Naked Mole Rats and Fighting Degenerative Disease

This post was authored by @MikeMadarasz of the Institute for International Research

Did you know that the naked mole rat holds the record for the longest living rodent?  It’s a nice piece of trivia, yes, but the longevity of this animal may actually provide us clues about fighting degenerative diseases such as Alzheimers and Parkinsons.  Naked mole rats have been known to live for as long as 31 years—an incredible age based on their size.  In comparison, mice live four years at the most.  This is something that has piqued the interest of scientists for years.

A recent study from the University of Texas Health Science Center in San Antonio has made connections between the extended lifespan of these rodents and the chaperone protein HSP25.  HSP25, as well as other chaperone proteins, serve as a sort of protein audit team by quickly eliminating those that are incorrectly produced or defective.  These flawed proteins are capable of aggregating and forming “clumps”, which have been associated with degenerative diseases.  

Recently, researchers have been able to definitively correlate the presence of HSP25 in tissue with longevity.  Says Karl Rodriguez, Ph.D., a postdoctoral fellow at the University of Texas Health Science, "If we can understand how HSP25 levels are regulated, what it’s function is and how it contributes to cell health, we might find ways to use this protein to combat devastating age-related diseases."  Rodriguez cites animals with higher levels HSP25 as being more “primed to react” to faulty proteins and in turn, maintain cell health.  Finding ways to increase the human equivalent of the HSP25 protein (HSP27) could potentially help prevent these diseases.

Said Rochelle Buffenstein, Ph.D, the study’s senior investigator, "There's still a lot we can learn from extremely long-lived animals. Use of such models enables us to evaluate whether nature—through millions of years of evolutionary experimentation—has already evolved the best way to maintain cellular integrity and thereby delay and attenuate the aging process. HSP25 may be one such evolved protein."

Read the full press release here.

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ADCs: Where is There Room for Improvement?

There’s been an explosion of interest in antibody drug conjugates (ADCs) over the last few years.  Those in the field now find themselves asking “Why shouldn’t we work with ADCs?” rather than “Why should we?”.   Bob Lutz, VP of Translational Research and Development at ImmunoGen, says this is a big departure from only a short time ago.  We recently caught up with Bob to pick his brain on some of the other developments in the field.  Check out what he had to say.  

What do you think will be the most important factors leading to increased success in the ADC field?

Interesting question. I think the biggest game changer wouldn’t point at any particular technology at this point. I think the biggest game changer will be that instead of about 50 scientists working on the problems in the field say, 10-15 years ago, maybe there are as many as 5,000 working now. I think that increased brain power is the most important factor that will lead to future successes. So many more things will be tried. We’ll learn so much more from each other as we watch what succeeds and what fails and that is very exciting.

To me, I think if I had to pick technologies, where I’m most hopeful they’ll make a difference is change from antibodies only as the delivery vehicle. I think the new scaffolds do provide an area of design flexibility that will make a big difference. I don’t know which ones will be the right ones. I don’t know which properties will be the right properties. But, what we’re going to get over the next half a decade is real insights to which ones do seem to provide an important event.

Then I think the other big factor for me that I would pick on the technology side, we’ve been doing a lot of work on upfront design of the ADC and what we haven’t done is spent much time on what happens to it once it starts to be degraded, once it starts to metabolize in the body. I actually think that will be when we start really focusing on design elements that deal with where it goes, what happens to it after. Very similar to, in our own lives, our consumer society going into waste management. Recycling and all that was an understanding – we had to pay attention to what happens after we’ve used something the way we’ve wanted. I think for ADCs that will be the same thing. We need to deal with ADC design options that impact what happens to the compound after it is removed from circulation. I think that will be the next important advance. I think there is only a little bit of work going on in that area at the moment.

DOWNLOAD BOB’S FULL PODCAST HERE

Bob will be keynoting at the Bioconjugates: From Targets to Therapeutics conference June 4-6 in San Francisco. You can catch him as well as the rest of our lineup of industry thought leaders.  Register here and save 20% as a reader of our blog.  Use discount code D14199BLOG.

BEST VALUE. Get three conferences for the price of one. Check out our all access passes to Protein Aggregation, Solubility and Stability and the Next Generation Protein Summit.  

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Anti-HIV Molecules: The Key Role of One Everyday Material

This post was authored by @MikeMadarasz of the Institute for International Research

“Injection molding high temperature resistant plastics provide part makers with design flexibility, high production rates, lower labor costs, and less or no finishing of molded parts.” 

Believe it or not, some of the manufacturing advantages of polymers (above) could be crucial to a key biologic development.  Polymers, a synthetic material in everything from styrofoam to credit cards, may actually be part of a solution to one day block HIV infection.  Thanks to new techniques in synthetic chemistry, scientists are now exploring ways to use polymers in biological settings. 

Dan Mitchell, a researcher at the University of Warwick, UK, is one of these scientists.  “Over the last ten or fifteen years, the types of chemical reactions used to synthesize polymers have elaborated, so you can now develop polymers of a highly defined length and size” explained Mitchell in a recent BioRadiations article.  Mitchell and his colleagues are specifically focused on the DC-SIGN protein, which play a critical role in the onset of an HIV infection, and how polymers might interact with it.  In the initial stages of HIV, the virus uses DC-SIGN receptors as a vehicle to travel to the lymph nodes.

Manipulating polymers in a way that would allow them to bind to DC-SIGN proteins could ultimately inhibit HIV infections.  In a recent paper, Mitchell and his colleagues described a high level of success in controlling these polymers.  Explains Mitchell, “Unlike mixing lots of different polymer lengths together as you would to make a composite like nylon fabric, we made polymers that were sequence-controlled at the molecular level… We had a range of molecules with different types of carbohydrate molecules at distinct points along the polymer backbone we wanted to see which ones bound to DC-SIGN better or worse, and did that correlate with the existence of sugars at specific points in those polymers?”

To answer this question, Mitchell and his team set up a series of competition assays—analyzing them with Bio-Rad’s ProteOn™ XPR36 protein interaction array system.  The results were encouraging.  Mitchell found that the polymers did indeed prevent binding on the DC-SIGN protein. 

So what’s next?  “The next step is to use these polymers in experiments with very high quality cells or even tissues,” Mitchell says. “We need to get cells from human beings, incubate them with the polymers, and study their responses. We don’t have that set up yet.”  With more research, future studies with more complex HIV models could be on the horizon. 

You can check out the full article from BioRadiations here.

We’ll have more on the latest in protein research at the Next Generation Protein Therapeutics Summit as well as IBC’s inaugural Protein Aggregation, Stability and Solubility event.

June 4-6 | San Francisco, CA

Register for Next Generation Protein Therapeutics Summit and save 20%. Use code NGP14BLOG

Register for Protein Aggregation, Stability and Solubility event and save 20%. Use code D14200BLOG

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Event Update: FDA confirms for 8th Annual Next Generation Protein Therapeutics Summit

IBC Life Sciences’ is pleased to announce Kathleen A. Clouse, Ph.D., Division of Monoclonal Antibodies Director at OBP, CDER, US FDA will deliver a keynote presentation FDA Perspective on Novel Monoclonal Antibody Development Pathways on Friday, June 28 at the 8th annual Next Generation Protein Therapeutics Summit in San Diego, CA.

This is a rare and valuable opportunity to hear first-hand from the FDA about their perspectives on the development of novel antibody-based molecules and scaffolds. Gain new ideas to help you engineer novel molecules and formats to meet regulatory expectations.

Dr. Clouse joins our faculty of over 30 international industry and academic experts in protein therapeutics design and development whose presentations will give you new ideas and practical strategies you can apply right away in your own laboratory.

For full program details, download the agenda.  As a reader of this blog, when you register to join us and mention code NGPT13JP, you'll save 20% off the standard rate.  This event is co-located with Bioconjugates: From Targets to Therapies, so you'll have access to sessions from both events!

Have any questions?  Feel free to email Jennifer Pereira.

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Podcast: A look at the Amunix drug-conjugation platform

We recently sat down with Volker Schellenberger, Ph.D., President, Amunix, Inc. who will be joining us for the Next Generation Protein Therapeutics Summit. During our conversation  we discussed the Amunix drug-conjugation platform, the therapeutic window of XTEN-based drug conjugates, controlling the chemical structure of XTEN-drug conjugates, the manufacturability of XTEN conjugates and more. Download the podcast to hear the whole conversation.

Dr. Schellenberger will be presenting XTEN: A Protein-Based Polymer that Enables Bioconjugates with Precisely Controlled Chemical Composition on Thursday, June 27 at the Next Generation Protein Therapeutics Summit. If you'd like to know more about his presentation and the rest of the program, download the agenda. If you'd like to join us in Coronado, as a reader of this blog when you register to join us and mention code PTJP13, you'll save 20% off the standard rate. If you have any questions, feel free to email Jennifer Pereira.

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