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How scientists are identifying new preventive measures and cures for diseases using latest technologies

People wonder how scientists identify new preventive measures for diseases. My reply to them is - by creatively connecting various things.

For instance, a percentage of people carry genetic mutations for certain diseases. While several of these people go ahead and develop diseases for which they have mutated genes, interestingly, a small number of people don't develop them. The reasons are unknown till now. Scientists are guessing the reasons, though. But if you study these reasons scientifically and apply them to all the others who have the potential to develop the diseases, they can be prevented! That is smartness!

If you want to develop therapies for prevention, if you want to come up with ways of not just finding the cause, but also ways of preventing the manifestations of disease, then these individuals may help find a solution. We now have mechanisms that allow us to search for people who should have gotten sick but didn't.

In a recent study, a group of researchers looked at the genetic data of about 589,000 people. The information came from 12 previously collected data sets. The researchers wanted to see if, among these people, there were any individuals who remained healthy despite carrying certain genetic mutations linked to severe childhood disorders.

The researchers focused on diseases that are caused by mutations in a single gene, and have severe symptoms that generally show up early in childhood.

In their search, the investigators found three adults who did not have cystic fibrosis, despite having mutations on both copies of the CFTR gene, which normally causes the condition, according to the study, published on April 11, 2016 in the journal Nature Biotechnology (1).

Three other adults identified in the study lacked a certain form of a skeletal condition called atelosteogenesis, despite carrying mutations on both copies of the gene called the SLC26A2 genethat is linked with the disorder. Atelosteogenesisis usually lethal at birth, or shortly afterward.

Other people in the study lacked conditions such as familial dysautonomia (which affects nerve cells, and can result in sudden death during childhood), Smith-Lemli-Opitz syndrome (which causes widespread developmental problems throughout the body), and epidermolysis bullosa simplex (a severe skin condition), despite having mutations in the genes for these conditions.

This maybe because these individuals also have other genes that somehow suppress these disease-causing mutations, preventing these people from getting sick, said study co-author Rong Chen, director of clinical genome informatics at the Icahn Institute of Genetics and Multiscale Biology in New York.

These people who don't develop the diseases despite the mutations for the diseases in their genes can provide several clues for disease prevention.

Today, medicine recognizes more than 5,000 genetic diseases caused by mistakes in DNA, and the majority of these illnesses have no cure or treatments. These are the diseases that stand to benefit most from genomic medicine, and specifically, the newest and most powerful genome-editing technology, called CRISPR.

It was initially found that these CRISPR sequences were used by bacteria to ward off predatory viruses. Scientists who observed this in Nature, are now trying to mimic the same procedure to edit and fix harmful mutated genes to control diseases.

CRISPR uses an enzyme called Cas9, a programmable molecular machine that binds to a small, guide RNA-molecule in cells. Together, these components hone in on target genes and carry out precise molecular "surgery" to create a genetic change. This can be used to correct a defect that causes a genetic disease.

CRISPR has taken the research community by storm, because it can make DNA changes in many different settings and many different kinds of cells. Scientists can now much more rapidly and comprehensively investigate what different genes do and how they work together.

Scientists have arrived at a watershed moment in their understanding of genomic science. Not only have researchers identified many of the mutations that cause a variety of diseases, but now there is also a technology that could create new medicines that directly target and correct those mutations (2).


2. How scientists are crossing the blood-brain barrier (BBB) to deliver drugs... 

BBB is a semipermeable membrane separating the blood from the cerebrospinal fluid, and constituting a barrier to the passage of cells, particles, and large molecules. The blood–brain barrier allows the passage of water, some gases, and lipid-soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial to neural function. On the other hand, the blood–brain barrier may prevent the entry of lipophilic(fat-loving), potential neurotoxins  by way of an active transport mechanism mediated by P-glycoprotein.

But this makes it difficult for certain drugs to enter the brain to cure neurodegenerative diseases like Parkinson's. Doctors often have to inject drugs directly into the brain, an invasive approach that requires drilling into the skull.

Some scientists have had minor successes getting intravenous drugs past the barrier with the help of ultrasound or in the form of nanoparticles, but those methods can target only small areas and can have side effects. Now neuroscientist Viviana Gradinaru and her colleagues at the California Institute of Technology show that a harmless virus can pass through the barricade and deliver treatment throughout the brain.

Gradinaru's team turned to viruses because the infective agents are small and adept at entering cells and hijacking the DNA within. They also have protein shells that can hold beneficial deliveries, such as drugs or genetic therapies. To find a suitable virus to enter the brain, the researchers engineered a strain of an adeno-associated virus into millions of variants with slightly different shell structures. They then injected these variants into a mouse and, after a week, recovered the strains that made it into the brain. A virus named AAV-PHP.B most reliably crossed the barrier.

Next the team tested to see if AAV-PHP.B could work as a potential vector for gene therapy, a technique that treats diseases by introducing new genes into cells or by replacing or inactivating genes already there. The scientists injected the virus into the bloodstream of a mouse. In this case, the virus was carrying genes that encoded green fluorescent proteins. So if the virus made it to the brain and the new DNA was incorporated in neurons, the success rate could be tracked via a green glow on dissection. Indeed, the researchers observed that the virus infiltrated most brain cells and that the glowing effects lasted as long as one year. The results were recently published in Nature Biotechnology.

3. How Universal cancer vaccine is 'found'...

Recently Scientists have taken a “very positive step” towards creating a universal vaccine against cancer that makes the body’s immune system attack tumours as if they were a virus.

Writing in Nature, an international team of researchers described how they had taken pieces of cancer’s genetic RNA code, put them into tiny nanoparticles of fat and then injected the mixture into the bloodstreams of three patients in the advanced stages of the disease.

The patients' immune systems responded by producing "killer" T-cells designed to attack cancer.

The vaccine was also found to be effective in fighting “aggressively growing” tumours in mice.

Such vaccines are fast and inexpensive to produce, and virtually any tumour antigen [a protein attacked by the immune system] can be encoded by RNA.

The nanoparticulate RNA immunotherapy approach introduced here may be regarded as a universally applicable novel vaccine class for cancer immunotherapy.

Three patients were given low doses of the vaccine and the aim of the trial was not to test how well the vaccine worked. While the patients' immune systems seemed to react, there was no evidence that their cancers went away as a result. 

In one patient, a suspected tumour on a lymph node got smaller after they were given the vaccine. Another patient, whose tumours had been surgically removed, was cancer-free seven months after vaccination.

The third patient had eight tumours that had spread from the initial skin cancer into their lungs. These tumours remained “clinically stable” after they were given the vaccine.

The vaccine, which used a number of different pieces of RNA, activated dendritic cells that select targets for the body's immune system to attack. This was followed by a strong response from the "killer" T-cells that normally deal with infections.

Cancer immunotherapy is currently causing significant excitement in the medical community.

It is already being used to treat some cancers with a number of patients still in remission more than 10 years after treatment.

While traditional cancer treatment for testicular and other forms of the disease can lead to a complete cure, lung cancer, melanoma, and some brain and neck cancers have proved difficult to treat.

Being able to inject an effective treatment into a patient’s bloodstream would be a significant step forward. The vaccine also produced limited flu-like side-effects in contrast to the extreme sickness caused by chemotherapy.

This new study, in mice and a small number of patients, shows that an immune response against the antigens within a cancer can be triggered by a new type of cancer vaccine.

Although the research is very interesting, it is still some way away from being of proven benefit to patients.  

In particular, there is uncertainty around whether the therapeutic benefit seen in the mice by targeting a small number of antigens will also apply to humans, and the practical challenge of manufacturing nanoparticles for widespread clinical application.

However, more research is needed in a larger number of people with different cancer types and over longer periods of time before we could say we have discovered a ‘universal cancer vaccine’. But this research is a very positive step forwards towards this global goal.


1. R. Chen et al. Analysis of 589,306 genomes identifies individuals resilient to sev...Nature Biotechnology. Published online April 11, 2016. doi:10.1038/nbt.3514. 


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