10 Worst Sources of Aspartame

Aspartate and glutamate act as neurotransmitters in the brain by facilitating the transmission of information from neuron to neuron. Too much aspartate or glutamate in the brain kills certain neurons by allowing the influx of too much calcium into the cells. This influx triggers excessive amounts of free radicals, which kill the cells. The neural cell damage that can be caused by excessive aspartate and glutamate is why they are referred to as “excitotoxins.” They “excite” or stimulate the neural cells to death. Read More.

Knowing the 20 Amino Acids is definitely a MUST for the 2015 MCAT 

Amino acids that are usually negative (i.e. de-protonated) at physiological pH:

- Glutamate (E) Glu, and Aspartate (D) Asp

Amino acids that are usually positive (i.e. protonated) at physiological pH:

- Lysine (K) Lye, Arginine ® Arg 

Histidine is sometimes charged at physiological pH. 

physiological pH = 7, Neutral 

“I WANT THE D!” screams the ribosome “GIVE ME THE D! I NEED THE D NOW!”

A tRNA rushes in and hands over an aspartic acid. 

“WHAT TOOK YOU SO LONG?” yells the ribosome “WERE YOU LOST IN TRANSLATION OR SOMETHING?” it laughs at its own stupid joke

the tRNA doesn’t respond. it’s a piece of nucleic acid for god’s sake. why would it be sentient. 

Study finds brain markers of numeric, verbal and spatial reasoning abilities

A new study begins to clarify how brain structure and chemistry give rise to specific aspects of “fluid intelligence,” the ability to adapt to new situations and solve problems one has never encountered before.

The study, reported in the journal NeuroImage, links higher concentrations of a marker of energy production in the brain with an improved ability to solve verbal and spatial problems. It also finds an association between brain size and number-related problem-solving.

The analysis involved 211 research subjects, making it the largest study to date linking brain chemistry and intelligence in living humans, said University of Illinois postdoctoral researcher Erick Paul, who led the work with research scientist Ryan Larsen and Illinois neuroscience professor Aron Barbey. The work was conducted in the Decision Neuroscience Laboratory at the Beckman Institute for Advanced Science and Technology. More studies will be needed to confirm and extend the findings, the researchers said.

“In our data, we observed two facets of fluid intelligence – one that involves quantitative or numeric reasoning, and another that involves verbal or spatial reasoning,” Paul said. “A similar separation of reasoning abilities has been demonstrated in previous studies.”

The researchers conducted magnetic resonance spectroscopy to analyze brain concentrations of a compound called NAA (N-acetyl aspartate), a byproduct of glucose metabolism and a marker of energy production. They measured brain volume in all subjects using magnetic resonance imaging.

“We found that the quantitative reasoning component of intelligence correlated with brain volume, but not with the concentration of NAA in the brain,” Paul said. “And the verbal and spatial components of intelligence correlated with NAA, but not with brain volume.”

The team observed the same basic relationships when analyzing males and females separately.

The findings add to the evidence that fluid intelligence involves distinct yet interrelated processes in the brain, Paul said.

“Surely there are many things about the brain that determine a person’s intelligence, and the goal is to try to tease apart that puzzle,” he said. “These two brain biomarkers, brain volume and NAA, are each giving us independent information about fluid intelligence. There are different properties of the brain that we can measure, and these different properties go with these different facets of fluid intelligence.”

“Our findings contribute to a growing body of evidence to suggest that intelligence reflects multiple levels of organization in the brain – spanning neuroanatomy, for example brain size, and neurophysiology, such as brain metabolism – and that specific properties of the brain provide a powerful lens to investigate and understand the nature of specific intellectual abilities,” Barbey said.

Antibodies to brain proteins may trigger psychosis

Antibodies defend the body against bacterial, viral, and other invaders. But sometimes the body makes antibodies that attack healthy cells. In these cases, autoimmune disorders develop.

Immune abnormalities in patients with psychosis have been recognized for over a century, but it has been only relatively recently that scientists have identified specific immune mechanisms that seem to directly produce symptoms of psychosis, including hallucinations and delusions.

This ‘immune hypothesis’ is supported by new work published by Pathmanandavel and colleagues in the current issue of Biological Psychiatry. They detected antibodies to the dopamine D2 receptor or the N-methyl-D-aspartate (NMDA) glutamate receptor in a subgroup of children experiencing their first episode of psychosis, but no such antibodies in healthy children. Both are key neural signaling proteins that have previously been implicated in psychosis.

“The antibodies we have detected in children having a first episode of acute psychosis suggest there is a distinct subgroup for whom autoimmunity plays a role in their illness,” said Dr. Fabienne Brilot, senior author on the article and Head of the Neuroimmunology Group at The Children’s Hospital at Westmead in Sydney.

Karrnan Pathmanandavel, Jean Starling, Vera Merheb, Sudarshini Ramanathan, Nese Sinmaz, Russell C. Dale, Fabienne Brilot. Antibodies to Surface Dopamine-2 Receptor and N-Methyl-D-Aspartate Receptor in the First Episode of Acute Psychosis in Children. Biological Psychiatry, 2015; 77 (6): 537 DOI: 10.1016/j.biopsych.2014.07.014

Antibodies to Brain Proteins May Trigger Psychosis

Antibodies defend the body against bacterial, viral, and other invaders. But sometimes the body makes antibodies that attack healthy cells. In these cases, autoimmune disorders develop.

Immune abnormalities in patients with psychosis have been recognized for over a century, but it has been only relatively recently that scientists have identified specific immune mechanisms that seem to directly produce symptoms of psychosis, including hallucinations and delusions.

This ‘immune hypothesis’ is supported by new work published by Pathmanandavel and colleagues in the current issue of Biological Psychiatry. They detected antibodies to the dopamine D2 receptor or the N-methyl-D-aspartate (NMDA) glutamate receptor in a subgroup of children experiencing their first episode of psychosis, but no such antibodies in healthy children. Both are key neural signaling proteins that have previously been implicated in psychosis.

“The antibodies we have detected in children having a first episode of acute psychosis suggest there is a distinct subgroup for whom autoimmunity plays a role in their illness,” said Dr. Fabienne Brilot, senior author on the article and Head of the Neuroimmunology Group at The Children’s Hospital at Westmead in Sydney.

It almost seems like a dirty trick. For decades psychiatrists have administered drugs that stimulate dopamine D2 receptors or block NMDA receptors. These drugs may briefly produce side effects that resemble symptoms of psychotic disorders, including changes in perception, delusions, and disorganization of thought processes. The current findings suggest that people may develop antibodies that affect the brain in ways that are similar to these psychosis-producing drugs.  

“This study adds fuel to the growing discussions about the importance of antibodies targeting neural proteins and it raises many important questions for the field. Do these antibodies simply function like drugs in the brain or do they ‘attack’ and damage nerve cells in some ways?” questioned Dr. John Krystal, Editor of Biological Psychiatry. “Also, are these antibodies producing symptoms in everyone or do they function as a probe of an underlying, perhaps genetic, vulnerability for psychosis?”

Importantly, work is advancing rapidly in this area. Less than a decade ago, anti-NMDA receptor encephalitis was first identified, a disease characterized by inflammation of the brain that causes acute psychiatric symptoms including psychosis. It is commonly misdiagnosed as schizophrenia or bipolar disorder, but is a form of treatable brain inflammation caused by antibodies that attack the brain’s NMDA receptors.

“The data from this study suggests that better interventions are possible, providing hope that major disability can be prevented for the subset of children experiencing acute psychosis with antibodies,” Brilot added. “These findings also contribute significantly to an emerging acceptance in the field of the involvement of autoimmune antibodies in neurological diseases. Combined, these investigations are providing a better understanding of the biology of psychiatric and neurological diseases, as well as pointing to novel treatment approaches for children with these debilitating illnesses.”

First structural views of the NMDA receptor in action will aid drug development

Structural biologists at Cold Spring Harbor Laboratory (CSHL) and Janelia Research Campus/HHMI, have obtained snapshots of the activation of an important type of brain-cell receptor. Dysfunction of the receptor has been implicated in a range of neurological illnesses, including Alzheimer’s disease, Parkinson’s disease, depression, seizure, schizophrenia, autism, and injuries related to stroke.

Led by CSHL Associate Professor Hiro Furukawa, the research team has obtained images of the NMDA (N-methyl, D-aspartate) receptor in active, non-active, and inhibited states. Understanding how NMDA receptors activate is critical in designing novel therapeutic compounds. NMDA receptors are embedded in the membrane of many nerve cells in the brain and are involved in signaling between cells that is essential to basic brain functions, including learning and memory formation.

Structurally, the NMDA receptor is made up of various protein segments, called domains, which together resemble a hot air balloon. The upper, balloon-like portion is comprised of the amino terminal domain (ATD); protruding from the outer surface of the cell is the ligand binding domain (LBD); and the lower, basket-like portion of the receptor, called the transmembrane domain (TMD), drops down inside the cell.

Activation of the NMDA receptor requires binding of brain chemicals called neurotransmitters at specific sites on the LBD. This binding together with structural rearrangement of the ATD triggers the opening of the channel formed by the TMD. This molecular event causes charged atoms called ions flow into the cell. When this occurs in many channels at once, an electrical current is generated that rapidly propagates through the neuron and triggers the release of neurotransmitters. These chemical signals, in turn, bind to receptors on neighboring cells.

Despite accumulating knowledge regarding the structure of the NMDA receptor and its various components, precise, details about the structural movements leading to the process of opening of the ion channel have not been described previously and the mechanism of receptor activation has remained unclear.

In addition to describing the NMDA receptor’s balloon-like structure, Furukawa and the team of CSHL structural biologists have previously revealed many important features of NMDA receptors, including the distinctive ways in which a number of drug compounds attach to the receptor at its various binding sites. “The NMDA receptor architecture itself is quite complicated,” says Furukawa, “but most recently we’ve been really fascinated by how each of its domains moves in a sophisticated but organized manner.”

To learn more about the dynamics of NMDA receptor activation, the researchers combined two molecular imaging techniques, x-ray crystallography and single-particle electron cryomicroscopy, and observed structures of the NMDA receptor in three specific configurations, the activated, non-active, and inhibited states.

Each of these configurations was achieved by the binding of different molecules to the receptor. For example, the activated state required the binding of the neurotransmitters glycine and glutamate, while the binding of the compound ifenprodil resulted in the inhibited state that forces the channel to be closed. The researchers used these molecular structures, published in Nature, to infer how the receptor’s various subdomains rearrange themselves when transitioning from a non-active to the active state.

“With the technology available today, we don’t see continuous movement but instead we see snapshots of NMDA receptors in different functional states,” Furukawa notes.

Superimposing the crystal structure of the NMDA receptor in each of the three functional states revealed which components move—typically by rotating slightly relative to one another—when the ion channel opens. The researchers observed that activation required opening of the bi-lobed architecture of the one of the two ATD subdomains and a reorientation of the ATD as a whole. These changes lead to additional rotations at various points throughout both the ATD and LBD, causing the ion channel pore to open, similar to the opening of a camera shutter.

Furukawa says that studying how components of the NMDA receptor move during activation and inactivation can help scientists create computer simulations to predict how the structures of various drug molecules might impact these movements. “Unless we have a library of molecular structures, people in the field won’t be able to run those simulations,” says Furukawa. “We hope that this new finding will help pharmacologists come up with better therapeutic compounds that have minimal side effects.”

Immuno-Psychiatry: When Your Body Makes Its Own Angel Dust

A new study in Biological Psychiatry reports structural brain damage from an autoimmune encephalitis that impairs behavior in ways that are somewhat similar to the effects of “angel dust”.

The body sometimes makes substances that have effects on the brain in ways that resemble the effects of illicit drugs. In their paper, the authors report findings on a syndrome called anti-NMDA receptor encephalitis that arises when the body makes antibodies that target one of the subunits of the N-methyl-D-aspartate (NMDA) subtype of receptor for the chemical messenger, glutamate.

The antibodies appear to mimic effects produced by the drug phencyclidine (PCP), also known as “angel dust”, which produces a schizophrenia-like syndrome by blocking the NMDA glutamate receptor. Schizophrenia itself is also associated with NMDA receptor dysfunction.

Senior author of the study, Dr. Carsten Finke, Professor at Charité–Universitätsmedizin Berlin, explains, “Anti-NMDA receptor encephalitis is a recently discovered autoimmune disorder of the brain, which causes a severe neuropsychiatric syndrome with behavioral changes, psychosis, memory loss, and decreased levels of consciousness. Although many patients recover well, the majority suffer from long-term cognitive impairment.”

In this issue of Biological Psychiatry, Finke and his colleagues analyzed multimodal magnetic resonance imaging data from 40 patients who were recovering from anti-NMDA receptor encephalitis.

They discovered that the patients had structural damage of the hippocampus and impaired hippocampal microstructural integrity, which strongly correlated with memory performance, disease severity, and disease duration. The hippocampus is a brain structure that plays an important role in memory.

“The results of the study therefore reveal a structural correlate of the persisting memory deficits - the chief complaint affecting daily life of patients after the acute disease stage,” said Finke. “Furthermore, these observations are also in line with evidence that dysfunction of hippocampal NMDA receptors causes severe amnesia.”

These findings suggest that the disease, which can be particularly difficult to quickly diagnose, is critical to treat promptly because the behavioral symptoms can be signs that the antibodies are actively damaging the brain.

“The atypical psychosis syndromes arising from the development of anti-NMDA receptor antibodies are extremely important to diagnosis and treat,” commented Dr. John Krystal, Editor of Biological Psychiatry. “They may be easily misdiagnosed as the psychiatric disorders that they superficially resemble. Nonetheless, these syndromes highlight the importance of NMDA receptor signaling for the genesis of symptoms associated with psychotic disorders.”

Let The Years We’re Here Be Kind (updated: chapter 5)

The realization hit him like a ton of bricks. The moment he thought of it, he deemed himself crazy. He wasn’t.
The scream was coming from the stone itself.
He reached out to place his palms on the surface of the pillar.

aka. the Outlander AU where Fitz is a WWII veteran and Jemma is a healer for the clan Mackenzie

For mrsleopoldfitz​ and engineerleopoldfitz​ as part of thefitzsimmonsnetwork’s “A Whole New World | More Than 5k” Exchange

Unprecedented detail of intact neuronal receptor offers blueprint for drug developers

Biologists at Cold Spring Harbor Laboratory (CSHL) report today that they have succeeded in obtaining an unprecedented view of a type of brain-cell receptor that is implicated in a range of neurological illnesses, including Alzheimer’s disease, Parkinson’s disease, depression, schizophrenia, autism, and ischemic injuries associated with stroke.

The team’s atomic-level picture of the intact NMDA (N-methyl, D-aspartate) receptor should serve as template and guide for the design of therapeutic compounds.

The NMDA receptor is a massive multi-subunit complex that integrates both chemical and electrical signals in the brain to allow neurons to communicate with one another. These conversations form the basis of memory, learning, and thought, and critically mediate brain development. The receptor’s function is tightly regulated: both increased and decreased NMDA activities are associated with neurological diseases.

Despite the importance of NMDA receptor function, scientists have struggled to understand how it is controlled. In work published today in Science, CSHL Associate Professor Hiro Furukawa and Erkan Karakas, Ph.D., a postdoctoral investigator, use a type of molecular photography known as X-ray crystallography to determine the structure of the intact receptor. Their work identifies numerous interactions between the four subunits of the receptor and offers new insight into how the complex is regulated.

“Previously, our group and others have crystallized individual subunits of the receptor – just fragments – but that simply was not enough,” says Furukawa. “To understand how this complex functions you need to see it all together, fully assembled.”

For such a large complex, this was a challenging task. Using an exhaustive array of protein purification methods, Furukawa and Karakas were able to isolate the intact receptor. Their crystal structure reveals that the receptor looks much like a hot air balloon. “The ‘basket’ is what we call the transmembrane domain. It forms an ion channel that allows electrical signals to propagate through the neuron,” explains Furukawa.

An ion channel is like a gate in the neuronal membrane. Ions, small electrically charged atoms, are unable to pass through the cell membrane. When the ion channel “gate” is closed, ions congregate outside the cell, creating an electrical potential across the cell membrane.

When the ion channel “gate” opens, ions flow in and out of the cell through the channel pores. This generates an electrical current that sums up to create pulses that rapidly propagate through the neuron. But the current can’t jump from one neuron to the next. Rather, the electrical pulse triggers the release of chemical messengers, called neurotransmitters. These molecules traverse the distance between the neurons and bind to receptors, such as the NMDA receptor, on the surface of neighboring cells. There, they act much like a key, unlocking ion channels within the receptor and propelling the electrical signal across another neuron and, ultimately, across the brain.

The “balloon” portion of the receptor that Furukawa describes is found outside the cell. This is the region that binds to neurotransmitters. The structure of the assembled multi-subunit receptor complex, including the elusive ion channel, helps to explain some of the existing data about how NMDA receptors function. “We are able to see how one domain on the exterior side of the receptor directly regulates the ion channel within the membrane,” says Furukawa. “Our structure shows why this particular domain, called the amino terminal domain, is important for the activity of the NMDA receptor, but not for other related receptors.”

This information will be critical as scientists work to develop drugs that control the NMDA receptor. “Our structure defines the interfaces where multiple subunits and domains contact one another,” says Furukawa. “In the future, these will guide the design of therapeutic compounds to treat a wide range of devastating neurological diseases.”

Interviewer; David, you've referred to you once as
part of the MTV generation
- what specifically does that mean?

David Garrett; I grew up in a time with many vices,
Consumerism, Internet, TV, etc.
That belongs to everything these days.
That's why I know what young people respond.
Of course, I'm grown up with the tradition
of classical music,but today it makes me just as much fun,
a bit exhaust the possibilities,
and not just to play purely classical.

Aayey kuch abr kuch sharab aayey,
Uske baad aayey jo azaab aayey

let it ascend as
part nimbus, part wine
even if the aftermath is gallows
i shall succumb to it as my shrine

Bam-e-meena sey mahtab utrey,
dast-e-saqi sey aftaab aayey

from the canopy of that carafe
let the silver crescent dive
from the sommelier’s embrace
will my aubade survive

Har rag-e-koon mein phir chiraghan hoen,
Samne phir woh benaqab aayey

once again, every vein
is struck phosphorescent
when the beloved undresses
her veil’s diaphanous lament

Kar raha tha gham-e-jahan ka hisab,
Aaj tum yaad behisab aayey

i was ciphering the bulletins
of these earth-born catastrophes
& today in my memory you were
infinite beyond my own ease

Faiz ki rah sar-ba-sar manzil,
Hum jahan phunchey kamyaab ayey

O Faiz! - every moment is my destination
wherever i reached another destiny was
a home of mine

let it ascend as
part nimbus, part wine

My attempt at loosely translating the behemoth lyricism of Faiz Ahmad Faiz in my mother’s favourite ghazal/poem of his. The lines in itallics are the original urdu verses. 

Dedicated to mi madre - a woman whose very essence is poetry. 

Kizaki Yuria's Ameba Blog - 23\03\2014

I came to think about many things.(・∀・>)

Good evening.

Thanks for your comments
every time!!

And thanks for the many questions!!

I’ll start answering
tomorrow, okay?ヽ(#`・ω・)ノPyuuu

It’s Kizaki Yuria, who finds Manacchan
smiling together with strawberries
to be way too lovely. |ω・ )*glimpse*

We had two Stages today!!

During the first one, we held
the birthday celebration for
our angel Egochan!!

She got the letter
from her best friend Kyonchan.(*・ω・*)

Looks like she turned 14…!!
Ahhhh, how cute she is!! lol

She’s in her 2nd year of middle school,
so she’s pretty much the same age
I had when I joined the group…

She really is everyone’s level headed little sister.

During her Birthday comment
Egochan said this:

“I want to get into the senbatsu”

I feel like it’s been a while
since I last heard these words.

I really want to see
Egochan working hard as
part of the senbatsu.

To do one’s best aiming at the senbatsu…

Which is why the senbatsu
needs to work harder and harder itself!

We should never forget about this…

That’s what I thought.

And the second performance
was Manacchan’s Graduation Stage.

Graduation Stages really are something
you never get used to, no matter
how many times you experience them(>_<)

But I’m really glad that I was
able to see Manacchan’s smile until the very end.

While performing Gyakuten Oujisama
as an under, I was soothed by that
smile countless times…

Her presence alone,
her smile alone is enough
to turn the atmosphere of
Team S’ dressing room
into a gentle one.

And I love
such a Manacchan.

Both fans and us
feel very, very sad and lonely, but…

…if she’ll unchangingly keep having
that smile on her face tomorrow, and the days after…
then that’s all I need to be happy.

Congratulations on your graduation!!

Well then, hoping you
may all sleep peacefully…

Good night Peace!

Good morning Peace!


(Image caption: The N3A receptor, as modeled here by the UB researchers, may be silent under normal conditions, but can be reactivated through the unique site (in red) under acidic conditions, such as after a stroke or seizure)

New finding on elusive brain receptor sheds light on what may kill neurons after stroke

Strokes, seizures, traumatic brain injury and schizophrenia: these conditions can cause persistent, widespread acidity around neurons in the brain. But exactly how that acidity affects brain function isn’t well understood.

In a paper published in March in Scientific Reports, University at Buffalo researchers have begun to unravel some of the puzzle. They found that an elusive brain receptor may play an important role in the death of neurons from neurological diseases.

The UB researchers study a family of brain receptors that are critical to learning and memory, called NMDA (N-methyl-D-aspartate) receptors. They found that one of these receptors called N3A functions through a different mechanism than all other NMDA receptors.

“We found that in contrast to all other NMDA receptors, acidity can reactivate dormant N3A receptors,” said Gabriela K. Popescu, PhD, senior author and professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB. “This insight led us to hypothesize that N3A receptors are silent in normal conditions, which may explain why other researchers have failed to observe them previously.”

Popescu and Kirstie A. Cummings, lead author and doctoral candidate in the UB Department of Biochemistry, found that when the N3A receptors were exposed to acidic conditions, as occurs in brain disorders such as stroke or epilepsy, they reactivate, causing neurons to become more sensitive to the neurotransmitter glutamate, which can, under certain circumstances, kill them.

The research was done in cell culture with recombinant receptors.

“Given that acidity increases after a stroke or an epileptic seizure, reactivation of N3A receptors may be one reason why neurons die after these neurologic events,” said Popescu. “So finding ways to prevent acidification or the reactivation of N3A receptors may prevent brain damage from strokes or seizures, for example.”

She added that N3A proteins appear to be more abundant in brains of people with schizophrenia. “This is in line with our findings, since schizophrenia, a disease associated with high acidity in the brain, causes brains to shrink,” she said.

Popescu noted that the finding also sheds much needed light on the N3A receptors. “Since their discovery more than 20 years ago, attempts to understand the roles of N3A receptors in the brain have been unsuccessful,” she said. “Because many labs have failed to record N3A activity from neurons, some researchers even began to doubt their relevance to brain activity.”

The new paper reveals that electrical currents passed by N3A receptors can excite cells in response to acidity, which makes them different from all other NMDA receptors.

The researchers have identified the site on the receptor where acidity acts to reactivate these receptors, a different location from the site where acidity acts to inhibit all other NMDA receptors.

“This site is new and unique and thus can be used to make drugs that are very specific to the N3A receptor,” said Popescu.

more random MedDRA terms
  • 貧血 ひんけつ anaemia
  • アナフィラキシー様反応 アナフィラキシーようはんのう anaphylactoid reaction 
  • 血管浮腫 けっかんふしゅ angioedema 
  • アスパラギン酸アミノトランスフェラーゼ増加 アスパラギン さんアミノトランスフェラーゼぞうか aspartate aminotransferase increased 
  • 血中尿素増加 けっちゅうにょうそぞうか blood urea increaed 
  • 血中アルカリホスファターゼ増加 けっちゅうアルカリホスファターゼ ぞうか blood alkaline phosphatase increased 
  • 骨髄機能不全 こつづいきのうふぜん bone marrow failure 
  • 気管支痙攣 きかんしけいれん bronchospasm 
  • 心不全 しんふぜん cardiac failure 
  • 便秘 べんぴ constipation 
  • 脳血管発作 のうけっかんほっさ cerebrovascular accident

Alzheimer’s disease drug-development pipeline: few candidates, frequent failures


Alzheimer’s disease (AD) is increasing in frequency as the global population ages. Five drugs are approved for treatment of AD, including four cholinesterase inhibitors and an N-methyl-D-aspartate (NMDA)-receptor antagonist. We have an urgent need to find new therapies for AD.


We examined, a public website that records ongoing clinical trials. We examined the decade of 2002 to 2012, to better understand AD-drug development. We reviewed trials by sponsor, sites, drug mechanism of action, duration, number of patients required, and rate of success in terms of advancement from one phase to the next. We also reviewed the current AD therapy pipeline.


During the 2002 to 2012 observation period, 413 AD trials were performed: 124 Phase 1 trials, 206 Phase 2 trials, and 83 Phase 3 trials. Seventy-eight percent were sponsored by pharmaceutical companies. The United States of America (U.S.) remains the single world region with the greatest number of trials; cumulatively, more non-U.S. than U.S. trials are performed. The largest number of registered trials addressed symptomatic agents aimed at improving cognition (36.6%), followed by trials of disease-modifying small molecules (35.1%) and trials of disease-modifying immunotherapies (18%). The mean length of trials increases from Phase 2 to Phase 3, and the number of participants in trials increases between Phase 2 and Phase 3. Trials of disease-modifying agents are larger and longer than those for symptomatic agents. A very high attrition rate was found, with an overall success rate during the 2002 to 2012 period of 0.4% (99.6% failure).


The database demonstrates that relatively few clinical trials are undertaken for AD therapeutics, considering the magnitude of the problem. The success rate for advancing from one phase to another is low, and the number of compounds progressing to regulatory review is among the lowest found in any therapeutic area. The AD drug-development ecosystem requires support.

Full Article

(Image: Shutterstock)