Watching a human navigate like a bat is impressive

Daniel Kish, who lost his eyesight to cancer, is now an expert in echolocation - the technique that a bat uses to navigate at night. This is why he is sometimes known as the real life Batman - although Daredevil would be more accurate. Using these skills Daniel is able to enjoy independence and freedom from many of the constraints that might inhibit him otherwise.

Daniel locates objects in his environment by clicking his tongue and interpreting the echoes that this returns. In fact his sense of visualisation is so strong that he can detect the exact location, size and even density of his surroundings.

Daniel's story has been around for a while but there have been some positive developments - he is now teaching echolocation to other blind people and the results are truly amazing.

ORIGINAL: Sploid

By Omar Kardoudi

Ingenious. Fixing a body’s broken genes is becoming possible

IT SOUNDS like science fiction, and for years it seemed as though it was just that: fiction. But the idea of gene therapy—introducing copies of healthy genes into people who lack them, to treat disease—is at last looking as if it may become science fact.

The field got off to a bad start, with the widely reported death of an American liver patient in 1999. In 2003 some French children who were being treated with it for an immune-system problem called SCID developed leukaemia. Since then, though, things have improved. Indeed one procedure, for lipoprotein lipase deficiency (which causes high levels of blood fats, with all the problems those can bring), has been approved, in Europe, for clinical use.

The most recent success, announced last month in the Lancet, was of an experimental treatment for choroideremia, a type of blindness. This is caused by mutation of the gene for a protein called REP1. Without REP1, the eye’s light receptors degenerate. Robert MacLaren of Oxford University used a virus to deliver working versions of the REP1 gene to the most light-sensitive part of the retina. Five of the six participants in the trial duly experienced an improvement in their sensitivity to light. Two were so improved that they could read more letters than previously on a standard eye chart.

Dr MacLaren’s work complements that of Albert Maguire and Jean Bennett at the University of Pennsylvania, who use gene therapy to treat another eye disease, Leber’s congenital amaurosis. A defective version of a gene called RPE65 means that, in this condition, retinal cells are starved of vitamin A, which also causes blindness. Putting normal copies of RPE65 into the retina leads, as with REP1, to greater light sensitivity and—sometimes—clearer vision.

Drs MacLaren, Maguire and Bennett all use adeno-associated viruses (a type not known to cause illness, and which does not much provoke the immune system) to carry their genetic payloads to the target. Luigi Naldini of the San Raffaele Telethon Institute for Gene Therapy, in Milan, employs a rather scarier vector—one derived from HIV, the virus that causes AIDS—because its life cycle involves it integrating its genes into its host cells’ nuclei.

Last year Dr Naldini and his colleagues reported that, using their safely neutered version of HIV, they had inserted working copies of genes into blood stem cells which lack them, in order to treat metachromatic leukodystrophy (which damages nerves) and Wiskott-Aldrich syndrome (which harms the immune system and reduces blood’s ability to clot). In both cases—though in only a handful of patients, for the diseases are rare—Dr Naldini’s approach either prevented the disease or at least halted its progress.

The rarity of metachromatic leukodystrophy, Wiskott-Aldrich syndrome and many other diseases for which gene therapy might be appropriate means a lot of the applications of this approach are narrow. But a different one—constructing tailored genes and using them to guide the immune system—may have wider application, specifically against cancer.

Michel Sadelain, of the Memorial Sloan-Kettering Cancer Centre, in New York, is one of those at the forefront of a method that works this way. It employs chimeric antigen receptor (CAR) cells, which are engineered versions of T-cells, the part of the immune system that kills body cells, including tumorous ones, which have become threats.

Dr Sadelain’s trick is to take natural T-cells from patients (specifically, leukaemia and lymphoma patients) and add to them genes which turn those cells’ attention to the tumour in question, causing them to seek out its cells and destroy them. He then returns the modified cells to the patient, where they multiply and attack.

The CAR pool

The extra genes in CAR cells are derived in part from monoclonal-antibody genes. These have, in turn, been selected for their affinity to the target tumour. Because CAR cells multiply in the body this is, as Dr Sadelain puts it, like creating a living drug.

Last year Dr Sadelain’s team, and also another group led by Carl June at the University of Pennsylvania, published results showing the promise of CAR cells in treating people with acute lymphoblastic leukaemia. Dr Sadelain’s paper showed that they caused full remission in all five adult patients treated (though two subsequently died of complications, one set of which was unrelated to the treatment); Dr June’s, that they eradicated the cancer from two children. And, at a meeting of the American Society of Hematology held in December, both researchers reported further successes.

There is, moreover, one further technique that might bring gene therapy into the mainstream. Current approaches work by adding genes to affected cells. But it may be possible to modify those cells’ existing, broken genes, using a method called CRISPR-Cas9 editing, a process that takes advantage of a natural antiviral system which chops up genetic material.

CRISPR-Cas9 editing is specific to particular sequences of genetic letters, and can thus be tweaked to do a researcher’s bidding. In a recent edition of Cell, Sha Jiahao of Nanjing Medical University showed how to use it to execute the reverse of gene therapy—creating genetic problems, rather than solving them—in monkeys. His aim was to produce model organisms that might help understanding of diseases in human beings (though making such models out of monkeys is controversial). But the technique might eventually be employed to do running repairs on damaged DNA in people.

That, if it ever happens, is a long way off. In the meantime, the promise of gene therapy can be seen in the fact that it is attracting lawyers. The University of Pennsylvania has licensed its CAR technology to Novartis, a Swiss drugs firm. The pair of them are now fending off a lawsuit brought by competitors including Juno Therapeutics, the creation of three research centres of which Memorial Sloan-Kettering is one. For patients, that suggests gene therapy really is something worth fighting over.

From the print edition: Science and technology



ORIGINAL: The Economist

From the print edition

Feb 8th 2014

Teenage Girl Develops App to Help the Blind

“The fact that I’m the only girl interested in my high school going to these hackathons is really sad. Maitreyee Joshi, senior at Lynbrook High, has a deep passion for building technologies that help the physically and mentally disabled people.

“The fact that I’m the only girl interested in my high school going to these hackathons is really sad". 

Maitreyee Joshi, senior at Lynbrook High, has a deep passion for building technologies that help the physically and mentally disabled people.

For example, while working at Stanford Research Labs, she built a head controlled quadcopter in order to facilitate movement for her professor’s mute quadriplegic friend. Also, for last year’s science fair project, she wrote an biclustering algorithm that found DNA mutations that caused a brain tumor called Glioblastoma Multiforme.

Currently, Maitreyee is focusing her attention on the blind. With the popularity and spur of iPhone apps being developed, she thought over the summer of how she could use the same to build a systemized technology for the blind. It wasn’t long till she was able to build an iPhone game app that helped blind people develop their spatial skills and navigate through new environments. Testing it out with the blind proved to be a surprised. After playing the game only twice they were able to map out the entire building they were in.

It was with this that Maitreyee knew that she was onto something, and decided that she would develop it further along. Maitreyee is a rarity amongst other girls in her high school in which she is an aspiring tech engineer and interested in things like robotics and hackathons. Although, she is aware that being interested in tech has that nerdy connotation, Maitreyee is thankful that she goes to a high school which is academically focused and welcomes similar and more students like her.

But, as she has admitted several times, the experience of being sometimes the only girl interested in tech in her high school can be quite frustrating.

“I wish that I had more friends that are girls that can come along with me to these hackathons. Most of the time I’m with a group of guys all the time, which can get really annoying and sometimes drive you away.”

Maitreyee also recalls a similar experience when she was working on a robotics club in school.

“I would have loved it if the girls on the team were more actively involved in things other than public relations or marketing.”

However, with women like Marissa Mayer and Sheryl Sandberg, Maitreyee is excited at the prospect of being the only femgineer in her high school, which she believes makes her unique and a crusader as well.

“I feel like I’m a fighter going against social conventions, which excites me.”

As Maitreyee begins to scale her iPhone app. she is beginning to learn early lessons and dilemmas that other engineers in startups face which is stepping outside the building.

Before finding success with testing out the app with blind people, Maitreyee was showing signs of disinterest and was continually doubting that the app would work at all. What made it even worse was that she had a meeting with one of the Accessible Technology instructors at the Silicon Valley Blind Center.

“I was scared about showing him my prototype, and that it wouldn’t be good enough.”

Maitreyee was so scared that she canceled the meeting and then again for the second time.

“I’ve always felt that it wasn’t ready enough, if I had a bit more time to fine-tune, work out the logic, and fix the bugs then it would be fine.”

After a couple of weeks it was time again to meet and present the prototype.

“That night I really wanted to cancel. But I knew that it was starting to get out of control and that I couldn’t keep canceling these meetings.”

Summing up all her courage she decided just to go with it.

Nervously presenting her prototype, Maitreyee was shocked that he enjoyed it when they were testing it out.

Maitreyee Joshi. Volunteer Position: Web Content Specialist.
EducateHaitiNow

“As he went through his thought process and described a verbal layout of the building, I was starting to get excited and thinking that this may actually just work.”

The meeting was just the push that Maitreyee needed to take on the development further.

In hindsight, she knew that she had exaggerated the situation and was stuck in a cycle of thinking that the prototype was never good enough, which she regrets. Asking what advice she would give to others engineers who get stuck in the same cycle of thinking, she replied “Just face your fears, push yourself to go outside, take the leap, and just do it!”


To follow Maitreyee progress you can visit her website at

http://www.maitreyeejoshi.com/

Sources: Femgineer

Chemical makes blind mice see

ORIGINAL: Berkeley

By Robert Sanders, Media Relations | July 25, 2012

BERKELEY —

Mice with a genetic disease that causes blindness regained some sight after injection with a chemical “photoswitch.” The eye of the untreated mouse on the left shows no response to light, while the pupil of the mouse on the right, which was injected with the chemical, contracts in light.

Mice with a genetic disease that causes blindness regained some sight after injection with a chemical “photoswitch.” The eye of the untreated mouse on the left shows no response to light, while the pupil of the mouse on the right, which was injected with the chemical, contracts in light.

A team of University of California, Berkeley, scientists in collaboration with researchers at the University of Munich and University of Washington, in Seattle, has discovered a chemical that temporarily restores some vision to blind mice, and is working on an improved compound that may someday allow people with degenerative blindness to see again.

The approach could eventually help those with retinitis pigmentosa, a genetic disease that is the most common inherited form of blindness, as well as age-related macular degeneration, the most common cause of acquired blindness in the developed world. In both diseases, the light sensitive cells in the retina — the rods and cones — die, leaving the eye without functional photoreceptors.

The chemical, called AAQ, acts by making the remaining, normally “blind” cells in the retina sensitive to light, said lead researcher Richard Kramer, UC Berkeley professor of molecular and cell biology. AAQ is a photoswitch that binds to protein ion channels on the surface of retinal cells. When switched on by light, AAQ alters the flow of ions through the channels and activates these neurons much the way rods and cones are activated by light.

“This is similar to the way local anesthetics work: they embed themselves in ion channels and stick around for a long time, so that you stay numb for a long time,” Kramer said. “Our molecule is different in that it’s light sensitive, so you can turn it on and off and turn on or off neural activity.”

Because the chemical eventually wears off, it may offer a safer alternative to other experimental approaches for restoring sight, such as gene or stem cell therapies, which permanently change the retina. It is also less invasive than implanting light-sensitive electronic chips in the eye.

“The advantage of this approach is that it is a simple chemical, which means that you can change the dosage, you can use it in combination with other therapies, or you can discontinue the therapy if you don’t like the results. As improved chemicals become available, you could offer them to patients. You can’t do that when you surgically implant a chip or after you genetically modify somebody,” Kramer said.

“This is a major advance in the field of vision restoration,” said co-author Dr. Russell Van Gelder, an ophthalmologist and chair of the Department of Ophthalmology at the University of Washington, Seattle.

Kramer, Van Gelder, chemist Dirk Trauner and their colleagues at UC Berkeley, the University of Washington, Seattle, and the University of Munich will publish their findings Thursday, July 26, in the journal Neuron.

The blind mice in the experiment had genetic mutations that made their rods and cones die within months of birth and inactivated other photopigments in the eye. After injecting very small amounts of AAQ into the eyes of the blind mice, Kramer and his colleagues confirmed that they had restored light sensitivity because the mice’s pupils contracted in bright light, and the mice showed light avoidance, a typical rodent behavior impossible without the animals being able to see some light. Kramer is hoping to conduct more sophisticated vision tests in rodents injected with the next generation of the compound.

“The photoswitch approach offers real hope to patients with retinal degeneration,” Van Gelder said. “We still need to show that these compounds are safe and will work in people the way they work in mice, but these results demonstrate that this class of compound restores light sensitivity to retinas blind from genetic disease.”

From optogenetics to implanted chips

The current technologies being evaluated for restoring sight to people whose rods and cones have died include injection of stem cells to regenerate the rods and cones; “optogenetics,” that is, gene therapy to insert a photoreceptor gene into blind neurons to make them sensitive to light; and installation of electronic prosthetic devices, such as a small light-sensitive retinal chip with electrodes that stimulate blind neurons. Several dozen people already have retinal implants and have had rudimentary, low vision restored, Kramer said.

Eight years ago, Kramer, Trauner, a former UC Berkeley chemist now at the University of Munich, and their colleagues developed an optogenetic technique to chemically alter potassium ion channels in blind neurons so that a photoswitch could latch on. Potassium channels normally open to turn a cell off, but with the attached photoswitch, they were opened when hit by ultraviolet light and closed when hit by green light, thereby activating and deactivating the neurons.

Subsequently, Trauner synthesized AAQ (acrylamide-azobenzene-quaternary ammonium), a photoswitch that attaches to potassium channels without the need to genetically modify the channel. Tests of this compound are reported in the current Neuron paper.

New versions of AAQ now being tested are better, Kramer said. They activate neurons for days rather than hours using blue-green light of moderate intensity, and these photoswitches naturally deactivate in darkness, so that a second color of light is not needed to switch them off.

“This is what we are really excited about,” he said.

Coauthors with Kramer, Van Gelder and Trauner are UC Berkeley current or former post-docs or graduate students Aleksandra Polosukhina, Jeffrey Litt, Ivan Tochitsky, Ivan De Kouchkovsky, Tracy Huang and Katharine Borges; and post-doctoral fellow Joseph Nemargut and ophthalmology resident Yivgeny Sychev at the University of Washington.

The work was supported by the National Eye Institute of the National Institutes of Health (EY018957 & EY003176) and Research to Prevent Blindness.

RELATED INFORMATION

Photochemical Restoration of Visual Responses in Blind Mice (July 26, 2012 Neuron)

“Blind” cells see the light; maybe someday humans will, too (Nov. 2004 press release)

Richard Kramer laboratory Web site