Current research on Huntington's

Research is underway to find disease-modifying drugs and new treatments for the symptoms of Huntington's disease.

Exciting progress has been made in identifying potential ways of slowing down or halting the disease. For example switching off the faulty gene that causes Huntington's disease.

There some people who have inherited the disease but have not yet developed symptoms. This group of people who are unaware they carry the disease, may have had children and passed on the disease without realising. Hence it's important to get tested if you have a family history of the disease.

Referencing

http://libweb.anglia.ac.uk/referencing/harvard.htm I structured my bibliography according to the referencing examples in this website. It showed different referencing layouts for information obtained from different sources such as textbooks and websites.

What research advances have the Brain Research Centre made in Parkinson's?

This website http://www.brain.ubc.ca/research/neurodegeneration.htm specifically talks about 2 of the diseases that I'm doing: Parkinson's and ALS. I might add some more information that i find from this website in my essay, for example what research advances the Brain Research Centre has made in Parkinson’s disease 

New model for ALS

I found another website (http://www.news-medical.net/news/20110812/New-model-for-amyotrophic-lateral-sclerosis.aspx) that talks about the development of a new model for ALS


The researchers derived astrocytes (cells) from patients of ALS, and found that the cells secrete toxic factors which cause nerve cells to degenerate. A similar mechanism has been found in mouse models of ALS. Researchers also found from further experiments that inflammatory responses may play a role in this toxicity. For example they analysed 84 genes involved in inflammation, and found that 35-60 percent of the genes showed increased activity in ALS astrocytes compared to controls.


The results of other experiments suggested the need for further investigation of SOD1 and astrocytes as targets for therapy.(23)

(24)

Cell recycling system damaged in ALS

A breakdown of a recycling system in cells appears to be the underlying cause of ALS (most common form of motor neuron disease)


The breakdown occurs in the recycling system in the nerve cells of the spinal cord and the brain. In order to function properly, the protein building blocks in the cells need to be recycled. But in ALS, that system is broken. The cell cannot repair or maintain itself and becomes severely damaged.

The scientists found a protein, ubiquilin2, which should be directing the recycling process, does not work in people with ALS. This means the damaged proteins accumulate in nerve cells of the spinal cord and brain, causing their degeneration.


The researchers, from Northwestern University Feinberg School of Medicine, found this breakdown occurs in all three forms of ALS.


It's been known for some time that the waste and recycling system in motor neurons is damaged, but this is the first time that there has been direct proof. Now researchers can test for drugs that would regulate this protein pathway, so it functions as it should in a normal state. This discovery provides researchers with an exciting new avenue to explore as they search for an effective treatment.(22)

Research programme focusing on Parkinson's disease

Three new research programmes focusing on neurodegenerative diseases, Alzheimer's, Parkinson's and motor neuron disease, have received major funding from the Wellcome Trust and the Medical Research Council.

Professors Nicholas Wood, John Hardy and Anthony Schapira at the Institute of Neurology, London, outline the changing face of Parkinson's disease research and their hopes to fully understand its causes and effects at the genetic level.

Another study describes the dramatic improvement in Parkinson’s disease symptoms following intranasal delivery of stem cells to rat brains: successful intranasal delivery of stem cells to the brains of rats with Parkinson’s disease yielded significant improvement in motor function (movement) and reversed the dopamine deficiency characteristic of the disease.

The promising findings, reported in Rejuvenation Research, a peer-reviewed journal published by Mary Ann Liebert, highlight the potential for a non-invasive approach to cell therapy delivery in Parkinson’s disease, a safer and effective alternative to surgical transplantation of stem cells. In this groundbreaking study, mesenchymal stem cells (MSCs) delivered via the nose preferentially migrated to the brain and were able to survive for at least 6 months. Substantial improvement in motor function, up to 68% of normal, was reported in the MSC treated rat model of Parkinson’s disease. Levels of the neurotransmitter dopamine were significantly higher in affected rat brain regions exposed to MSCs compared to the non-treated brain regions.(21)

Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types, including: osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells) (17)

But there are still ethical issues on usage of embryonic stem cells, which are the most useful stem cells for treatment. The problem is that when stem cells are obtained from living human embryos, the harvesting of such cells necessitates destruction of the embryos.

In contrast to research on embryonic stem cells, non-embryonic stem cell research has already resulted in numerous instances of actual clinical benefit to patients. For example, patients suffering from: Parkinson’s disease, autoimmune diseases, stroke, anemia, cancer, immunodeficiency and corneal damage experienced improved function following administration of therapies derived from adult or umbilical cord blood stem cells. The long-held belief that non-embryonic stem cells are less able to differentiate into multiple cell types or be sustained in the laboratory over an extended period of time rendering them less medically-promising than embryonic stem cells, has been repeatedly challenged by experimental results that have suggested otherwise. (19)

Progress in stem cell research for treating Parkinson's

The main treatments for Parkinson's are drugs that aim to control the symptoms by increasing the levels of dopamine that reach the brain and stimulating the parts of the brain where dopamine works. Some patients have wires surgically implanted into their brains that deliver electrical pulses to alleviate movement problems.

For around a decade, scientists have been trying to re-grow nerve cells lost in

neurodegenerative diseases such as Parkinson's, Alzheimer's and amyotrophic lateral sclerosis (ALS) from stem cells. However experiments in which dopamine neurons were created from mouse stem cells have not been successfully reproduced in humans. There have also been safety concerns, with signs that dopamine neurons developed from human stem cells can trigger the growth of tumours. As a result, clinical trials in humans have yet to start.

Dr Studer and his colleagues, whose work is published in the journal Nature, found the specific chemical signals required to nudge stem cells into the right kind of dopamine-producing brain cells.

In a series of experiments, the team gave animals six injections of more than a million cells each, to parts of the brain affected by Parkinson's. The neurons survived, formed new connections and restored lost movement in mouse, rat and monkey models of the disease, with no sign of tumour development. The improvement in monkeys was crucial, as the rodent brains required fewer working neurons to overcome their symptoms. This study has shown for the first time that it is possible to transplant nerve cells that work from human stem cells. (19)

Dopamine-producing nerve cells derived from embryonic stem cells and implanted into the brain of a monkey with Parkinson's disease

A discussion with my supervisor

I spoke with my supervisor and took notes of things I have to do. She  advised me to keep a record of my progress on my blog and that I should try to find information about the diseases from a variety of sources. So I might find a film or documentary based on one of the nuerodegenerative conditions to watch.

Working on essay and presentation

I'm working on my essay and presentation. So far I've only written about one neurodegenerative disease. which I might show my supervisor to discuss and improve on it. My presentation has to be about 10 minutes long. I've just prepared an introduction. And according to my google calendar I have to hand in my 1st essay draft to my supervisor on the 15th of December.

Essay plan

I wanted to make a plan or summary of what I'm going to talk about so I don't get confused about the layout when I start writing up my report. I am worried that talking about 3 diseases will be unnecessary as they're quite similar to each other and I might end up repeating the same information in the report. If I decide to change my topic idea in the next few days I'll need to make a new plan.

Using google calendar

I made new deadlines on my google calendar.

Huntington's disease

Huntington’s disease is a hereditary neurological disorder of the central nervous system that causes progressive degeneration of cells in the brain, slowly impairing a person's ability to walk, think, talk and reason.

• Huntington’s Disease is also called Huntington’s Chorea.  Chorea means dance which refers to the jerky symptoms of patients with the disease.
• Huntington’s Disease was first discovered by Dr. George Huntington.  The disease is named after him.

How do you get Huntington’s Disease?

Huntington's disease is caused by a genetic defect on chromosome 4. The defect causes a part of DNA, called a CAG repeat, to occur many more times than it is supposed to. Normally, this section of DNA is repeated 10 to 28 times. But in persons with Huntington's disease, it is repeated 36 to 120 times. Scientists are not sure how this works, but the extra copies cause the accumulation of toxic protein in your brain.  The more copies you have, the sooner you will get Huntington’s Disease and the more severe your symptoms will be.    

As the gene is passed down through families, the number of repeats tend to get larger. The larger the number of repeats, the greater your chance of developing symptoms at an earlier age. Therefore, as the disease is passed along in families, symptoms develop at younger and younger ages.

The tragedy is that by the time symptoms appear, the person has often had a family and may have passed on the gene to their children. Each person whose parent has Huntington's disease has a 50 per cent chance of inheriting the gene, and everyone who inherits the gene will at some stage develop the disease.

The disease can't be prevented from developing if someone has the faulty gene. To inherit the illness, the gene only has to come from one parent, making it autosomal dominant.

The gene for Huntington's disease can be detected with a blood test that can determine whether someone has the faulty gene and help them in their family planning.

Is there a cure for Huntington’s Disease?

No there is not a cure for Huntington’s Disease.  There is not even a treatment that will help slow the progression of the disease down.  However, there is medicine that will make the patient more comfortable, that will help reduce the symptoms. It’s important for people with Huntington’s Disease to stay in shape.  This helps reduce jerky movement and, like most things, people who exercise tend to do better than those who don’t.  Physical Therapy is very important as well as speech therapy to help the patient lead a more normal life. Huntington’s Disease patients need assistance performing the simplest of tasks.  That is why 24-hour care is eventually needed. Since the risk of getting Huntington’s Disease is so high if one of your parents has the gene, most people who know they have the gene chose to adopt so that their children won’t inherit the disease.

Symptoms

There is a long list of symptoms for Huntington’s Disease.  The disease causes behavioral changes such as irritability, moodiness, and antisocial behaviors.  It causes restlessness, fidgeting, paranoia, and hallucinations.  People with Huntington’s Disease lose their memory and their judgement.  They experience personality changes, confusion, disorientation, anxiety, stress, and tension.  They also lose their ability to speak.  

    

Huntington’s disease also effects people’s motor skills.  They walk unsteadily and suffer from quick and sudden jerking movements of their limbs.  They also have difficulty swallowing. If a child suffers from Huntington’s Disease symptoms they will have slow movements, tremors, and rigidity.   Overall, people with Huntington’s Disease lose the ability to care for themselves and to interact with others.  They have the potential to injure themselves of others and they have increased risk of infections.  Many people who suffer from Huntington’s Disease also suffer from depression.  A lot of Huntington’s Disease patients’deaths’ are caused by suicide and not the actual disease. Huntington’s Disease is a horrible condition that makes day to day life impossible.  Within 15 to 20 years after you see symptoms, this disorder becomes fatal.

Ethical issues

There are ethical concerns related to prenatal genetic testing or preimplantation genetic diagnosis to ensure a child is not born with a given disease. For example, prenatal testing raises the issue of selective abortion, a choice considered unacceptable by some. Using preimplantation testing for HD requires twice as many embryos to be used for in vitro fertilization, as half of them will be positive for HD. As it is a dominant disease, there are difficulties in situations in which a parent does not want to know his or her own diagnosis. This would require parts of the process to be kept secret from the parent.

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the death of both upper and lower motor neurons in the motor cortex of the brain, the brain stem, and the spinal cord.

ALS is also known as Lou Gehrig's disease after the famous baseball player who died from this condition.

Motor neurons are nerve cells that control muscle movement. Upper motor neurons send messages from the brain to the spinal cord, and lower motor neurons send messages from the spinal cord to the muscles allowing movement. Motor neurons are an important part of the body's neuromuscular system.

Etymologically:

Amyotrophic- lack of muscle nourishment

Lateral- portion of the spinal cord where motor neuron damage occurs

Sclerosis- neuronal degeneration causes scarring and hardening of tissue.

As a result of neurons degenerating this condition leads to muscle weakening, twitching, and an inability to move the arms, legs, and body. Hence a debilitating disease. When the muscles in the chest area stop working, it becomes hard or impossible to breathe on one's own.

ALS does not affect the senses (sight, smell, taste, hearing, touch). And it only rarely affects bladder or bowel function, or a person's ability to think or reason.

The cause

For patients without a family history of the disease, which includes -95% of cases, there is no known cause for ALS. There is a known hereditary factor in familial ALS (FALS), where the condition is known to run in families, although this accounts for only around 5% of all cases. An inherited genetic defect on chromosome 21 (coding for superoxide dismutase) is associated with approximately 20% of familial cases of ALS.This mutation is believed to be autosomal dominant. 

Treatment: There is no known cure for ALS. The first drug treatment for the disease is a medicine called riluzole. Riluzole slows the disease progression and prolongs life.Treatments to control symptoms are also helpful:

• Baclofen or diazepam may be used to control spasticity that interferes with daily activities.

• Trihexyphenidyl or amitriptyline may be prescribed for people with problems swallowing their own saliva.

Physical therapy, rehabilitation, use of braces or a wheelchair, or other orthopedic measures may be needed to maximize muscle function and general health.

Choking is common. Patients may decide to have a tube placed into their stomach for feeding, called a gastrostomy.

A nutritionist is very important. Patients with ALS tend to lose weight. The illness itself increases the need for food and calories. At the same time, problems with swallowing make it hard to eat enough.

Breathing devices include machines that are used only at night, and constant mechanical ventilation.

Support Groups: Emotional support is vital in coping with the disorder, because mental functioning is not affected. Groups such as the ALS Association may be available to help people who are coping with the disorder.

Research 

Scientists are seeking to understand the mechanisms that trigger selective motor neurons to degenerate in ALS and to find effective approaches to halt the processes leading to cell death. 

This work includes studies in animals to identify the means by which SOD1 mutations lead to the destruction of neurons. The excessive accumulation of free radicals, which has been implicated in a number of neurodegenerative diseases including ALS, is also being closely studied. 

In addition, researchers are examining how the loss of neurotrophic factors may be involved in ALS. Neurotrophic factors are chemicals found in the brain and spinal cord that play a vital role in the development, specification, maintenance, and protection of neurons. Researchers hope to find the cause or causes of motor neuron degeneration in ALS and develop therapies to slow the progression of the disease.

Stem Cell Therapy

One of the proposed future therapies for ALS is stem cell therapy, where stem cells harvested from either human bone marrow or preserved umbilical cord blood can be implanted in the patient to replace damaged cells. In a neurodegenerative disease like ALS, cells adjacent to motor neurons in the surrounding area of the body become damaged as well, causing widespread cell death and a rapid decrease in normal functioning in the patient. These stem cells would be directed to the damaged area and provide necessary growth factors to the damaged or dying motor neurons and other cells.

This breakthrough has raised several concerns that could halt the progression of research in this field. the many controversial ethical implications that have followed the stem cell debated for years must be taken into consideration. Although the implantation of the stem cells into the site of damage has been very successful in animal models, there has been little evidence that they connect with their desired targets (motor neurons to muscle fibres). Motor neurons must connect to muscle fibres over distance of up to 3 meters and making this connection is vital to the regeneration of activity. An additional concern in stem cell therapy research is the possibility of immuno-rejection of foreign cells by the body's immune system.

what may have appeared to be impossible several years ago of particular relevance to ALS is whether stem cells can be directed to generate motor neurons. Research in Dr. Tom Jessell's laboratory demonstrates that mouse embryonic stem cells can indeed be differentiated into motor neurons and when introduced into the spinal cord of embryonic chicks, motor axons form contacts with skeletal muscle. This promising research demonstrates the progress that has recently been made. Scientists acknowledge that the leap from an embryonic chick to a human adult is huge and currently an unobtainable goal. However, the promise of stem cells as vehicles for trophic support for dying neurons is possibly a more feasible goal and many studies are focusing on this approach. Several studies have shown that embryonic stem cells in culture can be genetically modified. Using this technology, stem cells can be modified to deliver genes and other factors to dying motor neurons. More research is needed in this area.

There are currently no human clinical trials however a few unpublished efforts have been disclosed using bone marrow and cord blood stem cells in humans and are in very early stages. With all the excitement and possibilities stem cells have to offer as a therapy, it is critical that scientists  and clinicians are cautious and plan rigorous studies. If ethical concerns can be properly addressed and continued research regarding the innervation of nerve projections sees progress, a human-model clinical trial can take place in the near future.

Finding a Plan

After a few discussions with my supervisor I decided on preparing a power point presentation and an essay. She also advised me to prepare a plan for my project by using google calendar and so I did: (https://www.google.com/calendar/render?hl=en&pli=1) I will use this as a guide for my project.

What causes Parkinson's disease (what changes happens in the brain)

Within our brains the basal ganglia is one of the body's motion control centre. Inside the basal ganglia is a region called the striatum which allows us to direct our body's movements to accomplish what we want to do. Below the striatum is an area called the substantia nigra. This area is rich in cells that produce a chemical called dopamine, these dopamine producing cells have long wire like projections that connect them to the striatum. When the substantia nigra sends a signal these cells release dopamine into the striatum. Inside the striatum dopamine helps the striatal cells receive the brains motion control messages.


In the healthy brain plenty of dopamine is available to help these brain cells do their job. In Parkinson's disease the dopamine producing nerve cells in the substantia nigra die. As a result the long wire like projections of these cells disappear unless dopamine is provided to the striatum to help movement messages get through. This leads to the cardinal features of Parkinson's disease, for example slowness of movement, tremor and rigidity.
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Parkinson's disease is a degenerative disease, which means that these symptoms will get worse overtime as more dopamine cells are lost. PD. also causes symptoms that aren't movement related, including: 

• Problems with gait and balance
• Cognitive dysfunction
• Depression
• Constipation

Scientists are not sure what causes these symptoms and no treatments effectively address them. Research is on going to better understand these symptoms as well as the dopamine degeneration seen in PD. This will help us develop treatment to improve patients quality of life.(5)

Bibliography

1. http://www.holisticonline.com/images/PD-ama-schematic1.GIF
2. http://www.holisticonline.com/remedies/parkinson/pd_brain.htm
3. http://video.about.com/seniorhealth/Parkinson-s-Disease.htm
4. http://www.michaeljfox.org/about_ourMission.cfm
5. http://www.michaeljfox.org/living.cfm#
6. http://www.patient.co.uk/health/Parkinson's-Disease.htm
7. http://speakcampaigns.org/images/PD/basal_ganglia_detail-web.gif
8. http://blog.amsvans.com/wp-content/uploads/2011/07/alsnerves.gif
9. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001708/
10. http://www.alsa.org/research/about-als-research/primer-on-stem-cells.html
11. http://kidshealth.org/kid/grownup/conditions/als.html
12. http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/detail_ALS.htm
13. http://lh6.ggpht.com/_XNVS6Bkyaac/TOkRRJ3mmI/AAAAAAAABMo/Hr5mTLgQz7w/alsdiagram3.jpg
14. http://stemcell-treatments.blogspot.com/
15. https://sites.google.com/a/conncoll.edu/neurobiology-of-disease/home/amyotrophic-lateral-sclerosis-als---kelsey-fredericks-and-paige-landry
16. http://en.wikipedia.org/wiki/Amyotrophic_lateral_sclerosis
17. http://en.wikipedia.org/wiki/File:Mesenchymal_Stem_Cell.jpg
18. http://www.guardian.co.uk/science/2011/nov/06/stem-cells-brain-parkinsons-disease
19. http://cbhd.org/stem-cell-research/overview
20. Nardi, N. Beyer; da Silva Meirelles, L. (2006). "Mesenchymal Stem Cells: Isolation, In Vitro Expansion and Characterization".
21. ScienceDaily. Retrieved December 5, 2011, from http://www.sciencedaily.com /releases/2011/02/110208163504.htm
22. http://www.bbc.co.uk/news/health-14591364
23. http://www.news-medical.net/news/20110812/New-model-for-amyotrophic-lateral-sclerosis.aspx (NIH/National Institute of Neurological Disorders and Stroke)
24. http://jcb.rupress.org/content/187/6/761/F2.large.jpg

Medical treatment for Parkinson's

Treatment is aimed at abolishing as far as possible the symptoms and disabilities caused by Parkinson's. But these dugs cannot prevent brain cell degeneration.
What the available drugs will do is to reverse the symptoms by replacing the essential chemicals, such as dopamine, necessary for the normal transmission of nerve impulses and control of movements.


At an early stage most patients should be referred to a hospital specialist, usually a neurologist in order to confirm the diagnosis, and to obtain advice about the immediate and future prospects of treatment.


Drug treatment: Patients with Parkinson's have a deficiency of essential dopamine and the excess of acetylcholine. Early treatment consists of drugs called anticholinergics, which diminish acetylcholine and work to restore the balance with dopamine. These drugs are valuable for treating early tremors and rigidity. Also good at controlling salivation and drooling. However these drugs are generally used in younger patients who don't have the added complications of the elderly. Drugs include: Orphenadrin and Benzhexol
Other drug treatments include: levodopa drugs (for moderate and severe Parkinson's), dopamine agonists and selegiline (weak anti-parkinsonian drug)


Combinations of levodopa with carbidopa or benserazide are the most effective drugs. Unwanted side-effects can be reduced by altering the drug dose and timing.
In Parkinson’s disease, degeneration of parts of the basal ganglia causes a lack of dopamine within this part of the brain. The basal ganglia are thus prevented from modifying the nerve pathways that control muscle contraction. As a result, the muscles are overly tense, causing tremor, joint rigidity, and slow movement. Most drug treatments increase the level of dopamine in the brain or oppose the action of acetylcholine.

(1)

However all drug treatments also have their own side-effects, some examples are nausea and vomiting, fainting, Dyskinesia and dystonia, mental confusion and hallucinations and aggressive behaviour.

Gene Therapy: holds considerable potential for the treatment of central nervous system disease. It aims to introduce a protein, which can protect against cell damage or permit the physiological delivery of a deficient neurotransmitter. The strategies for gene therapy techniques have expanded toward the use of factors that induce nerve cell growth in enhancing cell function or preventing cell death.


Surgery is another treatment that consists of either destruction of tiny parts of the brain (stereotactic surgery) or transplantation of dopamine-producing tissue into the brain. Surgery for Parkinson's is rarely recommended. Examples: nigral transplants and fetal tissue transplant. There are ethical problems in obtaining and using fetal donor tissue, and the long-term benefits are not yet known.


However, it's encouraging that robust survival of fetal nigral implants can be achieved within the human brain; these can give a new nerve supply to the damaged nerve cells in the basal ganglia. But it's not known whether those agents that primarily cause the disease will also destroy the graft.


There is far more to the treatment of the patient than just the administration of drugs, for example Physiotherapy, occupational therapy and speech therapy are valuable for an effective treatment.


Simple physical movements, such as getting out of a chair, may become increasingly difficult for patients as physical disabilities hinder action. In this case regular exercise is beneficial.
I obtained information from a range of books called: Family doctor guide to Parkinson's disease, Living well with Parkinson's disease and explaining Parkinson's.


Also as I was searching for Parkinson's related videos I found one about Actor Michael J Fox who also suffers from Parkinson's. The video explains his journey with this condition. Currently he has his own campaign called "Michael J Fox Foundation for Parkinson's Research". The website for this campaign http://www.michaeljfox.org/ includes a section called 'living with Parkinson's' that has useful information on how Parkinson's disease affects the brain. 

The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson’s disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson’s today.

Michael J Fox believes that if there is a concentrated effort from the Parkinson’s community, elected representatives in Washington, DC, and the general public, researchers can pinpoint the cause of Parkinson’s and uncover a cure within our lifetime. The foundation works with leading Parkinson's experts to determine the most promising areas for research. It's inspiring that Fox has played strongly against his Parkinson's disease by aiming to find a cure, this requires hard work and compassion for the other sufferers of Parkinson's. But also makes the possibility of finding a cure with many other passionate researchers around the world more likely.

Fox teamed up with Nike to produce the Nike Mag shoes. 1500 pairs of Nike MAG shoes were auctioned on eBay to benefit his foundation. An astonishing $4.7 million was raised which will go to the Foundation’s research programs to help speed the search for a cure for Parkinson’s.(4)

The Human Brain

I started reading The Human Brain and its disorders. It covers a whole range of neurodegenerative conditions and the basics about the brain. The book also includes a few case studies for each disease.
Some information I found from websites include: Parkinson’s disease is a progressive condition caused by the decreased production of dopamine when the area of the brain which produces a neurotransmitter is substantively damaged. The neurotransmitter, dopamine, is responsible for the communication of electrical impulses that control muscle motion.

Although physicians are well aware of why the symptoms of Parkinson's disease occur, they are unable to determine why that area of the brain becomes damaged in the first place.