Tomorrow is Today

Gene Therapy Cures Diabetes in Dogs in SIngle Treatment

Five lucky diabetic beagles have been cured of their canine type 1 diabetes using gene therapy, according to research published in the February issue of Diabetes.

Researchers from Barcelona’s Universitat Autonoma previously found the therapy effective in treating mice, but this is the first time gene therapy — when a patient’s DNA is supplemented or changed to treat a disease — has proven successful in curing diabetes in large animals.

Gene therapy encodes a functional gene to replace a mutated one, or inserts DNA that produces a therapeutic protein to treat a disease. In this case, the dogs were injected with two extra genes that together form a “glucose sensor” that can regulate glucose uptake and reduce excessive glucose levels in the blood.

Four years later, the dogs that received both genes had no symptoms of diabetes and stabilized glucose levels. They recovered a normal body weight and didn’t exhibit any secondary complications.

(via Gene Therapy Cures Diabetic Dogs In Only One Shot | Popular Science)

Rewiring the Brain: Gene Therapy Makes Mature Neurons Change Type 

The cerebral cortex—the gray matter that forms the outer layers of the mammalian cerebrum and cerebellum—is divided into six different layers based on the presence of specialized neurons…

Denis Jabaudon is interested in using the tools of modern biology to understand the genetic mechanisms that establish and maintain those layers. Over the past few years, his lab has published papers implicating various genes in the generation of specific neuronal subtypes.

Now they have gone a step further. They have developed a new electrochemical method to transfer genes into specific types of neurons—they call it iontoporation. Using it, they have transformed one type of neuron in a mature brain into a different type entirely…

[This research] tells us something about the ability of a mature brain to adapt to being rewired. Although Jabaudon and others have made some headway in working out how the different neurons arise, they still don’t know how plastic they are—if they can change fates after they started differentiating down one particular path.

In the context of brain injury, it would be useful to know if certain neural circuits could be reprogrammed and repaired by having the neurons that are already present change fates to adapt to the damage. But this has been challenging to determine, because changing the fate of specific neurons in the latter stages of differentiation has been technically difficult.

(via Reshaping the brain: scientists reprogram neurons after birth | Ars Technica)

First Gene Therapy to be Commercially Available in the West Coming in 2013

Gene therapies carry a lot of promise, including the ability to treat any number of inherited diseases that have few treatment options. They are a way to literally tinker with the fundamental material that tells our cells how to function, so their potential is indeed vast—if we can make them work.

Glybera will treat lipoprotein lipase deficiency (LPLD), an extremely rare inherited disorder affecting the metabolism of certain fat particles. It affects something like one or two people in a million… Gene therapy is still limited to single-gene disorders—and most common diseases are more complex multi-gene problems.

Still, the acceptance of the first gene therapy into Western medicine could mark a turning point for gene medicine, provided nothing goes wrong. Many labs are still working on gene therapies for a number of conditions, and uniQure itself is working on additional genetic therapies for everything from hemophilia to Parkinson’s. Even limited success there would naturally be a huge leap forward for medical science.

(via The West’s First Gene Therapy Goes On Sale Mid-2013 | Popular Science)

Researchers Manipulate Shape of Nanoparticles to Deliver Gene Therapy Without Viruses

Researchers from Johns Hopkins and Northwestern universities have discovered how to control the shape of nanoparticles that move DNA through the body and have shown that the shapes of these carriers may make a big difference in how well they work in treating cancer and other diseases.

This study is also noteworthy because this gene therapy technique does not use a virus to carry DNA into cells. Some gene therapy efforts that rely on viruses have posed health risks.

“These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine,” said Hai-Quan Mao, an associate professor… in Johns Hopkins’ Whiting School of Engineering.

(via Shape coding replaces risky viruses in DNA nanoparticle therapy | KurzweilAI)

‘Maternal Gene’ Discovered: Complex Behaviors Traced to Specific Gene in a Specific Set of Neurons

Researchers from The Rockefeller University in New York found that mice engineered to suppress the gene spent less time licking, nursing and retrieving their pups compared with a control group.

The findings… suggest the single gene could be responsible for motivating mothers to protect, feed and raise their young, the scientists said.

Previous studies have found that a brain region called the medial preoptic area controls aggression, sexual receptivity and maternal care in mice. In the new study, scientists artificially lowered the levels of the chemical in the medial preoptic area of female mice, to examine how they functioned without it.

They found that the mice spent less time caring for their pups but that their levels of aggression remained unchanged. Dr Ana Ribiero, who led the study, said: “The main finding of this paper is manipulation of a specific gene in a specific group of neurons (nerve cells) can drastically alter the expression of a complete, biologically crucial behaviour.” The effects were “remarkably specific” to maternal care because even related behaviours, such as aggression, remained unchanged, she added.

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Viral Gene Therapy Repairs Damaged Neurons in Mice, Restores Sense of Smell

To re-engineer the mice, scientists led by Jeffrey Martens programmed a cold virus with normal IFT88 genes and infected the animals with it. The virus did what viruses do, invading the mouse’s cells and replicating. This inserted the new DNA sequence into the mice, which in turn caused the cilia to re-grow from the ends of the olfactory neuron. This had a notable effect on the appetites of the mice — after just two weeks, the mice increased their body weight by 60 percent. The scientists put some smelly substances in front of the animals and noticed their neurons were firing as they should. “At the molecular level, function that had been absent was restored,” Martens said in a news release.

(via Viral Gene Therapy Gives Non-Smelling Mice the Ability to Smell | Popular Science)

Researchers Experimenting With Mutant HIV In Anti-Cancer Gene Therapy

As HIV replicates, it creates slightly new versions of itself over successive generations — this allows it to readily resist most of the drug cocktails and anti-viral treatments developed to fight it. But it could also allow HIV to serve as a sort of molecule factory, creating new iterations of compounds that work in slightly different ways.

The CNRS team modified the genome of HIV by inserting a human gene for a protein called deoxycytidine kinase (dCK). This protein is found in all cells and is important for activating anti-cancer drugs. Researchers would like to make a more potent form of dCK that would allow cancer drugs to work more effectively, which could in turn require less of them, causing fewer side effects and less toxicity.

The team multiplied this mutant HIV through several generations, yielding an entire library of mutant dCK proteins, about 80 in all. Ultimately, they found a variant that induces tumor cells to die. With just 1/300th the dose of cancer-killing drugs, this one-two protein punch is just as effective at stopping tumor growth.

This is notable for a few reasons — first, the mutated protein was shown to work in human cell cultures, eliminating several middle steps with bacteria or animals. Second, it suggests there’s a way to make cancer drugs work more effectively simply by beefing up the body’s internal chemistry. And finally, it suggests a new therapeutic use for one of humanity’s strongest adversaries — HIV-derived protein factories could pump out generations upon generations of new molecules and drug compounds to help alleviate a wide range of illnesses.

(via AIDS Virus Could Be Harnessed to Fight Cancer | Popular Science)

Clinical Trials For Anti-Blindness Gene Therapy Coming in 2013

Retrosense is developing a treatment in which other cells in the retina could take the place of the rods and cones, cells which convert light into electrical signals. The company is targeting a group of neurons in the eye called ganglion cells. Normally, ganglion cells don’t respond to light. Instead, they act as a conduit for electrical information sent from the retina’s rods and cones. The ganglion cells then transmit visual information directly to the brain.

Doctors would inject a non-disease causing virus into a patient’s eye. The virus would carry the genetic information needed to produce the light-sensitive channel proteins in the ganglion cells. Normally, rods, cones, and other cells translate light information into a code of neuron-firing patterns that is then transmitted via the ganglion cells into the brain. Since Retrosense’s therapy would bypass that information processing, it may require the brain to learn how to interpret the signals. 

So far, Retrosense and its academic collaborators have shown that the treatment can restore some vision-evoked behaviors in rodents. The treatment also seems safe in nonhuman primates. The optogenetically modified ganglion cells of these primates are light-responsive, but behavioral tests aren’t possible, as there are no nonhuman primate models of retinal degeneration, says Retrosense CEO Sean Ainsworth.

(via Company Aims to Cure Blindness with Optogenetics - Technology Review)

New Technique Converts Adult Blood Cells into Stem Cells

[We already know that it is possible to turn red blood cells into stem cells]: Viruses can be harnessed to set the clock back on the cells by delivering genes to them, but that can come with complications, like mutated genes or cancer.

Instead, this technique (just published in PLoS One uses plasmids, DNA rings that replicate inside cells, then degrade. By jolting the cells with an electrical pulse, researchers created tiny holes holes in the cells that the plasmids could slip through.

The plasmids then inserted genes that cause the red blood cells to change to induced-pluripotent stem cells, or iPS—embryonic-like cells that act as if they were part of a 6-day-old embryo.

Unlike other processes, the cells were also introduced into a simulated version of the bone marrow environment they’re usually in. Early reports from the researchers say it’s been successful.

Usually, scientists might be able to eke out a handful of usable stem cells out of hundreds. The Johns Hopkins team has reported that their process can make up to 50 or 60 percent of them usable, without introducing viruses. But the next step for the researchers is the important test: checking the sturdiness of the cells by seeing what they can develop into after the stem cell phase.

(via Scientists Turn Adult Red Blood Cells Into Embryonic Stem Cells | Popular Science)

New Technology Delivers RNA Interference Therapy Directly to the Brain

RNAi therapy involves researchers producing snippets of RNA, a close relative of DNA, that match a portion of a gene of interest. When administered, this so-called small interfering RNA (siRNA) causes the destruction of that gene’s products before it can be turned into a protein.

The specificity of RNAi for targeting particular genes has attracted a lot of interest from people who want to use it as a clinical treatment. “Today’s platforms target the protein that causes the disease and bind to that protein. We stop the protein from being made in the first place,”

…But a recurring challenge for the therapeutic RNAi field is how to deliver the siRNAs to the right place in the body. On their own, the small molecules do not survive long in the bloodstream, so simply injecting a patient with a solution of unprotected siRNAs is not effective.

“The key technical hurdle is getting the siRNA [inside] the right cells,” says Greene. For several of its projects, Alnylam uses nanoparticles to protect and deliver its siRNAs, which can then be delivered by injection.

But for genetic diseases that originate in the brain, the body’s own defenses, namely the blood-brain barrier, complicate delivery further. To circumvent the blood-brain barrier, which prevents most molecules from leaving the bloodstream and entering the brain, Alnylam has looked to a different delivery mechanism: direct dosing of unpackaged siRNAs.

(via Gene Control, Delivered Directly to the Brain - Technology Review)