neurodudes

Personal genomics is just starting and this talk gives a preview of what one of the first companies is doing to bring this to market, though the field is starting to heat up with some competition.

Surprising facts from the video:

1. 23andme co-founder Anne Wojcicki is married to Google co-founder Sergei Brin
2. Data portability is already available. According to the video, users can download the raw data from the 580,000 SNP array and do whatever they want with it.
3. The SNP array is 580,000 SNPs! Wow. I assumed that the number of genetic features was on the order of 100-1000, giving a rough haplotype.
4. Sharing/Web 2.0 features: The real power is 23andwe, an effort to data mine and leverage the power of a large database with many people’s genetic information. The founders mention that they want to contribute back to science and healthcare by surveying their customers behaviors and medical issues to uncover further correlations with genes. Like Facebook, the service becomes more valuable and more informative as the network grows.

Description of the talk from Google:

The 23andMe Personal Genome Service offers customers a glimpse at their own DNA sequence, a 750-megabyte string that functions as the operating system for a human being. Common variations in this code can influence the structure and function of the associated wetware in predictable ways. Some of these variations and their effects on traits such as athletic talent, pain sensitivity and avoidance of errors will be discussed in reference to three well-documented examples.

I didn’t notice this before, but in a study of about 4000 subjects, people who took Rimonabant (marketed as Acomplia), a selective antagonist of the cannabinoid type 1 receptor (CB1), apparently had a 3.2% incidence of depressive disorders where placebo-takers apparently had a 1.6% incidence. Also, irritability went from .6% to 1.9%, parasomnia from .2% to 1.5%, nervousness from .2% to 1.2%, sleep disorders from .4% to 1.0%, memory loss from .9% to 1.6%, hypoesthesia from .6% to 1.6%, and sciatica from .4% to 1.0%. Psychiatric adverse events were dose-dependent.

(more…)

Happy Labor Day (US)! Topping the NYT most popular articles list right now is an interesting article about a new schizophrenia treatment that targets certain glutamate receptors unlike previous dopaminergic drugs. The drug, which is being developed by Eli Lilly, is partially due to this interesting observation:

For decades, psychiatrists have known that users of PCP, a street drug sometimes called angel dust, have symptoms nearly identical to those of people with schizophrenia. By the 1980s, scientists had discovered that PCP blocked brain receptors that are triggered by an amino acid called glutamate. This led some companies and scientists to study ways to stimulate glutamate receptors as a treatment for schizophrenia.

But the brain has many different kinds of glutamate receptors, and figuring out how to stimulate or block them in medically beneficial ways has proved complicated. Instead of focusing on the receptors blocked by PCP, Dr. Schoepp concentrated on modulating the action of glutamate receptors in the brain’s prefrontal cortex, an area responsible for personality and learning.

(more…)

There’s a nice NRN review on the many recent papers on therapeutic use of transcranial magnetic stimulation.

Is there a future for therapeutic use of transcranial magnetic stimulation?

The past year has seen the publication of a remarkable number of papers about the potential therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in conditions ranging from cocaine addiction to stroke and depression. Are we witnessing the discovery of a miraculous cure-all or will this bubble burst like the magnetotherapies of the Victorian era1? We argue below that there is good evidence that rTMS can produce after-effects on the brain, and that these translate into effects on simple behaviours. However, the rationale for applying the same methods to treat disease is in many cases unclear.

The MIT Media Lab is holding a conference on May 9th, “Human 2.0: New Minds, New Bodies, New Identites” which will launch a number of new initiatives centered around the goal of inventing a better future via direct engineering of the human. Amongst these things will be the initiation of the MIT Center for Human Augmentation, and the launch of a number of novel applied Neurotechnology Projects.

Guest speakers on May 9th will include MIT professors (Roz Picard, Hugh Herr, myself, etc.) and many acclaimed speakers such as Oliver Sacks and John Donoghue. Registration may be close to being full, but it will be webcast.

More information at:
http://h20.media.mit.edu

- Ed

Brain stimulation and depression has been one of the hot topics of the last decade. Now, a Washington Post story suggests that at least some of this may be overrated, at least for the NeuroStar Transcranial Magnetic Stimulation (TMS) device from Neuronetics:
A novel machine designed to treat depression by zapping the brain with magnetic pulses shows no clear evidence of working, federal health advisers concluded Friday.

A clinical trial of the device provided results that, in one analysis, suggested it’s no better than sham treatment, according to FDA documents.”

Going to be a long slog. TMS *has* been approved for treating depression in Canada and Israel, for the company NeoPulse.

Transcranial magnetic stimulation (TMS) is a popular technology for stimulating human cortical neurons, due to its safety, noninvasiveness, and efficacy. A TMS device is just a little coil of wire, through which 10,000 Amps of current is cranked during a period of only a few hundred microseconds; the resultant rapidly-changing magnetic field induces eddy currents in the brain. Depending on the protocol used, TMS can drive/inhibit a region of cortex corresponding to roughly a cubic centimeter or two, and is being explored for the treatment of depression, the reduction of auditory hallucinations during schizophrenia, and the alleviation of tinnitus and migraines. Thousands of papers on medicine and psychology have been written using this tool.

Yet the device itself is expensive and rare — they can run from $20,000 to $50,000 or even more, despite the fact that they are, in essence, a coil, a switch, a bank of capacitors, and a power supply. Much of the art lies in making the devices safe and fail-proof. Is it possible to hack/engineer a system that is safe, fault-tolerant, efficacious, and inexpensive? And furthermore, can we facilitate a community that will devise such devices, and share information about protocols and approaches to brain hacking?

This past August at Foo Camp, a hackers’ conference in Northern California, a group of people got together and set out to do just that. We are designing a safe, noninvasive, modular, and “open source” brain stimulator that will open up the field of circuit modulation to a wider audience. Members of the group include therapists and mental health professionals, engineers, programmers, and others interested in either the development of such devices, or the sharing of information on this front. Key to the design is safety — we want to make sure that the devices we create are as safe as devices on the market. Also, all the information is released under the Creative Commons “Attribution and Sharealike” license. This is a new model for “open source” medical device development — which may move it beyond the domain of simply creating “cool toys,” and to creating real devices.

You can find out more information, or contribute to the project, or learn from the project, at
http://transcenmentalism.org/OpenStim/

-Ed

{alpha}-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson’s Models — Cooper et al., Science

Fascinating evidence pointing toward a treatment for parkinson’s. Basically, Lindquist’s group finds that overexpression of a trafficking protein Rab1 that moves folded proteins from the ER to the Golgi can prevent alpha-synuclein accumulation-triggered death of rat neurons.

Of course, in vitro is not in vivo. And, for all we know, Parkinson’s could be a complex, multi-mechanism disease. But this looks promising!

Abstract:

Alpha-synuclein misfolding is associated with several devastating neurodegenerative disorders including Parkinson’s Disease (PD). In yeast cells and in neurons {alpha}Syn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following {alpha}Syn expression in yeast was a block in endoplasmic reticulum (ER) to Golgi vesicular trafficking. In a genome-wide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab GTPase Ypt1p, which associated with cytoplasmic {alpha}Syn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against {alpha}Syn-induced dopaminergic neuron loss in animal models of PD. Thus synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.

An Anti-Addiction Pill? - New York Times

Lots of interesting stuff here on new treatments for addiction, including: A methadone (heroin-substitute) replacement called buprenorphine with less dependency and less of a high; an injectible version of alcoholism treatment naltrexone called Vivitrol, which is injectable and lasts one month; some medications that increase GABA production; and, perhaps most innovative is a vaccine against nicotine that allows antibodies to bind nicotine and prevent crossing through the blood-brain barrier.

Excerpts with some of the neat experiments involving dopamine receptors and environmental factors in addiction are after the jump.
(more…)

Doctors Struggle to Treat Mysterious and Unbearable Pain - New York Times

Hadn’t heard about this before:

[...] she felt a sudden pop in her hamstring. “It felt like a guitar string had been plucked and it had broken,” said Ms. Toussaint, who is now 45.

An intense burning sensation followed; it felt as if her leg had been doused in gasoline and set on fire, she said. The next day, the college athletics trainer determined that she had pulled her hamstring. But even years later, the pain would not subside. It migrated to her other leg, leaving her bedridden for nearly a decade, and overtook her vocal cords, leaving her temporarily mute.

All the while, doctors puzzled over and even doubted her mysterious condition.

Ms. Toussaint now knows that she is among an estimated one million Americans living with complex regional pain syndrome, a nerve disorder formerly known as reflex sympathetic dystrophy syndrome. For patients with the disorder, a trauma as mild as a fractured wrist or a twisted ankle can cause the nerves to misfire, so much so that intense pain messages are constantly sent to the brain.

Interestingly, neural stimulation only provides a short-term benefit with eventual adaptation. In some cases, ketamine administration (enough to put the patients in a temporary coma) has completely stopped the pain. Ketamine is an anesthetic (although it has been known to actually stimulate circulation at certain doses) with well-known psychedelic properties. It is also a non-competitive NMDA antagonist that is often used in conjunction with traditional opiods for an analgesic effect.

I wonder if this effect is simply due to the interaction with the NMDA receptor or is something more complex. (For example, the analgesic effects of ketamine when combined with a opiods seem unrelated.)

Here’s a link to the original paper in the journal Pain, which suggests that CRPS patients have suffered damage to small-diameter PNS nociceptive fibers.