MIT : Un nuovo modello computazionale per lo sviluppo di farmaci basati su anticorpi

[D.O.S.]

MIT model could improve some drugs’ effectiveness

MIT researchers have developed a computer modeling approach that could improve a class of drugs based on antibodies, molecules key to the immune system. The model can predict structural changes in an antibody that will improve its effectiveness. The team has already used the model to create a new version of cetuximab, a drug commonly used to treat colorectal cancer, that binds to its target with 10 times greater affinity than the original molecule. The work, which appeared Sept. 23 in an advance publication of Nature Biotechnology, results from a collaboration using both laboratory experiments and computer simulations between MIT Professors Dane Wittrup and Bruce Tidor. “New and better methods for improving antibody evelopment represent critical technologies for medicine and biotechnology,” said Wittrup, who holds appointments in MIT’s Department of Biological Engineering and Department of Chemical Engineering. Tidor holds appointments in biological engineering and the Department of Electrical Engineering and Computer Science. Antibodies, which are part of nature’s own defense system against pathogens, are often used for diagnostics and therapeutics. Starting with a specific antibody, the MIT model looks at many possible amino-acid substitutions that could occur in the antibody. It then calculates which substitutions would result in a structure that would form a stronger interaction with the target. “Combining information about protein (antibody) structure with calculations that address the underlying atomic interactions allows us to make rational choices about which changes should be made to a protein to improve its function,” said Shaun Lippow, lead author of the Nature Biotechnology paper. “Protein modeling can reduce the cost of developing antibody-based drugs,” Lippow added, “as well as enable the design of additional protein-based products such as enzymes for the conversion of biomass to fuel.” Lippow conducted the research as part of his thesis work in chemical engineering at MIT and is now a member of the protein engineering group at Codon Devices in Cambridge. “Making drugs out of huge, complicated molecules like antibodies is incredibly hard,” said Janna Wehrle, who oversees computational biology grants at the National Institute of General Medical Sciences, which partially supported the research. “Dr. Tidor’s new computational method can predict which changes in an antibody will make it work better, allowing chemists to focus their efforts on the most promising candidates. This is a perfect example of how modern computing can be harnessed to speed up the development of new drugs.” Traditionally, researchers have developed antibodybased drugs using an evolutionary approach. They remove antibodies from mice and further evolve them in the laboratory, screening for improved efficacy. This can lead to improved binding affinities but the process is time-consuming, and it restricts the control that researchers have over the design of antibodies. In contrast, the MIT computational approach can quickly calculate a huge number of possible antibody variants and conformations and predict the molecules’ binding affinity for their targets based on the interactions that occur between atoms. Using the new approach, researchers can predict the effectiveness of mutations that might never arise by natural evolution. “The work demonstrates that by building on the physics underlying biological molecules, you can engineer improvements in a very precise way,” said Tidor. The team also used the model with an antilysozyme antibody called D44.1, and they were able to achieve a 140-fold improvement in its binding affinity. The authors expect the model will be useful with other antibodies as well. The research was funded by the National Science Foundation and the National Institutes of Health. Wittrup and Tidor also co-teach a class focusing on connecting fundamental molecular and cellular events to biological function through the use of mathematical models and computer simulations.

preso da http://web.mit.edu/newsoffice/2007/techtalk52-3.pdf a pagina 4

[HYPERR]

Molto interessante dato che bisogna considerare che i famaci biologici sono sempre più utilizzati ed hanno dimostrato un'alta efficacia.
In questi giorni sono in reumatologia e proprio oggi il prof ha speso un po' di tempo per chiarire alcuni aspetti riguardanti i farmaci biologici ed in particolare quelli rivolti verso l'artrite reumatoide.

[drakend]

Originariamente inviato da HYPERR

Molto interessante dato che bisogna considerare che i famaci biologici sono sempre più utilizzati ed hanno dimostrato un'alta efficacia.
In questi giorni sono in reumatologia e proprio oggi il prof ha speso un po' di tempo per chiarire alcuni aspetti riguardanti i farmaci biologici ed in particolare quelli rivolti verso l'artrite reumatoide.

Per farmaci biologici si intendono i virus ogm ( ) che fanno fuori i batteri delle malattie?

[HYPERR]

I farmaci biologici o mab (Monoclonal anti body), cioè anticorpo monoclonale, sono sostanze che, come gli anticorpi prodotti dal sistema immunitario, si legano a certe specifiche sostanze. Nel caso di questi farmaci antireumatici, l'anticorpo si lega ai mediatori dell'infiammazione e, per intendersi, spegne l'interruttore della reazione infiammatoria in un punto più a monte rispetto ai farmaci usati finora.
Più in generale si può dire che i farmaci biologici sono costituiti da anticorpi o falsi bersagli che "ingannano" le citochine della cascata infiammatoria in modo da limitarla.
Il termine biologico indica il fatto che sono proteine prodotte in organismi viventi e possono essere "disegnate" al fine di bloccare specifici step molecolari. In pratica i farmaci biologici sono un gruppo di proteine prodotte mediante l’ingegneria genetica (tecnologia del DNA ricombinante) o sintetizzate da cellule umane intere o estratte dal sangue; essi sono prodotti negli organismi viventi e possono essere impiegati per modificare specificatamente le reazioni immuni.

[D.O.S.]

Originariamente inviato da HYPERR

.......
essi sono prodotti negli organismi viventi e possono essere impiegati per modificare specificatamente le reazioni immuni.

vengono usati pure per combattere il cancro.
il Rituxan viene usato con ottimi risultati pure nei linfomi e da pochissimi effetti collaterali.
solo che costa un casino di soldi e lo prescrivono con il contagocce .....

[HYPERR]

Per quanto riguarda il trattamento dei tumori non sono molto informato. Però so per certo che in reumatologia sono abbastanza usati ovviamente sotto controllo diretto e dopo opportuni esami dato che in ogni caso si verifica un'immunosoppressione (quindi si fanno test per HIV, Tubercolosi, epatite c...).