Category Archives: Transhuman News

Precision medicine seems to be the new hot topic in the research world. President Obama spoke about precision medicine in his State of the Union speech on January 20, his budget released today requests $215M for precision medicine, and NIH just announced plans for a study of a million or more volunteers to explore precision medicine. What precisely is it? The White House website has a useful definition: getting the right treatment at the right time to the right person. The President, in an event devoted to precision medicine in the East Room last Friday [January 30, see video, below], told the story of ivacaftor, a drug that effectively treats the underlying causenot the symptomsof cystic fibrosis, but works in only 4% of patients who have a specific mutation in the gene causing this disease.

Most of the conversation about precision medicine focuses on cancer. Because cancer is a disease of genetic mutations leading to unregulated cell division, defining the precise mutations in the affected tissue have already led to breakthrough treatments for both blood and solid tissue cancers. In fact, the same mutation can occur in different parts of the body, so cancer is increasingly diagnosed in terms of its genetic and molecular signature rather than the tissue of origin. Part of the proposed precision medicine plan will involve scaling up efforts at the National Cancer Institute to find these mutations and to develop drugs or biologics as treatments.

What does precision medicine mean for mental health? Our version is the Research Domain Criteria (RDoC) project, which aims to develop more precise diagnostic categories based on biological, psychological, and socio-cultural variables. It is certainly possible that we may find specific mutations in relevant brain circuits that explain some cases of schizophrenia, bipolar disorder, or autism, just as mutations in the tumor explain cancer. NIMH has supported research on inherited genetic risk for several years; a new initiative on another class of mutations, somatic mosaicism (the term for mutations that develop after fertilization), will launch this year. But more likely, precision medicine for mental disorders will not come from a single genomic glitch. Rather, like many other areas of medicine, many genes each contribute only a small amount of vulnerability as part of an overall risk profile that includes life experiences, neurodevelopment, and social and cultural factors. RDoC assumes that we will need many kinds of data to reach precision, more like triangulating to find your position on a map. These data will draw from many sources, including symptoms, genotype, physiology, cognitive assessment, family dynamics, environmental exposures, and cultural background.

I know that RDoC sounds more complex than the cancer version of precision medicine, but that is the nature of the problem. For now, we need to embrace the complexity to identify the simpler, actionable categories that can be used in the clinic. The rationale for this approach is no different from what the President talked about for cancer or cystic fibrosisgetting the right treatment at the right time to the right person.

See the original post:
Precision Medicine for Mental Disorders

10.02.2015 - (idw) Paul-Ehrlich-Institut - Bundesinstitut fr Impfstoffe und biomedizinische Arzneimittel

Therapeutic gene transfer is considered as a promising novel strategy to treat genetic disorders and cancer. So far, target cells are often isolated from patients for this purpose, and re-administered after gene transfer. In collaboration with colleagues from the Universities of Cologne and Zurich, researchers at the Paul-Ehrlich-Institut have succeeded in developing gene transfer vehicles that target the therapy relevant cell type directly in the organism. The resulting gene transfer occurs with an extremely high degree of selectivity. A report on the research results can be found in Nature Communications in its online edition of 10.02.2015. Vectors derived from adeno-associated viruses (AAV) were used as vehicles for targeted gene transfer by the research group of Professor Christian J. Buchholz, Principal Investigator at the LOEWE Centre for Cell and Gene Therapy at Frankfurt am Main and head of the Section Molecular Biotechnology and Gene Therapy of the President of the Paul-Ehrlich-Institut. AAV is a non-pathogenic parvovirus. The only gene therapy medicinal product authorised in Europe so far, is also based on AAV gene vectors and intended for the treatment of a rare metabolic disorder.

The strategy for the generation of the new precision gene vectors was developed and implemented jointly with Dr Hildegard Bning, head of the AAV Vector Development Research Group at the ZMMK (Zentrum fr Molekulare Medizin Kln, Center for Molecular Medicine Cologne) of the University of Cologne: Through exchange of two amino acids, AAV lost its ability to bind to its natural receptor and became thereby unable to penetrate its broad range of natural target cells. Novel target structures (DARPins, designed ankyrin repeat proteins) were then attached to the surface of the modified vector particles. These structures were developed at Zurich University. The structures can be selected in such a way that they mediate a selective binding of the DARPin-containing AAV vector particles to the therapy relevant cell type only. This is what enables the AAV vector to attach to and penetrate the desired target cell. The paper referenced here reports on the use of three different DARPins, which equipped AAV vectors either with a specificity for Her2/neu, a tumour marker in breast cancer, for EpCAM, an epithelial surface protein, or for a marker of particular blood cells (CD4 on the surface of lymphocytes with distinct immunological functions).

The desired goal of a cell type specific in vivo gene transfer was also achieved with the blood cell targeted vector: AAV transferred the gene only into lymphocytes present in spleen carrying the CD4 protein target structure.

The method developed by us jointly is a very promising tool both in fundamental research and for the targeted gene transfer in medicine, explained Dr Buchholz with regard to the current research results.

Original Publication

Mnch RC, Muth A, Muik A, Friedel T, Schmatz J, Dreier B, Trkola A, Plckthun A, Bning H, Buchholz CJ (2015): Off-target-free gene delivery by affinity-purified receptor-targeted viral vectors. Nat Commun Feb 10 [Epub ahead of print]. http://www.nature.com/ncomms/2015/150210/ncomms7246/full/ncomms7246.html

The Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines in Langen near Frankfurt/Main, is a senior federal authority reporting to the Federal Ministry of Health (Bundesministerium fr Gesundheit, BMG). It is responsible for the research, assessment, and marketing authorisation of biomedicines for human use and veterinary vaccines. Its remit also includes the authorisation of clinical trials and pharmacovigilance, i.e. recording and evaluation of potential adverse effects. Other duties of the institute include official batch control, scientific advice and inspections. In-house experimental research in the field of biomedicines and life science form an indispensable basis for the varied and many tasks performed at the institute. The PEI, with its roughly 800 staff, also has advisory functions at a national level (federal government, federal states (Lnder)), and at an international level (World Health Organisation, European Medicines Agency, European Commission, Council of Europe etc.). Weitere Informationen:http://www.pei.de

Link:
Precise gene transfer into therapy relevant cells after vector injection into blood

Posted: Wednesday, February 11, 2015, 2:00 AM

(HealthDay News) -- An investigational drug designed to stop Ebola in its tracks has shown early promise in a study involving rhesus monkeys, researchers say.

The drug in question, for now dubbed AVI-7537, appeared to safely protect 75 percent of treated monkeys from Ebola after exposure to the virus. However, it has not been tested in humans, and trials in animals often fail to translate to success in people, experts note.

The search for viable medicines against Ebola has gained urgency as an outbreak in West Africa continues. According to the World Health Organization, by Feb. 9 almost 23,000 cases of Ebola illness have been recorded in Guinea, Liberia and Sierra Leone, including almost 9,200 deaths.

The experimental medication under study is part of the so-called PMO class of drugs, which are designed to attack the genetic code of viruses like Ebola, and short-circuit the ability to reproduce and take hold.

Prior research has already shown that a PMO drug that simultaneously targeted two Ebola genes -- VP35 and VP24 -- provided monkeys with substantial protection against the virus.

But the current study reveals that the VP35 gene is actually a false target, and that a drug aimed solely at the VP24 gene is sufficient to do the job.

"The study demonstrates that we can protect non-human primates from Ebola virus, using only a single . . . agent," study lead author Travis Warren said in a news release from the American Society for Microbiology.

Warren is an investigator at the U.S. Army Medical Research Institute of Infectious Diseases (AMRIID), in Fort Detrick, Md. His team published their findings online Feb. 10 in the journal mBio.

Visit link:
Ebola Drug Shows Promise in Monkey Trial