Category Archives: Research News (General)

A drug that acts like a growth-promoting protein in the brain reduces degeneration and motor deficits associated with Huntington’s disease in two mouse models of the disorder.

Previous studies of people with Huntington’s disease point to a link between low levels of a neurotrophin called brain-derived neurotrophic factor (BDNF) and symptoms of the disorder.

In the current study, which appeared in the Journal of Neuroscience, Frank Longo, MD, PhD, and others at Stanford University, tested LM22A-4, a drug that specifically binds to and activates the BDNF receptor TrkB on nerve cells, in mice that model the disorder. They found LM22A-4 reduces abnormal protein accumulation, delays nerve cell degeneration, and improves motor skills in the animals.

The findings add to a growing body of evidence that protecting or boosting neurotrophins – the molecules that support the survival and function of nerve cells – may slow the progression of Huntington’s disease and other neurodegenerative disorders.

The U.S. Food and Drug Administration on October 25 approved a second amyloid imaging agent. Flutemetamol is an F18-labeled ligand developed by GE Healthcare. It joins florbetapir, developed by Avid Pharmaceuticals/Eli Lilly and Company.

Flutemetamol differs slightly from its cousin because it is approved to report the intensity of binding to amyloid plaques in false color. This could make scans easier to read, some experts agreed. The compound will be commercially available in early 2014.

In regulatory terms, both are approved to indicate whether amyloid is present, and thereby support or refute an AD diagnosis. Neither is intended to diagnose AD on its own or replace other routine clinical tests for cognitive decline. Neither compound is approved to quantify amyloid plaques in the brain. That is something both companies are exploring.

Both agents will be made available to both neurologists and researchers. GE Healthcare has submitted an application for approval to the European Medicines Agency (EMA), and will apply in various other countries in the coming months and years. Florbetapir has already gotten EMA approval, and Lilly/Avid is seeking approval in other areas of the world.

Source:  AlzForum website – 21 Nov 2013

Researchers studying the natural history of Alzheimer’s disease are grappling with a puzzling group of volunteers—amyloid-free and cognitively normal older adults who show other biomarker evidence of neurodegeneration.

Researchers studying the natural history of Alzheimer’s disease are grappling with a puzzling group of volunteers—amyloid-free and cognitively normal older adults who show other biomarker evidence of neurodegeneration.

Source: AlzForum website – 08 Nov 2013 </time><//time>

The largest international study ever conducted on Alzheimer’s disease, the I-GAP (International Genomics Alzheimer’s Project) consortium has identified eleven new regions of the genome involved in the onset of the disease.

This research gives an overview of the molecular mechanisms underlying the disease, opening up to a better understanding of the pathophysiology of this disease.

These results, detailed inNature Genetics, could not have been obtained without this unique worldwide collaborative effort.

In addition to the well-established association at the APOE locus, they identified 19 genomic regions significantly associated with late-onset Alzheimer’s disease, 11 of which are new susceptibility loci. Their findings reinforce pathways previously implicated in Alzheimer’s disease pathology, including immune response, inflammation, cell migration and lipid transport pathways. They also suggest new candidate genes and pathways that may be involved in disease risk.

These 11 new confirmed genes can open new avenues in the understanding of the occurrence of Alzheimer’s disease. Thus one of the most significant associations were found in the region HLA-DRB5/DRB1 major histocompatibility complex. This finding is interesting in several ways. First, it confirms the involvement of the immune system in disease. In addition, this same region is also found associated with two other neurodegenerative diseases, multiple sclerosis and Parkinson’s disease.

About I-GAP:http://www.alz.org/news_and_events_21649.asp

University of California Irvine’s trailblazing 90+ Study, aimed at learning more about the “oldest old, will continue for at least another five years, thanks to a $9.5 million renewal grant from the US National Institute on Aging.

The 90+ Study is among the largest studies of the oldest old in the world, with clinical, pathological and genetic research being conducted on more than 1,600 participants. Results obtained thus far have provided researchers across the globe with valuable information about aging."

The UC Irvine study is among the few to look at dementia in people over age 90. With the renewed round of funding over the next five years, 90+ researchers plan to employ PET and MRI scans to address these questions: Why do many of the oldest old have Alzheimer’s or vascular pathology in their brains but not show signs of dementia? Are they in the preclinical stages of disease? Will their cognitive abilities eventually decline?

The researchers also intend to monitor blood pressure and oxygen saturation over 24-hour spans to see if dips in blood pressure, particularly during the night, or periods of fluctuation are associated with cerebral microinfarctions or other diseases of the brain that can cause dementia.

A chemical substance has been identified which shows signs of being able to halt a range of neurodegenerative diseases in mice.

Researchers at the University of Leicester’s Medical Research Council Toxicology Unit, investigating prion disease in mice, have found a common feature across all types of brain cell death. Looking at the natural defence mechanisms of brain cells, they found that brain cells respond by shutting down protein production when attacked by a virus (in order to halt the virus’s spread).

A range of neurodegenerative diseases involve the formation of faulty or "misfolded" proteins, and these activate similar defence mechanisms. In Parkinson’s Disease it is alpha-synuclein which is the errant protein, in Alzheimer’s Disease it is amyloid and tau, and in the case of Huntingdon’s Disease it is another different protein.

The researchers believe the specific errant protein is irrelevant, because it is how cells deal with misfolded protein which is important. The presence of misfolded proteins causes brain cells to shut down protein production for a long period, eventually resulting in cell death.

The researchers believe they may be able to disrupt this process by the administration of a particular compound, thereby halting neurodegeneration; at least in mice with prion disease so far.

Research teams from Sheffield, UK and Milan, Italy looked at the factors which might explain the differences observed in speed and severity in the progression of motor neuron disease (MND).

Researchers used a scientific technique known as gene expression profiling to identify factors within motor neurones that control vulnerability or resistance to MND in order to shed light on the factors important for the speed of motor neurone injury in human patients.  The research, published in the scientific journal Brain, investigated two mouse models of MND caused by an alteration in the SOD1 gene, a known cause of MND in humans. One of the strains had a rapidly progressing disease course and the other a much slower change in the symptoms of MND.

The study, funded by the Motor Neurone Disease Association, revealed new evidence at the point of onset of the disease, before muscle weakness was observed, showing key differences in major molecular pathways and the way the protective systems of the body responded, between the profiles of the rapid progressing and slow progressing models. In the case of the model with rapidly progressing MND the motor neurones showed reduced functioning of the cellular systems for energy production, disposal of waste proteins and neuroprotection. Motor neurones from the model with more slowly progressing MND showed an increase in protective inflammation and immune responses and increased function of the mechanisms that protect motor neurones from damage.

Neurobiologists from the Friedrich Miescher Institute for Biomedical Research proved that excitability protects motor neurons from degeneration in amyotropic lateral sclerosis, a rare neurodegenerative disease.

By modulating excitability researchers could influence the rate of motor dysfunction and muscle denervation, and slow the progression rate of the disease.

This is important because it points to a possible way to delay the progression of this so far incurable disease.

Their results are published online in Neuron. 

Having depression may increase your risk of developing Parkinson’s disease by up to three times, according to a new study.

Depression is known to raise the risk of a host of diseases including cancer and stroke, but although it is known to be more common among Parkinson’s patients than the general population, it remains unclear whether it is a cause or a symptom.

Researchers from Taipei Veterans General Hospital in Taiwan examined the medical records of 4,634 people who suffered from clinically diagnosed depression, and 18,544 who did not, over a ten-year period.
They found that 66 people with depression, or 1.42 per cent, went on to be diagnosed with Parkinson’s during the next decade compared with 97 of those without depression, or 0.52 per cent.

After other factors such as age were taken into account, patients with depression were found to be 3.24 times more likely to be diagnosed with Parkinson’s than those without.

Even when researchers excluded the records of patients who were diagnosed with Parkinson’s shortly after their depression diagnosis, the link was still apparent suggesting that depression raises the risk of Parkinson’s over the long term.

In a joint announcement, three French Ministers expressed their support for people with dementia and their carers on World Alzheimer’s Day.

Marisol Touraine (Social Affairs and Health Minister), Geneviève Fioraso (Minister for Higher Education and Research) and Michèle Delaunay (Minister for the Elderly and Autonomy) also provided an update on the progress of the new “Neurodegenerative Plan”. This will be the continuation of France’s pioneering Plan Alzheimer.

Following the evaluation of the 3rd Plan Alzheimer (2008-2012) by Professors Joël Ankri and Christine Van Broeckhoven, four thematic working groups are being formed to identify the measures and actions of the new plan. The themes are:

• improve diagnosis and early detection of the disease
• respond to patients’ needs at each stage of the disease and in the entire country
• increase awareness and conform to the highest standards of ethics, quality and welfare
• increase the quantity and quality of research.

The new Neurodegenerative plan is expected to be finalised in the first quarter of 2014.