News

RESEARCHERS DISCOVER NEW FAMILY OF GENES INVOLVED IN MITOCHONDRIAL REGULATION

2012-05-22T14:09:01Z

A new family of proteins that localize to the mitochondria, and the genes encoding these, has been discovered by a team of researchers led by Eduardo Soriano of the Institute for Research in Biomedicine, Barcelona. Proteins encoded by these 'Armcx' genes, which are highly expressed in the nervous system, appear to be involved in regulating the movement and position of mitochondria within neurons:

“We have identified a set of new genes that are highly expressed in the nervous system and have a specific function in a biological process that is crucial for the activity and viability of the nervous system. These genes would be like an extra control in cellular mitochondrial trafficking and they interact with the major proteins associated with the regulation of mitochondrial transport”, explains Soriano.

Given that mutations in genes regulating mitochondrial transport are implicated in the development of various neurodegenerative diseases such as Parkinson's, it is certainly possible that alterations in the Armcx genes may be involved in disease pathogenesis. Interestingly, the researchers also found that proteins expressed by the Armcx genes localize to the cell nucleus in addition to the mitochondria, though their function within the nucleus is not yet known.

[IRB Barcelona]

MAY IS ALS AWARENESS MONTH

2012-05-18T20:23:27Z

This month marks the 21^st annual ALS Awareness Month in the U.S. Numerous efforts aimed toward building awareness of the disease, which impacts an estimated 30,000 people within the U.S. at any given time, are being spearheaded by both the ALS Association and the Muscular Dystrophy Association.

The ALS Association has posted a calendar on its website (http://www.alsa.org) which lists a different way to fight ALS for each day of the month; these “31 Ways in 31 Days” include signing up to volunteer, making a donation, attending an event, or becoming an advocate. In addition, the site provides links to stories about individuals and families throughout the U.S. who are coping with ALS, and instructions for enrolling in the National ALS registry.

The Muscular Dystrophy Association is also posting stories about individuals suffering from ALS on its site (http://awareness.als.mda.org). Called “ALS: Anyone’s Life Story”, these provide a glimpse into how these individuals and their families are coping with the disease. Visitors to the site are encouraged to share their own stories via “ALS: It’s My Story Too”. In addition to providing considerable financial support for ALS research, the Association provides support to patients in a variety of ways, including diverse programs such as “ALS Art” and “Easy Eats” – the latter providing recipes for easy-to-swallow foods and beverages.

We continue to hope that there soon will be a cure for ALS. In the meantime, it is heartening to see that there is support for those individuals and their loved ones who are so severely impacted by this devastating disease

ALZHEIMER'S RISK GENE APOE4 TRIGGERS INFLAMMATORY PATHWAY THAT WEAKENS BLOOD-BRAIN BARRIER

2012-05-18T16:00:40Z

It has previously been known that a specific variant of the ApoE gene, known as ‘ApoE4’, is a risk factor for the development of late-onset Alzheimer’s disease. Until now, the mechanism by which ApoE4 increases the risk of Alzheimer’s has remained unknown.

Using mice that were genetically engineered to express specific variants of the ApoE gene, a team of researchers led by Berislav Zlokovic of the University of Southern California has learned that ApoE4 appears to trigger an inflammatory cascade that weakens the blood-brain barrier. This damage to the blood-brain barrier enables neurotoxic proteins to infiltrate the brain from the bloodstream, causing damage to brain tissues and ultimately impacting brain function. While the two other variants of ApoE – that is, ApoE2 and ApoE3 – help to control the level of an inflammatory molecule known as cyclophilin A (CypA), the researchers observed that ApoE4 significantly raises levels of this molecule. These increased levels of CypA in turn activate a proinflammatory pathway that ultimately leads to the breakdown of the blood-brain barrier.

"The study demonstrates that damage to the brain's vascular system may play a key role in Alzheimer's disease, and highlights growing recognition of potential links between stroke and Alzheimer's-type dementia," said Roderick Corriveau, Ph.D., a program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS), which helped fund the research. "It also suggests that we might be able to decrease the risk of Alzheimer's disease among ApoE4 carriers by improving their vascular health."

In addition, the researchers believe that CypA may represent a potential target for the development of therapeutic agents.

[NIH News]

SNCA VARIANTS ASSOCIATED WITH FASTER DECLINE OF MOTOR FUNCTION IN PARKINSON'S PATIENTS

2012-05-16T15:40:31Z

A team of researchers led by Beate Ritz of UCLA has found that two specific variants of the SNCA gene appear to be associated with the more rapid decline of motor function in individuals suffering from Parkinson’s disease. The study tracked 233 patients over an average 5.1 years, and involved genetic analysis in addition to the assessment of motor abilities. The rate of progression of motor function was determined for each patient via assessing annual rates of change in Unified Parkinson’s Disease Rating Scale (UPDRS) exam motor scores. Each patient's SNCA variants were identified using standard genotyping methods. As reported in the journal PloS One, researchers found that individuals possessing the SNCA REP1 263bp promoter variant exhibited a significantly higher rate of progression of motor function decline. Progression rates were even higher in those patients possessing both the REP1 263bp promoter variant and the G-allele for rs356165.

It is hoped that these findings will enable clinicians to identify those patients who are at higher risk for the more rapid decline of motor abilities and who therefore may benefit more from early intervention. Study results may also have implications for the development of novel therapeutic agents for use against Parkinson's. It is anticipated that these two variants may represent potential targets for the development of novel therapeutic agents for use against Parkinson’s disease. Also, as stated by study co-author Shannon Rhodes:

“Because of these differences in the rate of disease progression, researchers can test potential therapies in individuals carrying the genetic variations, obtaining faster results on the efficacy of those drugs."

[Medical News Today]

VOLUME OF STRIATUM AND WHITE MATTER IN BRAIN MAY PREDICT HUNTINGTON'S DISEASE ONSET

2012-05-02T20:26:58Z

The ‘PREDICT-HD’ study was originally launched in 2001 in an effort to gain a greater understanding of the early stages of Huntington’s disease, particularly prior to diagnosis. The study follows healthy, pre-symptomatic individuals who are known to possess the genetic mutation characteristic of Huntington’s disease, and tracks the development and progression of behavioral and neurological changes leading up to diagnosis.

In conjunction with the PREDICT-HD study, a team of researchers led by Elizabeth Aylward of the Center for Integrative Brain Research, Seattle Children’s Research Institute, have demonstrated that neuroimaging may be of use in predicting disease onset. Specifically, Aylward and colleagues found that the volume of the striatum and white matter of the brain, as measured via magnetic resonance imaging, was significantly smaller in individuals who were within one to four years of diagnosis, in comparison with individuals who were not diagnosed with Huntington’s disease during that timeframe. These findings may have implications in the planning of future clinical trials, particularly in those that may involve individuals who carry the genetic mutation but are asymptomatic:

"We believe this group of individuals is well suited for drug intervention studies, as their brain involvement is not as severe as those who have already been diagnosed," said Dr. Aylward.

Individuals diagnosed with Huntington’s disease generally live only 15-20 years following disease onset. While there are certain drugs that may alleviate certain symptoms, there currently is no cure.

[EurekAlert!]

NEW REPORT - "DEMENTIA: A PUBLIC HEALTH PRIORITY"

2012-04-18T19:14:26Z

According to a report entitled "Dementia: A Public Health Priority", released last week by the World Health Organization and Alzheimer's Disease International, there were approximately 35.6 million individuals worldwide who were living with dementia in 2010. It is projected that the number of cases will nearly double every twenty years as the population continues to age, reaching 65.7 million individuals by 2030 and 115.4 million by 2050. Almost 7.7 million new cases are reported each year, which translates to one new case every four seconds.

The financial costs of dementia are high as well, totaling an estimated $604 billion in U.S. dollars in 2010; 89% of these costs were incurred in high-income countries. It is anticipated that costs will increase even more quickly than disease prevalence. Within the U.S. and other high-income countries, approximately 40% of financial costs correspond to "formal social care"; direct medical costs represent 15%; and "informal care" provided by family members, 45%. In low- and middle-income countries, informal care represents the predominant cost at present; institutionalization is uncommon, and community services are not generally available. Going forward, projected demographic changes indicate that fewer extended family members will be available to provide such care in low- and middle-income countries. This represents a particular challenge as the prevalence of dementia is projected to rise sharply in these countries, and indicates the need to ensure the availability of formal care alternatives.

The report provides compelling evidence that dementia is indeed a critical "global public health challenge", and that appropriate action must be taken:

Countries must include dementia on their public health agendas. Sustained action and coordination is required across multiple levels and with all stakeholders - at international, national, regional and local levels.

[World Health Organization]

FDA APPROVES NOVEL DIAGNOSTIC AGENT FOR IMAGING OF BETA-AMYLOID PLAQUES

2012-04-10T15:29:02Z

The U.S. Food and Drug Administration has announced its approval of Eli Lilly’s Amyvid ('Florbetapir F 18 Injection'), in conjunction with PET scans, for detecting beta-amyloid plaques within the brain. Amyvid is a radioactive dye that binds to beta-amyloid protein clumps, which characteristically accumulate within the brains of individuals suffering from Alzheimer’s disease. As beta-amyloid plaques may also be present within the brains of other individuals, Amyvid should not be viewed as a definitive diagnostic for Alzheimer’s. However, the absence of such plaques within the brain of an individual suspected of having Alzheimer’s – as could be detected via the use of Amyvid – would indicate that there is a different reason for the individual’s symptoms.

Eli Lilly will market Amyvid through its Avid Radiopharmaceuticals unit. As indicated by Avid CEO Daniel Skovronsky,

"The approval of Amyvid offers physicians a tool that, in conjunction with other diagnostic evaluations, can provide information to help physicians evaluate their patients.”

Worldwide, there are currently over 35 million individuals suffering from Alzheimer’s. It is anticipated that the market for diagnostic imaging agents for Alzheimer’s disease could be as high as $5 billion.

[Reuters]

THINGS LOOKING UP FOR U.S. BIOTECH VENTURE FUNDING

2012-04-04T20:34:26Z

According to an April 2, 2012 report by the financial services firm Burrill & Company, more than $2.6 billion in anticipated life sciences funding has been announced since the end of February of this year. Much of this funding focuses on supporting early-stage and translational research, with several initiatives aimed toward building life sciences hubs in various locations around the globe, including Russia, Wales, Quebec, and Europe. Within the U.S., one notable initiative will devote an anticipated $250 million toward providing support for translational research conducted at Cleveland’s University Hospital, including the development of certain compounds to proof-of-concept. Funding for these various initiatives is coming from various sources, including governments, big pharma, charitable organizations, and venture groups.

"These efforts reflect broad attempts to forge creative new models for funding translational research and spur development of important new therapies," says Burrill. "It also demonstrates that governments across the globe, despite facing fiscal pressure, see the importance of investing in the life sciences to build innovation-based economies that can provide high quality jobs."

While these initiatives appear to hold promise, Burrill notes that total global financings for the life sciences totaled only $12.5 billion during the first quarter of 2012, down from $29.2 billion one year ago. [FierceBiotech]

However, both Burrill & Company and the daily online biotech news service BioWorld Today report a more favorable scenario for venture capital financings within the U.S. According to BioWorld, first quarter 2012 biotech venture rounds rose during first quarter totaled $391 million in the U.S., representing a 34% increase over the first quarter of last year. Of this, Series A and seed deals brought in $98 million, with $136.5 million in funding for Series B deals and $156.6 million for higher rounds. Additionally, there were four IPOs during first quarter 2012, which together raised a total of $264.8 million – as compared with two IPOs that raised a total of $126.5 million during first quarter 2011. [BioWorld Today]

Burrill & Company also reports that life sciences stocks posted gains of 20.7 percent during first quarter 2012, as compared with the Dow Jones Industrial Average's 8.1 percent and the Nasdaq Composite Index's 18.7 percent gains. M&A activity has been somewhat sluggish, but is projected to increase during the second quarter of this year.

CHRONIC STRESS TRIGGERS PRODUCTION OF TAU PROTEIN AGGREGATES

2012-04-03T16:25:40Z

A team of researchers, led by Robert A. Rissman of the University of California, San Diego School of Medicine, has learned that chronic, repeated stress leads to the formation of insoluble tau protein aggregates within the brain cells of mice, particularly within the hippocampus. These aggregates are similar to the neurofibrillary tangles that are characteristic of Alzheimer’s disease, supporting the hypothesis that there is a link between chronic stress and Alzheimer’s.

It does not appear that single, acute episodes of stress trigger the production of these aggregates; rather, such episodes may actually promote brain plasticity and the ability to learn. Instead, the researchers believe that chronic stress appears to result in pathological changes within the neuronal circuitry of the brain, and that these changes – perhaps together with the affects that aging may have on an individual’s neurons - may contribute to the development of Alzheimer’s disease.

It is hoped that these findings could contribute to the identification of agents that could mitigate the damaging effects of chronic stress. As noted by Rissman:

“The idea is to use an antagonist molecule to reduce the effects of stress upon neurons. The stress system can still respond, but the response in the brain and hippocampus would be toned down so that it doesn’t result in harmful, permanent damage.”

[News Center, UCSD]

ANTIOXIDANTS MAY BE INCAPABLE OF PREVENTING ALZHEIMER'S DECLINE

2012-03-20T18:04:57Z

There currently are no drugs that are capable of preventing the onset, or halting the progression, of Alzheimer’s disease. While efforts to develop such drugs continue, numerous lifestyle/behavioral choices have been proposed as being at least somewhat effective in postponing – or even preventing – the development of this disease. For example, keeping mentally and physically active is thought to be of value, as is getting adequate sleep. Taking certain vitamins and dietary supplements, eating various foods such as non-fried fish, and even drinking a moderate amount of alcohol have also been proposed.

A recent study, led by Douglas Galasko of the University of California, San Diego, provides evidence that one of these approaches unfortunately does not appear to be effective. Specifically, Galasko and colleagues found that taking antioxidants - specifically, vitamins C and E, alpha-lipoic acid, and coenzyme Q - does not strengthen cognitive and behavioral abilities in individuals who have already been diagnosed with Alzheimer’s; instead, these antioxidants may even speed decline.

At the onset of the study, and following sixteen weeks of regulated antioxidant intake, researchers assessed each participant’s thinking, memory, and ability to perform daily functions. In addition, the levels of various Alzheimer’s biomarkers – amyloid beta 42, tau, and p-tau181 proteins, and F2-isoprostane – present in the cerebrospinal fluid of each study participant were measured. Galasko and colleagues found that cognitive and behavioral abilities did not change over the course of the study in the majority of participants, nor did the levels of the various biomarkers. One subgroup of participants did exhibit a decrease in the level of F2-isoprostane, which is indicative of oxidative stress, but this group also exhibited a greater decline in cognitive abilities and daily functioning – raising the specter that taking antioxidants could potentially contribute to a more rapid rate of decline. Clearly, more research remains to be done in order to more fully understand this potential link – but at the very least, these findings indicate that these antioxidants do not appear to be capable of slowing the progression of Alzheimer’s.

"We think that at the very least, these drugs... would not be likely to make a substantial contribution to the treatment of established Alzheimer's disease," Galasko told Reuters Health. "A question is whether there are more potent antioxidants that would be worth trying," he said - though it's unclear what those would be.

[Reuters]