Groundbreaking progress has been made in the fight against spinal muscular atrophy (SMA). American researchers have developed a gene therapy that enabled mice bearing the disease to overcome the most severe symptoms.

SMA is the most common neuromuscular disease in newborn children. It leads to loss of neuromuscular control caused by the degeneration of the spinal cord neurons. As a consequence, signals from the brain no longer get translated into movement. The pathological condition causing this is a decrease in the level of a protein called survival motor neuron (SMN). The disease leads to a wasting of muscles, with problems in swallowing, breathing and moving and often ends in premature death.  So far no treatment has been developed however, researchers have engineered model SMA in mice, where the level of SMN reflects that of the human condition.

Researchers based in Ohio state university have now used gene therapy based on viruses to deliver the SMN protein to defect cells in the spinal cord. The therapy was based on an adeno-associated viral vector that had been depleted for all viral genes. The empty virus shell was used to shuttle a more active version of SMN into diseased neurons. The therapy lead to a normal lifespan of the treated mice and restored a nearly normal motor function. It was also shown that when the therapy is given directly after birth it has the greatest effect.

The researchers conclude that this therapy might demonstrate a unique opportunity for a successful therapy of SMA affected children.

http://www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt.1610.html

Researchers at the Ludwig-Maximilian University (LMU) in Munich have developed a new model for type II diabetes, by engineering a strain of transgenic pigs bearing a partially inactive version of a receptor which regulates the glucose uptake from the blood stream.

Diabetes is a disease where the sufferers have very high levels of glucose in the blood stream. This is caused either by the absence of insulin production in the body (diabetes type I) or an inherited or accomplished resistance against the action of insulin (diabetes type II). As a result, glucose taken in by nutrition is not get stored as glycogen in the muscles but is left in the blood stream, leading to a chronic high level blood glucose. Cases of type II diabetes are rapidly increasing in the developed world and are predicted to reach 370 million by the year 2030 worldwide. Side effects like heart attacks and stroke cases put a tremendous strain on health care systems. So far no model to study the disease in detail has been available.

The team from the LMU used genetic modification to create a strain of pigs, which develops several essential symptoms of type II diabetes. Insulin is produced in the pancreas, stimulated by two proteins from the small intestine: the glucose-dependent insulin-releasing peptide (GIP) and glucagon-like peptide 1 (GLP-1). The transgenic pigs have a partially inactive version of the GIP receptor. As a result, secretion of insulin from the pancreas is very low and the cells producing it are sparser than in normal animals. Both effects increase with age which resembles the human condition. As physiology and metabolism of pigs is very similar to those in humans, this model system has the potential for translational studies on diabetes type II.

http://diabetes.diabetesjournals.org/content/early/2010/02/23/db09-0519.abstract

Researchers in Germany have successfully predicted the layout of self-assembling molecules on a surface.

In the search for new technology such as molecular electronics and novel catalysis systems, the ability to control the behaviour of surfaces is key. Surfaces can be covered in a 'designed' layer of molecules, but a more scalable approach is to use the intrinsic physical traits of the molecules themselves: for particular types of molecules and surfaces, the molecules can self-assemble in a regular and reproducible fashion. A jigsaw puzzle where the pieces fall into place by themselves.

These self-assembled monolayers can be measured at atomic resolution and analysed with computational methods and are quite well understood. The challenge to making an application lies in the next step: how to predict the structure, given a known surface and molecule? This is a harder problem because while an experiment automatically gives rise to a 'stable' structure, a computational calculation will have to search through all possible structures, calculate their energy, find the low energy stable stuctures and from there deduce what will be observed in an experiment. It is like knowing how the pieces of a jigsaw are shaped, but not knowing what the completed picture will be.

In this piece of work, the researchers used 'dendron' molecules which are V-shaped and interact well with graphite surfaces. This system exhibits a wide variety of self-assemblied structures. Experimentally, several forms nicknamed 'sawtooth', 'honeycomb', 'jigsaw', 'tiretrack' and 'wave' have been observed. Independently, computational simulations have generated the same structures. Moreover, the predicted relative stabillity and the most stable structure agrees well with experimental observations.

The predictive power is particularly impressive considering that simplified model was used of the molecule; the model assumes the molecule to be a V-shape with several interaction sites to the surface. This appers to be sufficient, in this case, to capture the physical traits of the system and give accurate predictions. It is forseen that other molecular jigsaws that could be simplified in this way, could also use this predictive model to generate useful results.

Researchers at the Babraham Institute have, for the first time, demonstrated that T cells, a type of white blood cell that plays a central role in the body's immune response, can be tailor-made.

Active T cells, developed in the thymus from a complex cocktail of biochemical signals and intracellular genetic changes, are akin to the body's security surveillance system, detecting and administering to viruses and infections.  As we age, the thymus shrinks, producing fewer T cells. This is a normal occurrence that has little effect on healthy bodies. However, in individuals with HIV/AIDS, chemo/radiotherapy and bone marrow transplants, the body's ability to replace T cells is severely compromised, leaving us with fewer, less diverse cells patrolling our immune system and putting us at greater risk of infection.

The international team of academic and industrial immunologists, have discovered that a group of signaling proteins, called Phosphoinositide 3-kinases (PI3KS), known to transmit signals from external receptors to the inside of the cell, have multiple  signalling functions involved in the creation of T-cells. One signalling molecule, called PI3K-p110g, carries signals from a receptor known as CXCR4, which then binds to the chemokine CXCL12 that is produced in the thymus. When isolated from the thymus, T cells could continue their developmental program if cultured in the presence of CXCL12, bringing scientists one step closer to the ideal of full T cell development without feeder cells.

Besides progressing invitro T cell development, this discovery could also be valuable in clinical settings, where uncontaminated T cells are needed for transplantation and regenerative medicine.

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