New research tries to ‘calm down’ stressed B-cells in-order to treat diabetes

The cycle of inflammation. B cells communicate via cytokines with other inflammatory cells, such as T cells and macrophages, to maintain and amplify the cycle of inflammation (http://www.roche.com/pages/downloads/photosel/061106/html/detail_3.html)

Diabetes is a major global health problem. In the USA alone there are some 25.8 million people living with the disease. Diabetes costs the US healthcare system more than $200 billion dollars each year. It’s a problem that is likely to further explode in the next few years. Consequently new treatments are of the upmost importance.

There are two types of diabetes: type 1 and 2. The hormone insulin is a major player in the development of the disease. Insulin has an important role in the body and works alongside glucagon to regulate blood sugar.  The most common is type of diabetes is type 2 (90-95% of cases). It is caused by insulin insensitivity and eventual loss of insulin production in the pancreas.

Diabetes is highly related to stress. New research has discovered a key molecule that works to amplify this stress early on the diabetes process. This molecule is called thioredoxin-interacting protein (TXNIP). It is central to the inflammation process and leads to the death of insulin secreting B cells in the pancreas.

B cells can be thought of as the factories of the pancreas producing vast amounts of insulin every minute. Great fact:

“There are a billion or so beta cells in the average healthy pancreas. These cells will make more copies of insulin every year than there are grains of sand on every beach and in every desert in the world”

 B cells and every other cell rely on an organelle called the endoplasmic reticulum (ER). This organelle works to package, tag and dispatch all the proteins, including insulin, from the cell. Diabetes comes about when the ER becomes stressed and faulty (maybe due to the need to overproduce insulin). When this occurs proteins are not packaged properly and accumulate within the B cell. The body’s response to this malfunction is drastic; it effectively destroys the cell. It does this by activating the interlukin-1 (IL-1) pathway and therefore inducing apoptosis.

This in its self is not as bad as it sounds, because our bodies have B cells in reserve. However when it does occur, our B cells will have to work harder and become more stressed. Therefore the problem propagates and the chance of developing diabetes is increased.

TXNIP is involved in the exacerbation of the IL-1 pathway and cell apoptosis. Current studies are looking into IL-1 targeting, however new research has shown that TXNIP is a very central player in the stimulation of the IL-1 pathway. Therefore if you remove TXNIP from the equation you will save B-cells from apoptosis and in theory protect the body form developing diabetes. This has been shown by the researchers to occur in mouse models. Consequently this idea is being translated and tested in up coming clinical trails. The hope is that by shutting down TXNIP we will prevent cell stress and hopefully delay or stop the onset of diabetes. However my question is surely TXNIP has a natural role in the body, by shutting it off are we not in danger of loosing its benefits? What do you think about this new development?

The Alzheimers timeline, enabling early diagnosis and better treatment

Alzheimer’s disease predominantly affects people of an older age. However new research suggests that signs of Alzheimer’s can be seen up to 25 years before the expected onset of the disease.

Scientist have been studying families with a genetic risk of the disease. 128 people were studies, all with a 50% chance of inheriting one of three mutations that will cause the disease Alzheimer’s. The genetic form of Alzheimer’s will normally hit much earlier, 30’s – 40’s, than the more general form which affects people in their 60’s.

How unlocking the genome has kick started a new medical era

Personalised medicine is all about you, who you are, what you have experienced and what you are made up of. In the year 2000, after 10 years of hard work, a working draft of the human genome was announced. This draft consisted of the identification and mapping of around 20,000 -25,000 genes. The identification and “decoding” of the human genome opened the door to a new breed of medical practise; personalised medicine.

New cell sorting method will be ‘music’ to researchers’ ears.

A new development in cell analytics uses sound waves to sort cells. This researchers say will lead to the development of miniaturised medical diagnostic devices.

This new device utilises a set of acoustic tweezers. These are generated from the projection of two sound waves across a silicone membrane. These tweezers can be used to sort a continuous flow of cells into 5 or more channels. This sorting can be altered through adjusting the frequency of the acoustic waves.

Cell sorting devices are in a serious need of a revamp. Currently they are bulky, expensive and have the potential to damage cells. The technology is also limited because it can only sort cells into two channels over one step. This new method will change all this, creating efficient and miniaturised cell sorting devices. The aim is to produce a cell sorter that is the same size as a mobile phone; this could be used for blood or genetic tests.

The acoustic cell-sorting device uses a layer of silicone (polydimethylsiloxane) with two parallel transducers placed either side of the chip. These transducers convert alternating current into acoustic waves. These waves interfere with each other and by doing so form pressure nodes (channels) on the chip. Cells are then channelled towards these pressure nodes. The important point is that these transducers are tuneable. This allows different frequencies to be produced across the chip, allowing for different channels to be created.

To test the device a stream of fluorescent polystyrene beads were sorted into three channels. Before switching on the transducer the particles were not filtered. However as soon as it was the beads were separated into 3 distinct channels. The device was then used to sort human white blood cells, which were affected by Leukaemia, into five channels. A possible of 10 channels has been suggested as possible by the researchers.

This provides researchers with a serious advance in their ability to sort cells. Utilising a novel method to sort cells will enable researchers to work with greater flexibility. It is also more convenient, efficient and safer. Are there any other new technological advances that are exciting you?

Did you hear – New research shows stem cells to be effective in treating deafness

A recent study has shown that introducing stem cells into the inner ear could be a new potentially effective treatment for deafness. Hearing depends upon the ear being able to convert sounds waves into electrical signals; this allows the brain to translate the waves into meaning.  Specialised tiny hairs deep within the inner ear use vibrations, caused by sound waves, to create electrical nerve signals. 1 in 10 people who suffer from severe hearing loss are not able to carry out the translation of sound waves to electrical signals. This is because the nerve cell, called the spiral ganglion neurons, are damaged and no longer respond to hair vibrations.

Hair cells in the inner ear

The aim of the research is to replace these cells with new functioning cells. Therefore allowing hearing to recover. The study used gerbils to carry out the experiment due to the similarity in their hearing and humans. Pluripotent stem cells were taken from a human embryo. These were grown in a chemical medium designed to control their development and develop them into spiral ganglion cells. These cells were then delicately injected into the inner ears of 18 deaf gerbils.

The study was conducted over 10 weeks and on average 45% of the treated gerbils had a significant increase in their hearing capability. The improvement would be like going from not being able to hear a lorry in the street to the point where you could hear a conversation. Although not a complete cure the implications for a death person could be huge. About 1/3 of the gerbils responded well to treatment, some regained 90% of their hearing. However 1/3 barely responded at all. The hearing measurements were made by measuring brainwaves, this however was only carried out for a period of ten weeks. If the treatment were to be attempted in humans, it would have to be shown to work for a much greater duration.

This is hugely encouraging study. However it will be a long time until we see this sort of therapy done in humans. One of the major drawbacks is that getting the cells into a human ear will pose a much more significant challenge. A second draw back for this technique is that it wont hep the vast majority of people who suffer from hearing loss. This is because the majority of hearing problems occur due to damage to the tiny hairs within the ear. The research group had also reported the ability to form tiny hairs from the same stem cells. However many in the field believe this technique to be close too impossible to carry out. This is because the hair cells would have to be placed very exactly and this would be extremely hard to do.

Success for gene therapy in treating spinal muscular atrophy

Spinal Muscular atrophy (SMA) is the leading genetic cause of infantile death in the world. It is a rare genetic disease, which occurs in 1 in 6000 children. These children often die young because there is currently no cure for SMA. Children with SMA are missing a protein called Survival motor neuron-1 (SMN1). SMN1 directs nerves in the spine and gives commands to muscles.

A study at the university of Missouri recently found that SMA could be treated using gene therapy. The team used a viral vector, expressing full length SMN1 cDNA, to introduce the missing gene into a mouse’s nervous system. Therefore allowing SMN1 to be expressed within the nervous system and restore ‘normal’ function.

The introduction of the missing gene increased the mouse’s lifespan to 10-25 days when compared to 5 or 6 days for untreated mice. The researchers admit the system is far from perfect but say the experiment shows promising results in our ability to rescue the nervous system in SMA.

Importantly this treatment has a real application for human patients suffering from SMA. Clinical trials for SMA gene therapy are likely to begin within the next 12-18 months. Hopefully researchers can build on the success of this study and refine and develop the gene therapy process so it is more effective. This is a positive step in the field of gene therapy and offers a window of hope for those suffering from various genetic disorders. What do you think? How could this research be used for other genetic disorders? What are the major barriers to gene therapy?

Hope for Huntington’s

Huntington’s Disease affects key areas of the brain

Two recently identified regulatory proteins may hold the key to success for the treatment of Huntington’s disease (HD) and other neurodegenerative diseases. These proteins appear to play a critical role by clearing away misfolded proteins, which accumulate in neurons affected by HD. The findings help to explain some of the fundamental causes of this untreatable disease. The study also provides ‘clear’ therapeutic targets, which cold be utilised to treat HD.

HD is a genetic disorder that occurs in 6-7 persons per 100,000. It is characterised by progressive deterioration of: involuntary movement control, cognitive decline and psychological problems. This is all caused by a mutation in the htt gene. This mutation results in the accumulation of the misfolded htt protein within certain cells of the nervous system. Currently there is no cure or effective treatments. Consequently these results are hugely encouraging.

The first of these regulatory proteins is PGC-1alpha. This protein helps regulate the creation and operation of mitochondria. It does this by regulating mitochondrial transcription factors. This regulation is important because neurons are ‘all about energy’. This is because they have such a huge demand for it. It has been previously shown that the mutant htt gene interfered with normal levels of PGC-1alpha. This study went onto to show this to be correct. It also showed, in a mouse HD model, elevated PGC-1alpha levels virtually eliminated problematic misfolded htt proteins.

Specifically PGC-1alpha is vital in mitochondrial autophagy. Autophagy is essential because neurons must last a lifetime. Therefore recycling old and dangerous parts of the neuron limits dangerous oxidative molecules, produced during metabolism. PGC-1alpha drives this autophagy pathway through transcription factors EB or TFEB. TFEB is a relatively newly discovered player, however it is emerging as a leading actor in HD. It was shown that even without the induction of PGC-1alpha, TFEB could prevent the aggregation of htt and subsequent neurotoxicity.

 In their experiments the scientists crossbred HD mice with mice that produced elevated levels of PGC-1alpha. The offspring consequently showed a dramatic improvement in their HD progression. Neuronal degeneration was not observed and neurons did not die, like they would under normal circumstances. These two regulatory proteins, PGC-1alpha and TFEB, provide 2 new therapeutic targets for HD. They utilise two key areas bioenergetics and protein quality control to allow neurons to function properly. By utilising these regulatory proteins neuronal function can be maintained and accumulation of misfolded proteins prevented. This is great news for HD because it has so often been seen as a lost cause. The next important steps will be to develop ways to exploit these molecules further and develop therapeutic options utilising these molecules in humans. What do you think about this topic? Are we going to see a breakthrough in HD treatment? How long would it take to develop?