use here is gone weird, a bit off course for its orginal use, Lani.
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Old 02-12-2015, 01:02 PM   #5
Lani
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Thumbs up Re: Herceptin (lovingly referred to here as "Vitamin H") may become a widespread tool

There are many drugs whose use has gone off-purpose allowing it to help many more people than it helped in its original indication. Many have benefited as it is much quicker to get an already approved drug utilized for another purpose--first, off-label, then with approval.

Here it is not the drug itself doing the work, but rather its attachment as a combination with something else. (like with tdm1) here rather than serving as a trojan horse and guidance system as with TDM1, serving as a body guard to allow the other drug/hormone to avoid things that break it down so it last long enough to be useful.
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