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Green Grace Pharmacy

Green Grace Pharmacy
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Diazepam tablets are used to treat a number of conditions, including: In adults- short term relief (2-4 weeks only) of severe anxiety, which is an emotional state where you may sweat, tremble, feel anxious and have a fast heart beat and may occur alone or with insomnia (trouble sleeping) or mental health problems , helping muscles relax and for muscle spasm and cerebral palsy (a condition affecting the brain which causes movement problems and rigidity or stiffness), epilepsy (when taken with other medicines), patients with the symptoms of alcohol withdrawal or helping to relax nervous dental patients


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Pain Management NYC (Bronx)

Pain Management NYC (Bronx)
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We are one of New York City is premier Pain Management & Pain Treatment Centers. Our pain doctors are among the best pain relief physicians in the USA, part of the Olympic Games medical team, and experts in the latest pain treatments for knee pain, neck pain, back pain, etc. Our knee pain doctors offer the newest pain relief treatment for back of knee pain. Are you looking for a back pain doctor near you? If you have upper or lower back pain, neck pain, or shoulder pain, our trusted pain specialists, board-certified physicians offer the latest non-invasive pain treatments. Visit our new pain control & sports injury clinic in the Bronx, NY to meet the best-rated pain management doctors who provide effective pain treatments and quality pain care.
In our sports injury clinic, we offer services such as:
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If you have any questions or concerns, our team of top pain management specialists in New York is here to help. Contact us: (718) 998–0504.
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Pain Management NYC
1976 Crotona Parkway, Suite 3A
Bronx, NY 10461
(718) 998–0504

Web Address: https://www.painmanagementnyc.com

Bronx, NY Office: https://www.painmanagementnyc.com/bronx-pain-management

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Nearby Locations:
Crotona | Claremont | Crotona Park East | Charlotte Gardens | Van Nest | Soundview
10459 | 10460 | 10462

Working Hours:
Monday: 8:00 AM — 6:00 PM
Tuesday: 8:00 AM — 6:00 PM
Wednesday: 8:00 AM — 6:00 PM
Thursday: 8:00 AM — 6:00 PM
Friday: 8:00 AM — 6:00 PM
Saturday, Sunday: Closed

Payment: cash, check, credit cards.

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Sanjiv Lakhanpal

Center for Vascular Medicine of Columbia
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Are you ready to unleash your body's full potential for optimal vascular health? Center for Vascular Medicine of Columbia is your trusted partner in this transformative journey. Our esteemed vascular surgeons in Columbia are wholly dedicated to diagnosing and treating a wide array of deep venous and arterial conditions affecting your pelvis and lower extremities, helping you break free from discomfort and embrace a life of enhanced vitality. Our mission is to combine innovative treatments with personalized care, ensuring that your experience at our state-of-the-art facility in Columbia, Maryland, exceeds your expectations. We understand that navigating vascular health concerns can be challenging, and that's why our team is committed to providing a welcoming and supportive environment throughout your treatment journey. 

 

Phone:301-486-4690


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joined 1 year, 7 months ago

Dr.Hinesh Acharya

General Physician | Consultant Physician in Ahmedabad

Dr. Hinesh Acharya MD Physician is the best Consultant Physician in Ahmedabad. He has been practicing medicine for many years and is a General Physician in Ahmedabad. Dr. Hinesh Acharya specializes in diagnosing and treating illnesses diseases like typhoid, food poisoning, and infectious diseases.


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joined 2 years, 8 months ago

Dr. Mukesh Sharda BAMS, Ph.D., is a renowned Ayurvedic rheumatologist-CEO and Founder of Dr. Sharda Ayurveda practicing for more than 15+ years and successfully treated more than 50k+ patients worldwide for all chronic diseases.


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  • The CoVID-19 pandemic has been controlled by government policies that restrict individual behaviour 
  • Even if the accelerated vaccine development goes to plan and is successful, government restrictions will be necessary for some time yet 
  • Recent research suggests that, at the height of the CoVID-19 pandemic, people with narcissistic and other “dark” personality traits flouted public health restrictions  
  • Research has also shown that the coronavirus can be spread by a relatively small group of individuals who break public health protocols 
  • Could a small group of asymptomatically infected individuals with narcissistic traits trigger a renewed and significantly more devastating outbreak of CoVID-19?
  
Narcissism and a second more devastating wave of CoVID-19
 
 
Research suggests that in early 2020, at the height of the CoVID-19 pandemic, people with narcissistic and other “dark” personality traits, (Machiavellianism and psychopathy) flouted public health restrictions, such as social distancing, stay-at-home measures, mask-wearing and hand washing, introduced to prevent the spread of the coronavirus.
 
The fastest and deepest global economic shock in history

The outbreak of CoVID-19 in December 2019 started an epidemic of acute respiratory syndrome in humans in Wuhan, China, which quickly became a pandemic responsible for the fastest and deepest global economic shock in history. In a matter of weeks, stock markets collapsed, credit markets froze, huge bankruptcies occurred, unemployment rose above 10% and annual GDP rates contracted by 8% or more. In the absence of either a vaccine or a therapy, the social and behavioural sciences were used by governments to help align human behaviour with the recommendations of epidemiologists and public health experts to reduce the impact of the coronavirus outbreak. 
 
Measures were successful and as nations regained control of the virus’s transmission and reduced the burden on their healthcare systems, restrictions were relaxed or removed to re-energise damaged economies and encourage more viable lifestyles with the virus still in circulation. In many countries, this increased the incidence levels of CoVID-19, hospitalisations and deaths; and governments had no alternative but to re-instate selected restrictions on people’s behaviours.
 
Now, some ten months after the initial outbreak, governments throughout the world are bracing themselves in the knowledge that a relatively small group of people who flout restrictions could cause the coronavirus to return, which some analysts suggest could be more devastating than the impact of its initial outbreak. This is because healthcare systems have been significantly weakened and are struggling to cope with huge backlogs of patients whose treatments have been delayed because of the coronavirus, economies have been damaged, and the annual winter flu epidemic is expected in most Western developed nations.
 
In this Commentary

This Commentary describes the findings of three recent studies, which examine the relationships between the Dark Triad traits (i.e., narcissism, Machiavellianism and psychopathy) and behaviours related to the COVID-19 pandemic. Findings suggest that, at the height of the pandemic in March and April 2020, people with narcissistic and psychopathic personality traits were more likely to ignore rules, such as hand washing, social distancing, staying-at-home and mask-wearing and therefore could have become super spreaders of the disease. The Commentary focusses on narcissistic traits. We begin by underlining some of the challenges of developing and manufacturing a CoVID-19 vaccine at scale, which is safe and effective. We then describe Narcissistic Personality Disorder (NPD) and the R number, which governments have used to explain how well the virus is being controlled. We also describe the lesser known K metric, which is critical to epidemiologists’ attempts at understanding how CoVID-19 is actually transmitted. We then briefly describe the concepts of super spreaders and super-spreading events, which help to explain how a relatively small group of people can have a significant impact on the transmission of the coronavirus. Brief descriptions of the findings of three recent research studies follow. These suggest that people with narcissistic and other “dark” personality traits, break public health restrictions. Finally, we draw attention to the limitations of the studies and provide some “takeaways”.
 
Developing and scaling vaccines is challenging

Although scientists look likely to produce a CoVID-19 vaccine much faster than anyone could have predicted, and governments have pre-purchased about 4bn doses of these for delivery at the end of 2020, developing a safe and effective vaccine at scale is challenging. The failure rate of vaccines that reach advanced clinical trials is as high as 80%. Some CoVID-19 vaccines in production that receive regulatory approval might only provide partial or temporary protection, others might require more than one dose to be effective. So, even if the accelerated vaccine development goes to plan and is successful, it is not altogether clear whether this would secure protection for enough people throughout the world to halt the spread of the virus in the medium term. Thus, it seems reasonable to assume that, behavioural techniques to slow or stop the spread of the coronavirus will be needed for some time yet, and people with narcissistic personality traits could reduce the effectiveness of these endeavours.
 

Narcissistic Personality Disorder

Narcissism is a pattern of grandiosity, a need for admiration and a lack of empathy. The condition has its genesis  in Greek mythology, and a beautiful and proud young man called Narcissus, the son of the river god Cephissus and the nymph Liriope. Many fell in love with Narcissus, but he only showed them disdain and contempt. When Nemesis, the goddess of retribution and revenge, learned of this she decided to punish Narcissus for his behaviour and led him to a pool where he saw his reflection in the water and fell in love with it. Narcissistic personality disorder (NPD) is rare. Although the term NPD has been used since 1968, only in 1980 was it officially recognized in the third edition of the Diagnostic and Statistical Manual of Mental Disorders, which is a taxonomic and diagnostic manual published by the American Psychiatric Association. Notwithstanding, in all probability we all know someone with narcissistic tendencies, which we often dismiss as just a “big ego” problem. And, if we are honest, at some point in our lives, we have demonstrated some narcissistic traits. The signs and symptoms of NPD include: (i) having an exaggerated sense of self-importance and a sense of entitlement, (ii) wanting constant, excessive admiration, (iii) expecting to be recognized as superior even without achievements that warrant it, (iv) exaggerating achievements and talents, (v) believing that you are superior and desiring to associate with equally ‘special’ people, (vi) having an inability or unwillingness to  recognize the needs and feelings of others, (vii) expecting special favours and unquestioning compliance, and (viii) taking advantage of others to get what you want. Although research in social and personality psychology has added significantly to our general understanding of narcissism, it has been one of the least studied personality disorders, mainly because of its low societal urgency and health costs. The causes of NPD are unknown, and the condition remains a controversial diagnosis. Some researchers think that overprotective or neglectful parenting styles may have an impact. Genetics and neurobiology also may play a role in the development of NPD. Given the challenges of diagnosing the condition, prevalence rates vary significantly. For instance, in the US, reported prevalence in the general population varies from 0.5% to 5%. NPD is less frequently identified in psychiatric settings, but more often seen in private clinical settings and applied to higher-functioning patients.
 
R number

In early 2020, during the height of the coronavirus crisis, politicians throughout the world and public health officials constantly referred to the R or R0 number to indicate the spread of the virus. As a consequence, most people now know that R refers to the average number of people one person with coronavirus is likely to infect. R is calculated through a combination of data and modelling, which includes hospital and intensive care admissions, people testing positive, deaths and surveys of people’s contacts. R indicates whether the number of infected people is increasing or decreasing. When R is above 1, the virus will grow exponentially in a population with no immunity. At 1, the disease remains steady. Below 1, the virus will gradually infect fewer people, until the epidemic dries up. However, in real life, some people with the disease infect many others, while others with the coronavirus do not spread the disease at all. This means that the R number hides significant differences between individuals and their impact on virus transmission.
K number

To compensate for this, epidemiologists use an additional metric referred to as K, which describes the pattern of CoVID-19 transmission. K is the statistical value, which indicates  the variability in the number of new coronavirus cases that each person has infected. A high K value (>5), tells us that most people are generating similar numbers of secondary cases. A low value for K (>1)  tells us that a small number of infected people can trigger significant numbers of new cases relatively quickly.
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Key to controlling CoVID-19

Epidemiologists believe the K number, or the role played by variable transmission of the coronavirus, is critical to controlling its spread. Notwithstanding, what makes controlling the transmission of the coronavirus more challenging is the fact that many highly infectious people are asymptomatic. According to research findings of a paper published in the June 2020 edition of The Annals of Internal Medicine, 40% to 45% of those infected by CoVID-19 display no signs or symptoms of the disease at all, which suggests that, “the virus might have a greater potential than previously estimated to spread silently and deeply through human populations”. Thus, understanding why and how the virus is transmitted is key to gaining control of the CoVID-19 pandemic and stopping a second wave of cases.
 
Super-spreaders

As we have suggested, there is wide variability in the behaviours of infected individuals and their subsequent roles in spreading the coronavirus. A paper published in the June 2020 edition of Wellcome Open Research analysed the spread of CoVID-19 from China and estimated the K value to be as low as 0.1.  This suggested that 80% of new coronavirus cases were caused by only about 10% of infected individuals. An infected individual who breaks the rules is likely to generate significantly more secondary cases that an infected person who does not broach public health protocols. The Wellcome paper demonstrates how a relatively small number of infected people who flout government guidelines could become ‘super-spreaders’ and cause CoVID-19 to quickly rebound, even if locally eradicated. Thus, identifying and tracking super-spreaders, is fundamental to preventing future outbreaks.
 
Super spreading events

Super spreaders are responsible for super spreading events, which are not well understood and are challenging to study. Although there is no universally agreed definition of a super spreading event, it is generally assumed to be an incident in which someone passes on the virus to six or more people. Examples of super-spreading events of CoVID-19 include outbreaks in Seoul nightclubs in South Koreameat packing plants in the US and overcrowded clothes factories in the UK.
 
Three studies

We now turn to the findings of three recent research studies, which suggest that some super-spreaders of CoVID-19 might be people with specific personality traits. The first study we describe is entitled, “Adaptive and Dark Personality Traits in the Covid-19 Pandemic”. It is published in the June 2020 edition of the Journal of Social Psychological and Personality Science and was carried out by Pavel Blagov, who is the director of the Personality Laboratory at Whitman College, USA. The second and third studies are Polish and both published in the July 2020 edition of  Journal of the International Society for the Study of Individual Differences. One is entitled “Adaptive and maladaptive behavior during the COVID-19 pandemic”, and was conducted by researchers from SWPS University of Social Sciences and Humanities, Poland. The third study is entitled, “Who complies with the restrictions to reduce the spread of COVID-19?”, which was carried out by researchers from the University of Warsaw.
 
The Whitman College Study

In late March 2020, Blagov surveyed 502 American adults, to assess their personalities and gauge how compliant they were with public health protocols for reducing the impact of CoVID-19 such as; social distancing, wearing protective gear or following basic hygiene rules. While the majority of participants reported adherence to public health restrictions, some did not. The  study found that individuals with the so-called "Dark Triad" personality traits (narcissism, Machiavellianism and psychopathy) were more likely to purposely disregard protocols intended to reduce the spread of the coronavirus. The respondents who showed disinterest in the recommended health procedures scored higher on sub-traits of meanness and disinhibition. According to Blagov, it is possible that rule breakers become super-spreaders of CoVID-19 and “have a disproportionate impact on the pandemic by failing to protect themselves and others”.  

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At the height of the pandemic, narcissists and others with dark personality traits tended to act contrary to public health recommendations. They showed less inhibition to risk and disregarded other people's safety; manifestations of which included, not covering themselves when sneezing or coughing in public, touching communal facilities, not staying at home, not keeping their distance from others and not washing their hands frequently. The  study concludes that, “there may be a minority of people with particular personality styles (on the narcissism and psychopathy spectrum) that have a disproportionate impact on the pandemic by failing to protect themselves and others.”
The  SWPS Study

These findings are supported by the  SWPS study, which is based on an online survey of 755 people (332 male and 423 female) between 15th and 29th March 2020, which was during the first month of the national CoVID-19 lockdown in Poland. The cohort was middle class with ages ranging from 18 to 78, (M = 45.83, SD = 14.98). Over 40% of the participants had either a high school or a university education.  Findings suggest that people with narcissistic or psychopathic tendencies were more likely to hoard essentials during lockdown mainly because they had a heightened sense of entitlement, which manifested itself in being greedier and more competitive.

Also, researchers suggest that participants with narcissistic personalities tend to be self-centred and lack empathy, and therefore more likely to exploit other people. People with psychopathic tendencies may be more cruel, deceitful and manipulative while coming across superficially charming.  According to Bartłomiej Nowak, the lead author of the study, narcissists are: (i) more impulsive, (ii) focused on self-interest, (iii) tend toward risk-taking and (iv) less likely to comply with measures to reduce the spread of the coronavirus.

 
The Warsaw Study

The Warsaw study set out to use the CoVID-19 pandemic to understand who complies with public health restrictions  to reduce the spread of the coronavirus. Researchers hypothesised that narcissistic and psychopathic personality traits of rivalry and lack of empathy may be associated with less compliance towards government imposed coronavirus restrictions. The study was based on an online survey carried out between 14th and 30th April 2020, which was at the height of the coronavirus crisis in Europe. There were 263 participants (27.8% male, 71.5% female, 0.8% “other”) aged between 18 and 80  (M = 28.96, SD = 10.64) and about half (49%) had a university education. 
 
The study’s findings support those of the previous two studies described above. Researchers found that compliance with public health guidelines to control CoVID-19 was low among participants who had narcissistic tendencies. Participants scoring low on agreeableness and high on aspects of narcissism and psychopathy were less likely to comply with public health restrictions. People with narcissistic traits had a sense of entitlement and perceived the restrictions as the Government forcing its will upon them.
 
Limitations of the studies

All three studies have limitations, which include being based upon relatively small samples. Data are cross sectional rather than time series and collected at the beginning of public health restrictions when it seems reasonable to assume that “people may be more likely to engage in prevention and adhere to restrictions”. The US and Poland are both developed economies with different cultures that might not be relevant for other regions of the world and, in the case of the two Polish studies, participants were drawn from a relatively homogeneous group.
 
Takeaways

Findings of the three studies described in this Commentary are not sufficiently robust to definitively say that people with narcissistic traits are super-spreaders of CoVID-19. Not everyone who defies coronavirus restrictions does so because of dark personality characteristics. Indeed, there are many factors at play in understanding behaviours during the coronavirus pandemic. Notwithstanding, from the evidence presented in the three papers, it seems reasonable to suggest that people with narcissistic tendencies, and who are asymptomatically infected with the coronavirus, could become super-spreaders and have a disproportionate impact on the transmission of CoVID-19.
 
#coronavirus #pandemic #coVID-19 #narcissism
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joined 4 years, 9 months ago

Lalor Plaza Medical Centre

Lalor Plaza Medical Centre
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We are a GP owned and operated medical practice committed to comprehensive patient care. We pride ourselves in our services to the community. If you’ve been looking for local medical centres Melbourne wide, your search ends here.


Phone Number:
03 9466 1488

Business Hours:
Monday - Friday 08:00 AM - 06:00 PM
Saturday 08:30 AM - 01:00 PM
Sunday 9:00 AM - 01:00 PM


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joined 4 years, 9 months ago

Lalor Plaza Medical Centre

Lalor Plaza Medical Centre
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We are a GP owned and operated medical practice committed to comprehensive patient care. We pride ourselves in our services to the community. If you’ve been looking for local medical centres Melbourne wide, your search ends here.


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joined 4 years, 9 months ago

Northland Medical Centre

Northland Medical Centre
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Are you looking for a bulk billing medical center in Melbourne that is open 7 days a week?

We would like to welcome you at Northland Medical Centre.


Phone Number:
03 9471 9987

Business Hours:
Monday - Friday 08:00 AM - 05:00 PM
Saturday 08:00 AM - 05:00 PM
Sunday 09:00 AM - 05:00 PM


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  • For the first time in medical history scientists have corrected the cause of Huntington’s disease (HD)
  • HD is a fatal congenital neurodegenerative disorder that causes uncontrolled movements, emotional challenges, and loss of cognition
  • Current treatments only help symptoms rather than slow the progression of the disease
  • Researchers from University College London (UCL)havesafely lowered the levels of toxic proteins in the brain that cause HD
  • Experts say this is the biggest breakthrough in neurodegenerative research for 50 years
  • Earlier, an American animal study successfully used a similar technique to “silence” the mutant huntingtin gene in mice brains
  • Gene silencing stops the gene from making any mutant protein but does not eradicate the mutant HD gene
  • More studies are necessary to show whether the UCL study will effectively change the course of HD
  • Gene editing is a game-changer in biomedical research, but it faces significant technical and ethical challenges

Huntington’s disease and gene silencing
 
In December 2017, scientists completed the first human genetic engineering study that targeted the cause of Huntington’s disease (HD) (also known as Huntington’s Chorea), and successfully lowered the level of the harmful huntingtin protein that irreversibly damages the brains of patients suffering from this incurable degenerative condition. Current treatments for HD only help with symptoms, rather than slow the disease’s progression. The study’s leader, Professor Sarah Tabrizi, director of the Huntington’s Disease Centre at University College (UCL) London’s Institute of Neurology, says, “The results of this trial are of ground-breaking importance for Huntington’s disease patients and families”. Tabrizi’s research followed an earlier American study, which successfully used a similar technique to “silence” the mutant huntingtin gene in mice brains.
 
This Commentary describes Huntington’s disease, the 2 studies to silence the huntingtin gene, and also the gene silencing technology, which underlies both studies.
 

Huntington's disease
 
Huntington’s disease (HD) is a fatal congenital neurodegenerative disorder caused by a mutation in the gene of a protein called huntingtin, which triggers the degeneration of cells in the motor control regions of the brain, as well as other areas. HD is one of the most devastating neurodegenerative diseases, which some patients describe as Parkinson’s, Alzheimer’s and Motor Neurone disease rolled into one. HD leads to loss of muscle co-ordination; behavioural abnormalities and cognitive decline. Generally if one parent has HD then each child has a 50% chance of inheriting the disease. HD affects both sexes and about 12 people in 100,000, but appears to be less common in people of Japanese, Chinese, and African descent. If a child does not inherit the huntingtin gene, s/he will not develop the disease and generally cannot pass it to subsequent generations. Although there is a wide variation in its onset age, the majority of HD patients are diagnosed in middle age. Currently there is no cure for the disorder: although drugs exist, which help manage some symptoms they do not influence the progression of the disease.
 
 Signs and symptoms
 
The characteristic symptoms of HD include, cognitive impairment, mood shifts, irritability, depression and behavioural changes. As the disease develops symptoms get progressively worse and include uncontrolled movements, cognitive difficulties and issues with speech and swallowing. HD typically begins between the ages of 30 and 50. An earlier onset form called juvenile HD occurs in people under 20.  Symptoms of juvenile HD differ somewhat from adult onset HD and include unsteadiness, rigidity, difficulties at school, and seizures.  
 
Diagnoses
 
A genetic test, together with a medical history and neurological and laboratory tests, support doctors in their diagnosis of HD. Genetic testing, which costs between US$250 and US$350, is both cost-effective and diagnostically precise, and is important to establish whether HD is present in a family because some other illnesses may be misdiagnosed as HD. The disorder is a model for genetic testing because HD is relatively common, its etiology is understood, and there is significant experience with its management. There are 3 main types ofHD genetic testing: (i) to confirm or rule out the disorder, (ii) pre-symptomatic testing, and (iii) prenatal testing. Persons at risk of HD often seek pre-symptomatic testing to assist in making decisions about marriage, having children, and career. Positive results can evoke significant adverse emotional reactions, so appropriate pre- and post-test counselling is important.
  
Treatment
 
Current treatments can only alleviate the symptoms of HD, and do not delay the onset or slow the progression of the disease. Until the findings of the Tabrizi study there was no treatment that could stop or reverse the course of the disorder. Tetrabenazine and deuterabenazine are drugs prescribed for treating the chorea associated with HD.  Antipsychotic drugs may also help to alleviate chorea and can be used to help control hallucinations, delusions, and violent outbursts associated with the disease. Drugs may be prescribed to treat depression and anxiety, which are relatively common among HD sufferers. Drugs used to treat HD may have side effects such as fatigue, sedation, decreased concentration, restlessness, or hyper-excitability, and only should be used when symptoms create problems for the individual.
 
The Emory Study

In June 2017 scientists from the Emory University School of Medicine in Atlanta, USA, published findings of an animal study in the Journal of Clinical Investigation, which used the gene editing technique CRISPR-Cas9 to “silence” the mutate huntingtin gene (mHTT) in mice brains.

Study leader Xiao-Jiang Li, professor and expert in molecular mechanisms of inherited neuro-degeneration, used adult mice engineered to have the same mutant Huntington's-causing gene as humans, and were already showing signs of the disease. Using CRISPR-Cas9 Xiao-Jiang introduced genetic changes in an afflicted region of the brain that prevented further production of the faulty huntingtin gene. After 3 weeks, researchers noted that the brain region where the vector was applied, the mice brains showed that the aggregated proteins had almost disappeared, and there was a concomitant improvement in their physical functions; although not to the levels of the control mice.

The Emory research team’s findings showed that CRISPR-Cas9 successfully silenced part of a gene that produces toxic protein aggregates in the brains of mice, and demonstrated that the technique holds out the possibility of a one-time solution for HD.
 
The UCL study
 
What the Emory study achieved in mice the UCL study achieved in humans. The UCL study of the huntingtin-lowering drug Ionis-HTTRx led by Tabrizi and sponsored by Ionis Pharmaceuticals, a US$6bn NASDAQ traded company based in Carlsbad, California, used a similar technique as the Emory study to “silence” the mutated huntingtin gene. The study, which had been in pre-clinical development for over a decade, enrolled 46 human patients with early HD in 9 study centers in the UK, Germany and Canada. Each patient received 4 doses of either Ionis-HTTRx or a placebo, which were given one month apart by injection into the spinal fluid to enable the drug to reach the brain. As the study progressed, the dose of Ionis-HTTRx was increased several times according to the ascending-dose study design.
Orphan drug

Ionis-HTTRx is a so-called antisense drug, which means that it inhibits the expression of the huntingtin gene and therefore reduces the production of the mutant huntingtin protein (mHTT) in patients with HD.  In January 2016 Ionis-HTTRx received orphan drug designation from the US Food and Drug Administration (FDA), and the European Medicines Agency. This is a special status given to drugs that are not developed by the pharmaceutical industry for economic reasons but which respond to public health need.
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UCL study extended

Ionis-HTTRx was found to reduce the amounts of the mutant huntingtin gene that caused HD in the patients tested. It was also found to have an acceptable safety and tolerability profile.  It is too early to call Tabrizi and her colleagues’ findings a “cure” for HD, as the study was too small and not long enough to demonstrate whether patients’ clinical symptoms improve over time. Long-term data are necessary to show whether lowering the mHTT will effectively change the course of the disease. Notwithstanding the study’s findings point to the prospect of effective future treatments.
 
As a result of the study’s success, Ionis’s partner, Roche, a Swiss multinational healthcare company, has exercised its option and paid US$45m to license Ionis-HTTRx and assume responsibility for its further development, regulatory activities and commercialization. A future open-label extension study is expected to assess the effect of Ionis-HTTRx on the progression of HD, and Ionis Phamaceuticals announced that all patients in the completed study would be offered a place in the extension study.
 
Gene silencing

Gene silencing, the technique used in the both the UCL and Emory studies, relies on the fact that cells do not directly copy DNA into protein, but instead make a rough copy from a chemical called RNA, which acts as a “messenger” carrying instructions from DNA that control proteins. Gene silencing techniques target the RNA message: cutting it up, and thereby stopping the cell from making the mutant protein. However, even if gene silencing works to reduce the level of the harmful huntingtin gene, as it did in both the UCL and Emory studies, it does not change the DNA, and a HD mutation carrier still has the mutant HD gene. The “silencing” simply stops the gene making any mutant protein. Rather than silencing the mutant huntingtin gene it would be more efficacious if scientists could cut out the extra copies of the mutation that causes the disease.
 
CRISPR

CRISPR allows scientists to easily and inexpensively find and alter virtually any piece of DNA in any species. The technology potentially offers a cure for a number of incurable diseases, but its use in humans is not only ethically controversial, but also challenged by a need to find efficacious ways to deliver gene editing techniques inside the human body. Notwithstanding, there is a global race to push the technique to its limits.
 
Despite the potential of gene editing technology, scientists have encountered significant delivery challenges in using CRISPR techniques in humans for HD. Because CRISPR therapies are based on big protein molecules, they cannot be taken as a pill, but have to be delivered into the brain using injections, packaged into viruses, or similar technology. This presents delivery challenges, and the efficacy of gene editing therapies for neurodegenerative disorders is predicated upon effective delivery.

 
Takeaways

The UCL study significantly reduced the relevant protein levels in the cerebrospinal fluid of patients with Huntington’s. CRISPR’s success with HD raises the possibility that the technique might work for other neurodegenerative disorders such as Alzheimer’s. However, the genetic causes of Alzheimer’s and other neurodegenerative disorders are less well understood and more complex than Huntington’s, which makes them potentially more challenging. Further there are still significant scientific and ethical challenges to be overcome before gene-editing technology becomes common practice.
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