U.S. PATENT OFFICE ANNOUNCES 'PATENTS FOR HUMANITY' PROGRAM

In an effort to promote the use of patented technologies for humanitarian purposes, the U.S. Patent and Trademark Office (USPTO) recently announced the launch of a new pilot program entitled 'Patents for Humanity'.  This program invites patent owners and licensees to compete on the basis of how they have used patented technologies to address significant public health or quality of life issues, particularly in poor countries around the globe.  Four categories of technologies will be considered: medical technology, food and nutrition, clean technology, and information technology.  Winners will receive certificates from the USPTO for the accelerated processing of specific patent-related matters.

The program advances the president’s global development agenda by rewarding companies who bring life-saving technologies to underserved people of the world, while showing how patents are an integral part of tackling the world's challenges.

Highlighting success stories of humanitarian engagement that are compatible with business interests and strong patent rights will demonstrate how businesses can effectively contribute while maintaining commercial markets.

Businesses of all sizes and forms, as well as universities and other not-for-profit entities, are encouraged to apply.  Additional details can be found at http://www.uspto.gov/patents/init_events/patents_for_humanity.jsp; applications will be accepted beginning on March 1, 2012.

[USPTO]

EMBRYONIC NEURONAL GROWTH GUIDED BY SMALL NUMBER OF PROTEINS

In an effort to understand how growing motor neurons migrate successfully toward their eventual muscular targets during embryonic development, a team of researchers led by Sam Pfaff of the Salk Institute has discovered that this highly specific process appears to be guided by just a small number of genes and the corresponding proteins they encode.  These proteins somehow attract or repel the axon of the growing neuron, thereby guiding the neuron in the direction in which it should grow, and dictating whether this growth should continue or stop.  According to Pfaff:

"We focused on motor neurons that control muscle movements, but the same kind of thing is going on throughout embryonic development of the entire nervous system, during which millions of axons make trillions of decisions as they move to their targets".

It is hoped that these findings may lead to a better understanding of ALS and other neurodegenerative diseases that are characterized by defective nerve cell functioning, and potentially of various cancers as well.

[Salk Institute for Biological Studies]

ALZHEIMER’S RESEARCH GAINS ADDITIONAL SUPPORT FROM U.S. GOVERNMENT

In keeping with the federal government’s goal of having an effective treatment for use against Alzheimer’s disease by 2025, the National Institutes of Health announced yesterday that it will devote an additional $50 million this year to dementia research, in addition to the $450 million per year that it currently spends on research in this arena.  Additionally, President Obama plans to ask Congress next week to commit an additional $80 million in new funding for Alzheimer’s research in 2013, which would bring total funding to over half a billion dollars.

Various patient advocates and government advisors do not believe this figure to be sufficient, noting that far more funding is devoted to research into other chronic diseases, and that a significantly greater sum is necessary to ensure meaningful results:

At a meeting last month, some of the government's own Alzheimer's advisers said it could take a research investment of as much as $2 billion a year to make a real impact. "Our country cannot afford not to make these commitments," Alzheimer's Association President Harry Johns told that meeting.

However, this action is generally seen as a positive sign: 

"There is no doubt that there is commitment that needs to be applauded here," added Eric J. Hall, president of the Alzheimer's Foundation of America.

Given the current economic climate, it is difficult to predict whether the Congress will approve additional funding.  In the interim, it is encouraging to see that the NIH is increasing its support for this vital area of research, and that the President is apparently devoted to this effort.

[MSNBC]

NEW FINDINGS REGARDING TAU PROTEIN PROVIDE INSIGHT INTO ALZHEIMER'S PATHOGENESIS

To date, a thorough understanding of how Alzheimer’s develops and progresses has remained elusive.  It has long been thought that a protein known as 'tau' is directly involved in Alzheimer's pathogenesis, but the specific role of tau has not been well understood.  Tau protein is present within the brain of individuals who do not have Alzheimer’s, and in this context appears to promote the healthy functioning of neurons.  However, abnormal forms of tau protein aggregate inside cells within the brains of individuals suffering from Alzheimer’s, forming the ‘neurofibrillary tangles’ that are characteristic of the disease. 

Last week, The New York Times announced that two different research studies have generated important findings indicating that tau may be responsible for the spread of Alzheimer's disease throughout various regions of the brain.  In one of these studies, which was led by Karen Duff and colleagues of Columbia University’s Taub Institute for Alzheimer’s Disease Research, researchers observed that, over time, ‘tau pathology’ (or ‘tauopathy’) does not arise independently within different regions of the brain; instead, it spreads from its initial site within the brain’s entorhinal cortex to neurons within other regions of the brain, directly through the synaptic connections between individual neurons.  While the mechanisms underlying this are not yet well understood, the researchers note that these findings - published in the open-access journal PLos One - provide a great deal of insight into Alzheimer's pathogenesis, demonstrating that:

AD progresses via an anatomical cascade as opposed to individual events occurring in differentially vulnerable regions.  [PLos One]

The New York Times describes a second study, soon-to-be-published in the journal Neuron, conducted by a team of researchers led by Bradley T. Hyman of the Alzheimer’s Disease Research Center at Massachusetts General Hospital.  Like Duff et al., these researchers observed that, over time, abnormal tau protein spreads from the entorhinal cortex to other regions within the brain via some sort of direct neuronal connection, rather than arising independently within each region - thereby representing the pathway by which Alzheimer's spreads throughout the brain.  It therefore can be postulated that agents capable of blocking this pathway may be effective in blocking the progression of Alzheimer's disease. 

Additional findings regarding the potential role that tau protein may play in Alzheimer’s have been generated by a third team of researchers.  Led by Rakez Kayed of the University of Texas Medical Branch at Galveston, and reported in the FASEB Journal, these researchers have determined that an intermediate form of tau appears to be more highly toxic than either single units of the protein or the larger neurofibrillary tangles.  These intermediates are comprised of ‘tau oligomers’; that is, aggregates of a small number of individual units of tau protein.  Also referred to as ‘prefilamentous tau aggregates’, these oligomeric intermediates are found in significantly greater levels within the Alzheimer’s brain than in healthy brains.  The researchers conclude that these tau oligomers - which ultimately join together to form neurofibrillary tangles - appear to represent the most highly toxic entities associated with the progression of Alzheimer's disease, and therefore may represent important therapeutic targets.

THANK YOU, DR. OLNEY

The University of California, San Francisco announced yesterday that neurologist and pioneering ALS researcher Richard K. Olney, MD, has passed away.  Dr. Olney began focusing on ALS, also known as 'amyotrophic lateral sclerosis' or 'Lou Gehrig's disease', approximately 25 years ago, ultimately serving as the founding director of UCSF's ALS Treatment and Research Center.  The Center currently sees more than 375 patients with ALS and conducts considerable research with the goal of developing an effective treatment for the disease, which afflicts approximately 1 of every 1,000 individuals, with a median survival time of three to five years.

Dr. Olney's life - and now, his death - is of particular note, given his life's work:  Dr. Olney himself was diagnosed with ALS eight years ago.

Rather than stepping aside, Dr. Olney continued his work until the very end, even though he ultimately had little control over muscle function and was able to communicate only via a computer tablet which translates eye blinks into words.

The impact of his life is recalled by Lucie Bruijn, Chief Scientist with the ALS Foundation, which supported much of his work:

“He has been an inspiration to those of us who work every day toward the goal of finding meaningful therapies for ALS. It is an honor to have known him personally and the ALS Association is proud to have funded his important studies to identify genetic and environmental influences that impact the disease.”

Dr. Olney, we salute you.  May your life's work continue to bear much fruit, and may you continue to inspire the researchers, and patients and families, who are battling this horrible disease.  Like you, we look forward to the day when a cure is found.

[University of California, San Francisco]

THE NATIONAL INSTITUTE OF MENTAL HEALTH: SHORT-TERM PRIORITIES AND LONG-TERM GOALS

In his most recent 'Director's Blog', National Institute of Mental Health (NIMH) Director Thomas Insel comments on the conflicting priorities that have been voiced by the Institute's advisory council regarding the types of research programs that should be funded by the NIMH:

"Some advisors want more funds in services research; other advisors want more funds in basic neuroscience. Some are thinking of the immediate needs; others are focused on the paradigm shifts that may be revealed by another decade of research."

There is clearly a need for both short-term needs and long-term goals to be addressed, but this is quite challenging particularly at a time when the NIMH budget is constrained.  Dr. Insel concurs that programs that encourage the implementation of evidence-based practices and ensure access to currently available treatments should certainly be supported by the NIMH, as these will address the very real needs that currently exist.  At the same time, he suggests that this short-term focus must be balanced with an investment in neuroscience research that will provide a better understanding of the brain and various mental disorders, with the goal that this will, in time, result in the development of truly novel and highly effective treatments against these disorders:

"In many cases patients receiving the best of current care are not recovering. We can blame the mental health care system, the absence of insurance or providers, or stigma, but the inconvenient truth is that our treatments are not good enough. NIMH has a critical role for ensuring that more effective medications, devices, and psychosocial treatments are available in the future."

In short, Dr. Insel argues that, while short-term objectives must not be ignored, long-term goals will be met only if fundamental discovery science receives significant support from the NIMH.  We will hope that the innovations that may ultimately emerge via basic neuroscience research will result in the development of medications and treatments that are far more effective than those available today.

[National Institute of Mental Health]

CAN A SIMPLE BLOOD TEST DIAGNOSE ALZHEIMER'S DISEASE?

A novel technique that may ultimately enable the accurate diagnosis of mild and moderate Alzheimer’s disease is being developed by a team of researchers led by Pedro Carmona of Madrid’s Instituto de Estructura de la Materia.  This technique utilizes a simple blood test, and appears to represent a less invasive approach than is currently available:  

At present, the most reliable and sensitive diagnostic techniques are invasive, e.g. require analysis of cerebrospinal fluid (the liquid that surrounds the brain and spinal cord). However, white blood cells (or mononuclear leukocytes) are also thought to carry amyloid-ß peptide in Alzheimer patients.

Using two-dimensional infrared spectroscopy, the technique proposed by Carmona and colleagues measures the amount of infrared radiation that is emitted or absorbed by an individual’s white blood cells.  Differing levels of radiation appear to be indicative of different stages of formation of amyloid-ß within the cells, which in turn appear to be indicative of different stages of Alzheimer's disease.

Researchers are optimistic that this new technique will provide a sensitive, low-cost, and rapid method by which the presence of Alzheimer’s disease can be identified, even at an early stage. 

[Medical News Today]

RESEARCHERS CREATE IN VITRO ALZHEIMER'S MODEL

A team of researchers led by Lawrence Goldstein of the University of California, San Diego School of Medicine has announced that they have successfully grown human Alzheimer's neurons in vitro.  Primary fibroblasts were taken from skin cells obtained from patients having familial (inherited) or sporadic Alzheimer's disease; these were then reprogrammed into induced pluripotent stem cells, which were in turn differentiated into functional neurons.  The researchers report that while the neurons exhibit normal activity, they also possess higher-than-normal levels of certain proteins that are indicative of Alzheimer's disease.

This appears to be a significant advance in the study of Alzheimer's disease, and one that researchers hope will lead to a deeper understanding of Alzheimer's pathogenesis.

With the in vitro Alzheimer's neurons, scientists can more deeply investigate how AD begins and chart the biochemical processes that eventually destroy brain cells associated with elemental cognitive functions like memory.

[Medical Xpress]

PROGRESS TOWARD UNDERSTANDING THE COMPLEX CIRCUITRY OF THE HUMAN BRAIN

An article published in yesterday’s Wall Street Journal provides an excellent, and optimistic, overview of progress being made to better understand the circuitry of the human brain.  This is clearly a huge undertaking, given that the brain contains approximately 100 billion neurons, with approximately 10,000 synapses branching from each one of these. 

One major effort is being undertaken by the Human Connectome Project.  Funded by the NIH, researchers at a number of institutions will utilize several different imaging techniques – including a novel technique known as ‘diffusion magnetic-resonance imaging’ – to map the brain’s largest conduits.  The brains of 1,200 healthy young adults, including 300 pairs of twins, will be scanned.  The resulting information will be analyzed on the Project’s supercomputer, together with each individual’s demographic information and medical records, with the goal of gaining significant insight into the brain’s neural connections.  Ultimately, it is hoped that this information will lead to a better understanding of how an individual's brain circuitry shapes healthy brain behavior, or instead results in brain disorders. 

"In essence, we will match form and function," said project principal investigator David Van Essen at Washington University in St. Louis.

Other notable efforts include those of Sebastian Seung at MIT, who is working to automate the mapping of individual synapses, and the Allen Institute for Brain Science, where researchers recently released a three-dimensional map illustrating the neural connections within the mouse brain, and are in the process of developing an interactive ‘human brain atlas’.  Allen Institute researchers are optimistic that these efforts, together with data obtained via the Human Connectome Project, will ultimately lead to greater insight into how the brain’s circuitry and underlying genes are related. 

One particularly optimistic development noted in the Journal’s article pertains to the more open sharing of information among brain researchers.  Pooled information is already being used by Michael Milham at the Child Mind Institute in New York to better understand the physical circuitry of the brain.  According to Milham: 

"People are seeing more of the merits of sharing … but there is still a lot of pushback." 

Going forward, it is hoped that the sharing of data will increase, and that this, together with novel imaging and automated data analysis techniques, will result not only in a greater understanding of how the normal brain is structured, but will also provide valuable insight into various disorders of the brain.

[Wall Street Journal]

DEVELOPING AN ALZHEIMER'S DRUG BY 2025: REALISTIC GOAL, OR OVERLY OPTIMISTIC?

Earlier this week, the advisory panel that is charged with providing specific recommendations to the federal government regarding the anticipated National Alzheimer’s Plan announced the goal of developing a treatment against Alzheimer’s disease by 2025. 

The development of an effective treatment would certainly address a significant unmet need, as there currently is no agent that is capable of preventing or curing this disease.  Apparently at least some members of the panel wished to set an even more aggressive target date.  In an interview this week with Nature, Ronald Peterson, who chairs the advisory panel, stated: 

“We’re leaning towards a 2020 goal as opposed to, say, 2025. The shorter time frame adds a sense of urgency.”  [Nature]

While Dr. Peterson concedes that it is unrealistic to expect that there will be a cure by 2020, he believes that it is feasible to expect significant progress by that date – assuming that federal funding for Alzheimer’s research increases significantly over the current level of less than $500 million per year.  However, the National Alzheimer’s Project Act does not provide for any additional funding, and the advisory panel only has the ability to recommend, not to mandate, that the government should provide additional financial support.  

Not everyone is convinced that targeting the development of an effective treatment by a particular year is beneficial.  An article published today by Reuters indicates: 

"No one set a deadline for the 'War on cancer' or in the fight against HIV/AIDS. We make progress and we keep fighting. The same should be true for Alzheimer's," said Dr. Sam Gandy, an Alzheimer's researcher at Mount Sinai School of Medicine.   "In my mind, that provides the unfortunate sense that we will have 'failed' if we don't have a cure by 2025."  [Reuters]

While researchers have devoted considerable time and effort toward finding a cure for Alzheimer’s, the disease is still not completely understood, and – given the significant delay between disease onset and the appearance of symptoms – it is likely that clinical trials for a novel Alzheimer’s therapeutic could take at least fifteen years.  This tends to suggest that it may be unrealistic to anticipate that an effective treatment will be available only 13 years from now, particularly since many promising new findings are still in preclinical stages.

The need for an agent that would prevent, delay, or cure Alzheimer's is clearly great, and will only increase going forward as the population continues to age.  We will therefore hope that researchers, and the pharmaceutical industry, will press on toward developing an effective treatment as quickly as possible – regardless of what specific date that may ultimately prove to be.