THE QUEST for ALZHEIMER APPLICABLE IN THE FUTURE

Alzheimer’s and other forms of dementia remain devastating conditions to both patients and their families, yet Lovestone says he feels more optimistic today than ever before. 

Scientists have known for years that the brains of Alzheimer’s patients are filled with a protein called beta amyloid that accumulates in between neurons, which are the cells that send and receive signals from your brain.  Yet drugs that target the formation of beta amyloid have so far been unsuccessful at stopping or reversing the disease.

                     Beta amyloid protein plaques in the brain of an Alzheimer's patient


 Recently, though, Janssen has focused on a different approach aimed at tau, a protein that accumulates in thread-like “tangles” inside of neurons. 

“These tangles can spread from one neuron to the next, killing brain cells,” Lovestone explains. “The compound developed by Janssen is designed to potentially prevent the spread of tau.”  

 Janssen also recently began an early clinical trial of an anti-tau vaccine, which could be given to patients even in extremely early stages of the disease, before symptoms have begun.

“The progress that we’ve made in the past few years has been enormous,” he says. “We have a much better understanding about how Alzheimer’s develops, which genes and other risk factors are driving the disease, and how it progresses. While there is still much to do, we are preparing for a future in which Alzheimer’s is a treatable—and even preventable—disease.”

Information on this page is provided for interest only on a "best efforts" basis and does not 
constitute personal advice. Always discuss medical conditions and related matters with your doctor.

Ref: https://www.jnj.com/innovation/

BREAKTHROUGH RESEARCH on ALZHEIMER

ALZHEIMER

For the first time, how the most well-known genetic risk factor for Alzheimer's disease causes signs in human brain cells and also, the scientists who managed to correct the gene and erase its harmful effects.

 

The apolipoprotein (APOE) gene in the development of Alzheimer's and its complex role has been studied extensively. For instance, researchers know that having one copy of the APOE4 gene variant raises the risk of Alzheimer's by two to three times. And, having two copies of this genetic variant puts people at a 12-fold higher risk. Normally, APOE's role is to provide instructions for creating the protein of the same name. In combination with fats, APOE creates lipoproteins, which help to transport and regulate levels of cholesterol throughout our bloodstream.

However, the E4 version of the gene seems to be particularly damaging to the brain, with several studies showing that this genetic variant increases the risk of toxic amyloid beta and tau buildup. But why is that? What makes the E4 variant of this gene so much more harmful than other variants? Researchers at the Gladstone Institutes in San Francisco, CA, wanted to find out. Their findings have just been published in the journal Nature Medicine.

More specifically, the researchers wanted to locate and understand the fine yet crucial difference between the E3 and E4 variants that makes the APOE4 gene so devastating.
Is it a case, the researchers wondered, of the E4 variant making APOE3 lose some of its functions? Or is it the case that more APOE4 has toxic effects?

Lead investigator Dr. Yadong Huang — a professor of neurology and pathology at the University of California, San Francisco — explains the importance of this question.
"It's fundamentally important," he says, "to address this question because it changes how you treat the problem. If the damage is caused due to the loss of a protein's function, you would want to increase protein levels to supplement those functions." "But if the accumulation of a protein leads to a toxic function, you want to lower production of the protein to block its detrimental effect."

To find out, the researchers modeled the disease in human cells, examining the effect of APOE4 on human brain cells for the first time. Dr. Huang explains why changing the disease model was, in itself, a huge step for Alzheimer's research. "Many drugs," he explains, "work beautifully in a mouse model, but so far they've all failed in clinical trials. One concern within the field has been how poorly these mouse models really mimic human disease."

Applying stem cell technology to skin cells from people with Alzheimer's who had two copies of the APOE4 gene, Dr. Huang and his team created neurons. The researchers also created brain cells using skin cells from people who didn't have Alzheimer's and had two copies of the APOE3 gene. The scientists found that in human brain cells, the APOE4 protein has a "pathogenic conformation" — meaning that it has an abnormal form that prevents it from functioning properly, leading to a series of disease-causing problems. Namely, "APOE4-expressing neurons had higher levels of tau phosphorylation," the authors write, which was "unrelated to their increased production of amyloid-[beta] peptides, and [...] they displayed GABAergic neuron degeneration." Importantly, they also found that "APOE4 increased [amyloid-beta] production in human, but not in mouse, neurons." "There's an important species difference in the effect of APOE4 on amyloid beta," explains first study author Chengzhong Wang.

CORRECTING FAULTY GENE

Next, Dr. Huang and team wanted to see whether it was the loss of APOE3 or the accumulation of APOE4 that caused the disease. So, they compared neurons that did not produce either the E3 or the E4 variant of the protein with cells that had APOE4 added to them.

The former continued to behave normally, while adding APOE4 led to Alzheimer's-like pathologies. This confirmed the fact that it is the presence of the APOE4 that causes the disease.

As a final step, Dr. Huang and his team looked for ways in which to fix the faulty gene. To this end, they applied a previously developed APOE4 "structure corrector." The so-called structure corrector has been shown in previous research, led by the same Dr. Huang, to change the structure of APOE4 so that it looks and behaves more like the inoffensive APOE3.

Applying this compound to human APOE4 neurons corrected the defects, thereby eliminating signs of the disease, restoring normal cell function, and helping the cells to live longer.

The researchers conclude:

"Treatment of APOE4-expressing neurons with a small-molecule structure corrector ameliorated the detrimental effects, thus showing that correcting the pathogenic conformation of APOE4 is a viable therapeutic approach for APOE4-related [Alzheimer's disease]."

 

Information on this page is provided for interest only on a "best efforts" basis and does not 
constitute personal advice. Always discuss medical conditions and related matters with your doctor.

Reference:  https://www.medicalnewstoday.com/articles/321455.php

Robotic Vitroretinal Surgery

The *Preceyes system focuses on robotic assistance for vitreoretinal (VR) surgeons. The system is designed to provide assistance so that the surgeon can work with higher accuracy and precision, while at the same time improving on dexterity. The system is expected to improve treatment outcomes for patients and increase procedural safety, while the higher degree of automation inherent to robotics is also expected to improve clinical workflows and bring down costs.

The Preceyes robot is unique because of both its ultra-high-precision and ultra-high-dexterity. This is achieved by scaling down movements in the system, which dramatically increases precision by more than a factor of 10, while also filtering out any surgeon hand tremor. The instruments used in VR surgery are so fine that they often bend and deform when inserted into the eye by hand—the level of control in our system means this does not happen. The integration of the system with the conventional operating room is also very sophisticated, and the system can be used with the majority of operating tables.

Firstly there is patient access to surgery. The level of manual control and precision that these VR surgeons have is incredible, but it takes years and years of training to get to that level. Also, a VR surgeon can quickly reach an age where hand tremor and other inaccuracies can become a problem, often long before the normal retirement age. So being able to use robotics to take over some of the precision and dexterity allows us to train surgeons faster and extend the number of years they can work once trained. This is, of course, an even bigger issue in emerging economies, where there is currently a very significant shortage of VR surgeons. But, given that the incidence of VR diseases is expected to double in the next 15 years, there will also soon be a shortage of VR surgeons in developed economies as well.

The other benefit is the improved accuracy and precision of the surgery overall, which is expected to lead to dramatically improved patient safety and health outcomes. This is a pattern that is true for all robotic surgery. The ultra-high precision required in VR surgery would suggest that the gains for patients from robotic assistance could be even greater.

Finally, the technology opens up opportunities for totally new therapies, particularly gene and cell therapies, vein cannulation, and the possibility of sub-retinal implants. With the Preceyes system you can place a needle in the sub-retinal space with a 10 micrometer precision and keep it there for two or three minutes while you carefully inject a fluid—that is something that is just impossible manually.

*  Preceyes is currently undergoing first-in-human trials, which is a development stage.


Information on this page is provided for interest only on a "best efforts" basis and does not 
constitute personal advice. Always discuss medical conditions and related matters with your doctor.

Reference: http://www.medgadget.com

Prostrate Cancer Screening - A Better Way

Current Method

Current methods of prostate cancer screening, such as prostate-specific antigen (PSA) tests and digital rectal exams (DRE), are somewhat unreliable and can lead to many uncertainties for both patient and urologist. Prostate biopsy, the most reliable method of detection, is a challenge because of the difficulties in visualizing not only the entirety of the prostate, but also the location of the biopsy needle. Trans-rectal ultrasound-guided prostate biopsy (TRUS), the current biopsy standard, commonly suffers from poor image resolution, and the biopsy needle often passes through tumor-free areas of the prostate - potentially missing the tumor entirely.

In addition, it can be difficult to distinguish between lesions that necessitate only a “watchful waiting” period and more aggressive lesions that require therapy. A more confident characterization of the type of lesion could help avoid the risk of side effects such as incontinence, impotence and bowel problems that can result from therapy.

This is the current method of biospy and its drawbacks from random sampling:

To obtain prostate tissue for cancer testing, a series of needles is poke  (between 12 and 24) into different areas of the gland, guided by ultrasound. This method was used since the 1980s. The ultrasound images help to place the needles properly, but the pictures aren’t distinct enough to be able to tell if it is cancerous from normal prostate tissue, so there is no certainty of the target to home in on suspicious areas for biopsy. The truth is the current method is a scattershot “blind” approach in the hope that, if a tumor is present, one of the needles will encounter it. These random biopsies can miss some harmful tumors, while turning up others that are inconsequential and may end up being treated unnecessarily.

 

The new Technology - Image Guided Prostrate Biopsy

An MRI scan is better than ultrasound at revealing details in soft tissue in the case of the prostate gland. Prostate cancer cannot be diagnose from an MRI image, but can certainly it can be used to identify suspicious areas that warrant closer examination with a needle biopsy.  The new fusion guided targeted biopsy technology combined the detailed MRI scans with live real-time ultrasound images of the prostate will enable a better diagnosis and outcome.
 
Targeted MR/ultrasound biopsy is poised to become a new standard in prostate care. This technique fuses pre-biopsy MR images of the prostate with ultrasound-guided biopsy images in real time, for excellent delineaon of the prostate and suspicious lesions, as well as clear visualization of the biopsy needle.

The fusion of the MR and ultrasound images uses electromagnetic tracking, similar to your car’s GPS system. A small, localized electromagnetic field is generated and used in conjunction with a navigation sensor mounted to the trans-rectal ultrasound probe to determine the location and spatial orientation of the biopsy device. A sophisticated algorithm maintains the fusion of MR and ultrasound images even when the patient moves.

The Use of Uronav

 

A revolutionary new test can better pinpoint trouble spots and lead to a quicker prostate cancer diagnosis. Invivo’s UroNav uses a combination of MRI and Ultrasound. Unlike traditional biopsies that take twelve samples, UroNav allows doctors to identify and remove only what looks irregular. “Standard prostate biopsies are random and are systematically obtain random samplings from the prostate. There’s no guarantee that a biopsy will hit the cancer. For men who are moderate to high risk, UroNav can cut down on random biopsies that may find nothing. It can also help to diagnose the cancer faster. The new technology, called UroNav, is like taking the blindfold off. The new UroNav technology that is being used utilizes the UroNav Fusion Biopsy System, and fuses (overlay) pre-biopsy MR images of the prostate with ultrasound-guided biopsy images in real time, for clear delineation of the prostate and suspicious lesions, as well as clear visualization of the biopsy needle.

Prostate cancer specialists at the University of Michigan Comprehensive Cancer Center (link is external) are refining prostate cancer diagnosis to better identify those cancers that are more likely to grow quickly and spread to other parts of the body.
The University of Michigan is the first in the region to offer men a new technology that combines MRI and real-time ultrasound to help guide a biopsy needle, ensuring that tissue from all suspicious areas is captured.

The fusion guided biopsy approach isn’t perfect. A recent study found that the fusion method missed almost as many prostate tumors as did standard biopsy. But as my Cleveland Clinic colleague, urologist J. Stephen Jones, MD, noted, the cancers that the fusion method missed were far more likely to be clinically insignificant ones.

Put another way, fusion guided biopsy is better than the existing approach at finding prostate tumors we need to treat, while overlooking those we don’t need to worry about.

Each year in the United States, about 700,000 men with worrisome PSA levels undergo repeat prostate biopsies. The fusion guided biopsy approach should help reduce that number, by giving better information the first time around. This tool should also be a boon to men who’ve been diagnosed with small, slow-growing prostate tumors and who are on active surveillance – also called watchful waiting – by possibly reducing the number of biopsies they must undergo.

Information on this page is provided for interest only on a "best efforts" basis and does not 
constitute personal advice. Always discuss medical conditions and related matters with your doctor.

Refernce: http://www.uofmhealth.org & https://health.clevelandclinic.org

Alzheimer Disease

Like all types of dementia, Alzheimer's is caused by brain cell death. It is a progressive neurodegenerative disease, which means there is progressive brain cell death that happens over a course of time. The total brain size shrinks with Alzheimer's - the tissue has progressively fewer nerve cells and connections. A neurodegenerative type of dementia, the disease starts mild and gets progressively worse. 

While they cannot be seen or tested in the living brain affected by Alzheimer's disease, postmortem/autopsy will always show tiny inclusions in the nerve tissue, called plaques and tangles:
 

• Plaques are found between the dying cells in the brain - from the build-up of a protein called beta-amyloid (you may hear the term "amyloid plaques").
• The tangles are within the brain neurons - from a disintegration of another protein, called tau. 

The abnormal protein clumps, inclusions, in the brain tissue are always present with the disease, but there could be another underlying process that is actually causing the Alzheimer's - scientists are not yet sure.

This sort of change in brain nerves is also witnessed in other disorders, and researchers want to find out more than just that there are protein abnormalities - they also want to know how these develop so that a cure or prevention might be discovered.  

The most common presentation marking Alzheimer's dementia is where symptoms of memory loss are the most prominent, especially in the area of learning and recalling new information. But the initial presentation can also be one of mainly language problems, in which case the greatest symptom is struggling to find the right words.

If visuospatial deficits are most prominent, meanwhile, these would include inability to recognize objects and faces, to comprehend separate parts of a scene at once (simultanagnosia), and a type of difficulty with reading text (alexia). Finally, the most prominent deficits in "executive dysfunction" would be to do with reasoning, judgment and problem-solving.

Symptoms of Alzheimer's Disease

1. Worsened ability to take in and remember new information, for example:

• "Repetitive questions or conversations
• Misplacing personal belongings
• Forgetting events or appointments
• Getting lost on a familiar route."

2. Impairments to reasoning, complex tasking, exercising judgment:

• "Poor understanding of safety risks
• Inability to manage finances
• Poor decision-making ability
• Inability to plan complex or sequential activities."

3. Impaired visuospatial abilities (but not, for example, due to eye sight problems):

• "Inability to recognize faces or common objects or to find objects in direct view
• Inability to operate simple implements, or orient clothing to the body."

4. Impaired speaking, reading and writing:

• "Difficulty thinking of common words while speaking, hesitations
• Speech, spelling, and writing errors."

5. Changes in personality and behavior, for example:

• Out-of-character mood changes, including agitation; less interest, motivation or initiative; apathy; social withdrawal
• Loss of empathy
• Compulsive, obsessive or socially unacceptable behavior.

 

Stages of Alzheimer's Disease

 The progression of Alzheimer's can be broken down into three basic stages:

• Preclinical (no signs or symptoms yet)
• Mild cognitive impairment
• Dementia.

The Alzheimer's Association has broken this down further, describing seven stages along a continuum of cognitive decline based on symptom severity - from a state of no impairment, through mild and moderate decline, and eventually reaching "very severe decline." 

 It is not usually until stage four that a diagnosis is clear - here it is called mild or early-stage Alzheimer's disease, and "a careful medical interview should be able to detect clear-cut symptoms in several areas." 

Mild Alzheimer;s Disease (early stage)

In the early stages of Alzheimer's, a person may function independently. He or she may still drive, work and be part of social activities. Despite this, the person may feel as if he or she is having memory lapses, such as forgetting familiar words or the location of everyday objects.
Friends, family or neighbors begin to notice difficulties. During a detailed medical interview, doctors may be able to detect problems in memory or concentration. Common difficulties include:

• Problems coming up with the right word or name
• Trouble remembering names when introduced to new people
• Having greater difficulty performing tasks in social or work settings
• Forgetting material that one has just read
• Losing or misplacing a valuable object
• Increasing trouble with planning or organizing

Moderate Alzheimer's Disease (middle stage)

Moderate Alzheimer's is typically the longest stage and can last for many years. As the disease progresses, the person with Alzheimer's will require a greater level of care.
You may notice the person with Alzheimer's confusing words, getting frustrated or angry, or acting in unexpected ways, such as refusing to bathe. Damage to nerve cells in the brain can make it difficult to express thoughts and perform routine tasks.
At this point, symptoms will be noticeable to others and may include:

• Forgetfulness of events or about one's own personal history
• Feeling moody or withdrawn, especially in socially or mentally challenging situations
• Being unable to recall their own address or telephone number or the high school or college from which they graduated
• Confusion about where they are or what day it is
• The need for help choosing proper clothing for the season or the occasion
• Trouble controlling bladder and bowels in some individuals
• Changes in sleep patterns, such as sleeping during the day and becoming restless at night
• An increased risk of wandering and becoming lost
• Personality and behavioral changes, including suspiciousness and delusions or compulsive, repetitive behavior like hand-wringing or tissue shredding

Severe Alzheimer's Disease (late stage)

In the final stage of this disease, individuals lose the ability to respond to their environment, to carry on a conversation and, eventually, to control movement. They may still say words or phrases, but communicating pain becomes difficult. As memory and cognitive skills continue to worsen, personality changes may take place and individuals need extensive help with daily activities.
At this stage, individuals may:

• Require full-time, around-the-clock assistance with daily personal care
• Lose awareness of recent experiences as well as of their surroundings
• Require high levels of assistance with daily activities and personal care
• Experience changes in physical abilities, including the ability to walk, sit and, eventually, swallow
• Have increasing difficulty communicating
• Become vulnerable to infections, especially pneumonia

  

How common is Alzheimer's Disease?

In the US, the most recent census has enabled researchers to give estimates of how many people have Alzheimer's disease. In 2010, some 4.7 million people of 65 years of age and older were living with Alzheimer's disease in the US.

 
The 2013 statistical report from the Alzheimer's Association gives a proportion of the population affected - just over a tenth of people in the over-65 age group have the disease in the US. In the over-85s, the proportion goes up to about a third.
 
  

Information on this page is provided for interest only on a "best efforts" basis and does not 
constitute personal advice. Always discuss medical conditions and related matters with your doctor.

Reference: http://www.medicalnewstoday.com