 |
|
A protein sequence associated with Huntington's disease may become life-saving vaccine component
June 11, 2008On June 10, 2008 the scientific journal "Vaccine" published a paper by the Massachusetts based biotech company Cure Lab, Inc., demonstrating that a protein sequence important in neurodegenerative Huntington's disease can be safely used as a new generation of vaccine adjuvants.
The major component of every vaccine is an antigen that elicits specific immunity to a particular virus, bacteria or even cancer cells. Search for better antigens is one of the most pressing medical and public health necessities, and the biotech industry invests heavily in this research. However, antigens are able to generate a limited immune response if administered alone. In order to be protective or therapeutic, vaccine compositions have to be supplemented with adjuvants, strong facilitators of the immune response. In the search for efficient adjuvants that are also non-toxic, scientists at Cure Lab, Inc. discovered a novel paradigm that capitalizes on insights from recent breakthroughs in understanding the fatal neurodegenerative disorder, Huntington's.
Huntington's disease results from mutations in the protein huntingtin, which contains a sequence of polyglutamine residues (polyQ). In healthy individuals, huntingtin contains less than 35 glutamines in the polyQ segment. However, in neurons of Huntington's patients, the number of glutamine residues in the sequence expands to more than 36. This induces protein self-aggregation, or formation of big protein "chunks", and eventually causes neuronal dysfunction. Recent research findings indicate that attachment of a prolonged polyQ segment to almost any protein promotes its aggregation.
"There were two ideas - said Alex Shneider, Cure Lab's founder and CEO- which stimulated us to test if attachment of a long polyQ "tail" to an antigen can enhance immune response to vaccination". First, he noticed that small aggregates formed by an antigen fused to a polyQ tail resembled the droplets that conventional adjuvants formed with antigenic peptides exposed on their surface. Dr. Shneider hypothesized that these polyQ containing aggregates were easily taken up by antigen-presenting cells, as is the case with adjuvant droplets, triggering the immune response.
Another hypothesis was proposed by Michael Sherman, professor at Boston University Medical School and scientific consultant at Cure Lab. "We knew- said Michael Sherman- that polyQ aggregates are destroyed in cells by a special degradation system, called autophagy. Interestingly, autophagy plays a key role in the processing of certain antigens, which is critical for the immune response. So, attachment of a polyQ tail should specifically target the antigen to autophagy, which in turn should facilitate the response. Thus, polyQ would serve as a molecular adjuvant".
There are two branches to the immune system. One is responsible for developing antibodies against bacteria, viruses and toxins freely circulating in the organism. Another is aimed at eliminating virus-infected or cancer cells. Cure Lab's paper demonstrates that the new polyQ-based adjuvant efficiently enhances both branches of the immune response to a poor model antigen. Importantly, the adjuvant caused no apparent toxicity in mice.
Many questions remain to be answered. The adjuvant properties of the polyQ tail will have to be tested for each individual antigen of medical and veterinary importance. However, this work may launch a new era in vaccine development, the era of molecular adjuvants.
Cure Lab, Inc.
"There were two ideas - said Alex Shneider, Cure Lab's founder and CEO- which stimulated us to test if attachment of a long polyQ "tail" to an antigen can enhance immune response to vaccination". First, he noticed that small aggregates formed by an antigen fused to a polyQ tail resembled the droplets that conventional adjuvants formed with antigenic peptides exposed on their surface. Dr. Shneider hypothesized that these polyQ containing aggregates were easily taken up by antigen-presenting cells, as is the case with adjuvant droplets, triggering the immune response.
Another hypothesis was proposed by Michael Sherman, professor at Boston University Medical School and scientific consultant at Cure Lab. "We knew- said Michael Sherman- that polyQ aggregates are destroyed in cells by a special degradation system, called autophagy. Interestingly, autophagy plays a key role in the processing of certain antigens, which is critical for the immune response. So, attachment of a polyQ tail should specifically target the antigen to autophagy, which in turn should facilitate the response. Thus, polyQ would serve as a molecular adjuvant".
There are two branches to the immune system. One is responsible for developing antibodies against bacteria, viruses and toxins freely circulating in the organism. Another is aimed at eliminating virus-infected or cancer cells. Cure Lab's paper demonstrates that the new polyQ-based adjuvant efficiently enhances both branches of the immune response to a poor model antigen. Importantly, the adjuvant caused no apparent toxicity in mice.
Many questions remain to be answered. The adjuvant properties of the polyQ tail will have to be tested for each individual antigen of medical and veterinary importance. However, this work may launch a new era in vaccine development, the era of molecular adjuvants.
Cure Lab, Inc.
More Huntington’s Disease News Articles
 | Thompson & Thompson Genetics in Medicine: With STUDENT CONSULT Online Access (GENETICS IN MEDICINE) by Robert L. Nussbaum, Roderick R. McInnes, Huntington F. Willard Through six editions, Thompson & Thompson's Genetics in Medicine has been a well-established favorite textbook on this fascinating and rapidly evolving field, integrating the classic principles of human genetics with modern molecular genetics to help you understand a wide range of genetic disorders. The 7th edition incorporates the latest advances in molecular diagnostics, the Human Genome... |
 | The Woman Who Walked into the Sea: Huntington's and the Making of a Genetic Disease by Alice Wexler A groundbreaking medical and social history of a devastating hereditary neurological disorder once demonized as “the witchcraft disease” When Phebe Hedges, a woman in East Hampton, New York, walked into the sea in 1806, she made visible the historical experience of a family affected by the dreaded disorder of movement, mind, and mood her neighbors called St.Vitus's dance. Doctors... |
 | Mapping Fate: A Memoir of Family, Risk, and Genetic Research by Alice Wexler In Mapping Fate, Alice Wexler tells the story of a family at risk for a hereditary, incurable, fatal disorder: Huntington's disease, once called Huntington's chorea. That her mother died of the disease, that her own chance of inheriting it was fifty-fifty, that her sister and father directed much of the extraordinary biomedical research to find the gene and a cure, make Wexler's story both... |
 | A New Promise by Julie Eller |
 | Faces of Huntington's by Carmen Leal-Pock Faces of Huntington's is an incredible collection of stories, essays, poems, and quotes of those who are in some way connected to Huntington's Disease. The book focuses on over sixty people who have HD, are at risk, caregivers, other family members, adn friends. It is a beacon of light in what is often a dark world. 30,000 Americans have this terminal neurological disorder. An additional... |
| Boyd's Introduction to the Study of Disease by Huntington Sheldon | |
 | Prostate Cancer Prevention and Cure by Lee Nelson The two most common cancers in men are skin cancer and prostate cancer. If you're male and over 50, statistically you have a 50% chance of getting clinically significant prostate cancer at some point in your life. Contrary to the statistics, prostate cancer is often preventable. And it's curable in most men. But awareness is key. Prostate Cancer—Prevention and Cure tells you all you need... |
 | Learning to Live With Huntington's Disease: One Family's Story by Sandy Sulaiman |
 | Sixteen and Dying (One Last Wish) by Lurlene Mcdaniel You don't know me, but I know about you.... I can't make you live longer. I can't stop you from hurting. But I can give you one wish, as someone did for me. It's hard for Anne Wingate and her father to accept the doctors' diagnosis: Anne is HIV positive. Seven years earlier, before blood screening was required, Anne received a transfusion to save her life, and the blood was tainted. Now... |
 | Devil's Dance by Richard R. Karlen "If I chance to talk a little wild, forgive me:/I had it from my father." William Shakespeare, "Henry VIII" Harry Stone's life is falling apart. At age forty-four, an English professor, he begins to dress in black and white and ride motorcycles in the night. After getting one of his students pregnant, he is forced to resign from the University. Unable to tolerate his strange,... |
| © 2008 BrightSurf.com |