Newly published research has brought to light new information on the molecular mechanisms that cause Huntington’s disease, and defines new pathways to therapy discovery. The results of the study are published in The Journal of Clinical Investigation.

Huntington’s disease is caused by the excessive repetition of a nucleotide triplet (CAG) in the Huntingtin gene. The number of CAG repetitions varies from person to person. Healthy individuals can have up to 36 repetitions. Nevertheless, as of 36 repetitions, Huntington’s disease develops. The direct consequence of this excess of repetitions is the synthesis of a mutated protein–different from what would be obtained without the additional CAG repetitions–which has been considered the main cause of the disease for the past 20 years.

“What we have observed in our study is that the mutated fragment acting as a conveyor–the so-called messenger RNA–is key in the pathogenesis,” says Dr. Eulàlia Martí, one of the lead authors of the paper.  “The research on this disease being done by most groups around the world seeking new therapeutic strategies focuses on trying to prevent expression of the mutated protein. Our work suggests that blocking the activity of messenger RNA (the ‘conveyor’), would be enough to revert the alterations associated with Huntington’s disease. We hope this will contribute to improving the strategies in place to find a cure.”

Paper: “Targeting CAG repeat RNAs reduces Huntington’s disease phenotype independently of huntingtin levels”
Reprinted from materials provided by the Centre for Genomic Regulation.

Researchers have developed a chemical compound called Fluselenamyl that detects amyloid clumps better than current FDA-approved compounds.

The compound, described in a paper published in Scientific Reports, potentially could be used in brain scans to identify the signs of early-stage Alzheimer’s disease or to monitor response to treatment.

Using human amyloid beta proteins, the researchers showed that Fluselenamyl bound to such proteins two to 10 times better than each of the three FDA-approved imaging agents for detecting amyloid beta. In other words, Fluselenamyl detected much smaller clumps of the protein, indicating that it may be able to detect the brain changes associated with Alzheimer’s disease earlier.

The next step is to move to testing in patients. The researchers have submitted an application to the National Institutes of Health (NIH) for a phase 0 trial, to establish whether Fluselenamyl is safe for use in humans and behaves in the human body the same way it behaves in mice. Phase 0 trials involve a low dose given to a small number of people to learn how a molecule is processed in the body and how it affects the body.

Paper: “Fluselenamyl: A Novel Benzoselenazole Derivative for PET Detection of Amyloid Plaques (Aβ) in Alzheimer’s Disease”
Reprinted from materials provided by Washington University in Saint Louis.

A meta-analysis has found that brain training – or Computerised Cognitive Training (CCT) – can improve memory in people with mild cognitive impairment, suggesting it may prevent dementia, which can take hold within a year.

Researchers have found that engaging in computer-based brain training can improve memory and mood in older adults with mild cognitive impairment – but training is no longer effective once a dementia diagnosis has been made.

The team reviewed more than 20 years of research and showed that brain training could lead to improvements in global cognition, memory, learning and attention, as well as psychosocial functioning (mood and self-perceived quality of life) in people with mild cognitive impairment.

Conversely, when data from 12 studies of brain training in people with dementia was combined, results were not positive.

Brain training is a treatment for enhancing memory and thinking skills by practising mentally challenging computer-based exercises – which are designed to look and feel like video games.

The team combined outcomes from 17 randomised clinical trials including nearly 700 participants, using a mathematical approach called meta-analysis, widely recognised as the highest level of medical evidence.

The results were published in the American Journal of Psychiatry.

Paper: “Computerized Cognitive Training in Older Adults With Mild Cognitive Impairment or Dementia: A Systematic Review and Meta-Analysis”
Reprinted from materials provided by the University of Sydney.

A combination of virtual reality and treadmill training may prove effective in preventing dangerous falls associated with aging, Parkinson’s disease, mild cognitive impairment or dementia, according to a new study published in The Lancet.

According to the study’s authors, the intervention combines the physical and cognitive aspects of walking, and could be implemented in gyms, rehabilitation centers and nursing homes to improve walking skills and prevent the falls of older adults and those with movement disorders like Parkinson’s disease.

The research team, in collaboration with partners across Europe, collected data at five clinical sites in Belgium, Israel, Italy, the Netherlands and the UK between 2013 and 2015. The participants, all aged 60-90, were able to walk at least five minutes unassisted, were on stable medications and, critically, had reported at least two falls in the six months prior to the start of the study. Nearly half of all participants had Parkinson’s disease, and some had mild cognitive impairment.

Participants were assigned to treadmill training with virtual reality or treadmill training alone. The virtual reality component consisted of a camera that captured the movement of participants‘ feet and projected it onto a screen in front of the treadmill, so that participants could „see“ their feet walking on the screen in real time.

The game-like simulation was designed to reduce the risk of falls in older adults by including real life challenges such as avoiding and stepping over obstacles like puddles or hurdles, and navigating pathways. It also provided motivation to the participants, giving them feedback on their performance and scores on the game.

While the incident rate of falls was similar in the two groups prior to the intervention, six months after training the rate of falls among those who trained with VR dropped by almost 50%. In contrast, there was no significant reduction in the fall rates among subjects who did not train with the VR.

Paper: “Addition of a non-immersive virtual reality component to treadmill training to reduce fall risk in older adults (V-TIME): a randomised controlled trial”

Reprinted from materials provided by Tel Aviv University.

Researchers have found a potentially promising treatment for Alzheimer’s disease, by noticing a similarity in the way insulin signaling works in the brain and in the pancreas of diabetic patients.

„In the pancreas, the Kir6.2 channel blockade increases the insulin signaling, and insulin signaling decreases the blood glucose levels,“ says Dr. Shigeki Moriguchi, one of the authors of the paper. „In the brain, insulin signaling increases the acquisition of memory through CaM kinase II activation by Kir6.2 channel blockade.“

The research group concluded that Alzheimer’s disease can be described as a ‘diabetic disorder’ of the brain.

Memantine, a drug widely used to treat Alzheimer’s disease, is a well-known inhibitor of the N-methyl-D-aspartate (NMDA) receptors that prevent excessive glutamate transmission in the brain. Researchers have now found that memantine also inhibits the ATP-sensitive potassium channel (Kir6.2 channel), improving insulin signal dysfunction in the brain.

In their experiment with mice, the researchers found that memantine treatment improved impaired hippocampal long-term potentiation (LTP) and memory-related behaviors in the mice through the inhibition of KATP channel Kir6.2.

The researchers say they hope the results of their study and the parallels drawn with diabetes will lead to new treatments for Alzheimer’s disease using the inhibition of Kir6.2 channel.

Paper: “Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer’s disease therapy”
Reprinted from materials provided by Tohoku University.

New research reveals that foods like fruits and vegetables that are high in antioxidant nutrients and carotenoids are associated with better function in amyotrophic lateral sclerosis (ALS) patients around the time of diagnosis. This is among the first studies to evaluate diet in association with ALS function and the first to show that healthy nutrients and antioxidants are associated with better ALS functioning. The findings are published in JAMA Neurology.

Researchers examined the links between nutritional intake and severity of ALS for patients who had ALS symptoms for 18 months or less. The study, which relied on nutrient intake reported using a food questionnaire, followed 302 participants recruited at 16 clinical centers throughout the U.S. The researchers used a validated measure of ALS severity and respiratory function.

The researchers found that “nutrition plays a role both in triggering the disease and why it progresses.” They also found that milk and lunch meats were associated with lower measures of function, or more severe disease. Two different statistical analyses both indicate that diet may help minimize the severity of ALS and point to the role of oxidative stress in ALS severity.
Paper: “Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis”
Reprinted from materials provided by: Columbia University