The research team found that hNPCs genetically modified to over-express GDNF were able to survive the transplant and produced GDNF for three months. The possibilities of this method can therefore be applied to Huntington’s and an ongoing study to do with neural transplantation in HD patients [13] is producing similar results.
An article published in The Open Neurology Journal in 2011, described Deep Brain Stimulation in Huntington’s disease: The Current Status by Dagmar Zeef, Frédéric Schaper, Rinske Vlamings, Veerle Visser-Vandewalle and Yasin Temel [14]. More specifically this study looks at GPi Pallidotomy as deep brain simulation. Pallidotomy is a surgical procedure where an electrical probe I placed onto the Globus Pallidus Internus (one of the basal ganglia) of the patients brain. The probe is the heated to 60-70 degrees Celsius to destroy a group of cells. The probe destroys lesions which cause chorea and other symptoms involved in Huntington’s disease. The study was based on 5 different patients and their improvement after GPi-DBS surgery. Their percentage improvement was based on their UHDRS-score (Unified Huntington’s Disease Rating Scale) before and after the surgery. The follow up period varied from 8 -48 months between patients. UHDRS gives a measurement of improvement for 5 symptoms of Huntington’s disease.
How effective is this data?
The effectiveness of neural transplants was studied in ‘Effect of foetal neural transplants in patients with Huntington’s disease 6 years after surgery: a long-term follow-up study Anne-Catherine Bachoud-Lévi, Véronique Gaura.’[13]
Fig.1 shows patients 1, 2 and 3 and there UHDRS (Unified Huntington’s Disease Rating Scale). The UHDRS test was taken every year for six years and tested, mainly, the progress of chorea in the patients. This test showed that over the six year period, the patient’s mental degeneration was decreased and over the six year period, generally, all 3 patients improved.
Fig.2 shows the score of all the patients of the neural transplants in the study. It shows their UHDRS score and the time it takes them to complete the test. This shows that patients 4 and 5 continued to deteriorate despite the neural grafts. This therefore shows that although 3 of the 5 patients improved, 2 did not. This means that this solution is relatively effective and has potential. However two of the patients continued to decline and the neural transplants did not work. Later on in the study it was also discovered that after the six year period the other three patients declined as well. It can be said then that neural transplants provide an effective, yet temporary treatment. It can add essential years to the patient’s life however, in terms of a permanent treatment or cure for Huntington’s; neural transplants are not a suitable treatment, at this time, for the patient’s lifetime.
The effectiveness of Pallidotomy was researched in Deep Brain Stimulation in Huntington ’s Disease: The Current Status by Dagmar Zeef, Frédéric Schaper, Rinske Vlamings, Veerle Visser-Vandewalle and Yasin Temel [14]. Fig.3 shows 5 patients and details their GPi surgery and other variables that may be considered. It describes the age of the patients when they started to present symptoms and when they had the surgery, their symptoms, their UHDRS score before and after the surgery and the percentage improvement. It also describes the other treatments and medication Pallidotomy can be seen, from this data, as an effective treatment. Regardless of the other differences and variables between patients, all patients improved after Pallidotomy surgery. However the table also shows side effects of the treatment. After surgery, patients had increased or new symptoms such as bradykinesia (slowed movements) or a decline in glottic function. This may be attributed to the surgery or just simply the normal progression of the disease. In either case, this makes the effectiveness of the surgery seem less. Still though, as all patients of any age, gender and any stage of the disease did improve, this treatment can be seen as effective but not permanent.
Social and Ethical implications of the Treatments of HD
Ethical - There are many ethical implications surrounding the treatments outlined earlier. Pallidotomy, and more importantly, neural transplantation is physical manipulation of the brain. Psychiatric symptoms of HD may prevent the patient from making the decision to have major brain surgery and may depend on the next of kin to make this important decision. Questions are then raised of the motives of the next of kin, which may not be in the patient’s best interest. Another ethical issue originates from the nature of the neural cells. A book written in 1999 outlines the ethical issues in medicine and describes possible ethical issues with neural transplantation [17]. Page 463 of this book raises the issue of foetal donor cells and if they should be used. There are many people who believe that the use of foetal cells is wrong as the foetus is still considered a life for many people. This viewpoint may be down to personal or religious beliefs. For example many Catholics believe that ‘it could be argued that abortion is unacceptable and that the use of the resultant material is tantamount to complicity in the act of elective abortion.’[17]
Economic - Huntington’s disease is a degenerative disorder that prevents most people from living a normal life and working. According to the national institute of health, in 1989 the average cost per year of movement disorders were around 3 billion dollars [18]. This includes costs for medical care and the income lost due to the inability to work. These figures indicate and imply that the cost of treating Huntington’s may be too much as all the treatments available are temporary treatments, not cures.
The benefits and risks to Humans
There are several advantages and benefits to humans. One of these is that neural transplantation has shown to be an effective treatment for Huntington’s disease and most patients who underwent the transplant had recovered most mobility lost from the disease. If not only for a few years this treatment can be seen as advantageous to humans [13]. Neural transplantation’s main advantage is that it replaces neurons lost by damage Huntington’s disease causes. This is dissimilar to GPi as Pallidotomy only destroys damaged brain tissue. Replacing them however improve the patient’s brain function and does reduce involuntary movements and also increase the speed and stability of the patient’s voluntary movements
Pallidotomy has also shown to be advantageous in the aforementioned study as there was a significant percentage improvement in all patients for all symptoms [14]. Pallidotomy can be used for many diseases and for many symptoms of HD. Pallidotomy is very advantageous in this way as it can treat diskinesia (difficulty in performing voluntary movements) or bradykinesia (the general slowness of movement especially in tasks requiring fine motor control).
There are however some disadvantages and risks. Neural transplantation is major brain surgery and is usually irreversible or only reversible through another surgery. Like a lot of transplants, neural transplants need donor stem cells, usually from a foetus, and may not be available to all with Huntington’s disease. As the effects of neural transplantation wear off after 2-6 years it could be seen that the risks of major surgery may outweigh the benefits [13]. With both neural transplantation and GPi being invasive surgeries which remove the top of the skull, the risk of infection is massive. Deaths on the surgery table are also down to allergic reactions of anaesthetics. With 13.16% of selected infections resulting from medical care led to death in the US 2000-2002 and 1.44% of complications of resulted in death in the US 2000-2002. [12]
Alternative treatments
Surgery is not available to all HD patients and is potentially life threatening so we must look at other treatments available.
Medication
Most people with HD often have depression and mood swings. Medications are prescribed to prevent depression and mood swings, and to stop choreic involuntary movement. SSRI and tricyclic antidepressants such as fluoxetine and nortriptyline are often given patients to prevent mood swings and depression. Benzodiazepines, such as clonazepam and diazepam are also given to suppress involuntary movements. Although this is not a permanent cure and the patient does need a daily regiment of pills, most people respond well to the medication and most of the involuntary movements are suppressed. However diazepam and clonazepam both have side effects. Diazepam can cause drowsiness and pain, whereas clonazepam can cause incontinence.
Therapy
Different therapists and specialists can often help to manage various symptoms:
Speech and language therapists can help improve your communication and help you to swallow.
Dieticians can advise on adequate calorie and nutrient intake to stop weight loss.
Occupational therapists can provide you with equipment to help you eat, such as non-slip mats and straws, and help make your home safe by adapting it to your needs.
Physiotherapists can help with any balance or
musculoskeletal problems.
Pre-Implantation Genetic Diagnosis (PIGD/PGD)
PIGD is the method of determining whether an embryo will have the faulty gene before it is born. There are many steps to this process. Firstly the mother’s and father’s gametes are combined into a zygote outside of the womb (In-vitro fertilisation). The developing embryo (egg) is then tested for the genetic condition. If the embryo does not have the condition the fertilised egg is placed in the woman’s womb for pregnancy. If the embryo is likely to have the condition, it is usually discarded. Whatever the choice of the parents, to keep the embryos or not, the parent has enough information to make the right decision.
Evaluation of Sources
Reference 14 is an article from the Open Neurosurgery Journal published in 2011 titled ‘Deep Brain Stimulation in Huntington’s disease: The Current Status.’ Being published in the Open neurosurgery journal means that it is endorsed by it. Although this is not a randomised study, it is a controlled study which investigates the feasibility and effectiveness of DBS (Deep brain stimulation) as a treatment for Huntington’s disease. This study has been conducted and written about by knowledgeable experts in their own field and their research teams. This study does not involve a large sample size making it difficult to draw general conclusions, However as it is being used to show a possible new treatment and its effectiveness for treatment worldwide , I therefore think that this is a very reliable source and the results of this study were used as background and support for my report.
Reference 17 is a book titled ‘Theoretical Medicine and Bioethics: ’ by G.J Boer, Ethical Issues in Neurografting of Human Embryonic Cells’ which outlines the possible ethical issues in neurografting using human embryonic cells. Although the book was written by a large amount of professionals, G.J Boer was the only one to author ‘’ pages 461-476. This therefore decreases the reliability as collaboration with other professionals would demonstrate that Boer is speaking the truth. This book was published in 1999 which means that it does not contain any relevant data taken after 1999 which decreases the validity. It was released with a series of books which were published by SpringerLink, a reputable publisher mainly concerned with medicine and humanities. The author being an expert in bioethics meaning there is no reason to distrust this source. This book uses data from previous studies and surveys to gain enough varied information to make this book reputable. Boer had released another article in 1994. Ethical guidelines for the use of human embryonic or fetal tissue for experimental and clinical neurotransplantation and research (NECTAR). Journal of Neurology 242(1): 1–13 Boer GJ (1994). As at the time of writing reference 17 Boer was already an established author on bioethics and well established. As this is the case I do feel this book is useful and gives reliable information that I have used to enforce the points made earlier.
Bibliography
Web Based
[1] How common is Huntington’s Disease. Dennis H. Phillips, Ph.D. and first published in 1981. Republished in 20th April 2004
[2] Neural cell transplants may be potential therapy for Parkinson’s Disease. onMon,05/19/2008-08:07
[3] Glial Cell Line Derived Neurotrophic Factor Delays Photoreceptor Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa. Molecular Therapy (2001)
[4] Physiotherapy for Huntington's Disease. Manchester Neuro Physio, 2010.
[5]
[6] UHDRS. Huntington Study Group, 2010
[7] Huntington’s Disease. Joy B. Leffler, NASW, AMIA
[8] , King's College Hospital and Guy's King's ST. 2001
[9] What is Huntington’s disease? Arthur Schoenstadt, MD July 09 2008
[10] Huntington’s Disease, Bupa's Health Information Team, June 2010
[11]Huntington’s-disease-genetic-reference,-2008
[12] Survival rate statistics for surgical errors/complications, Patient Safety in American Hospitals, Health Grades 2004
Non-web based
[13] Effect of fetal neural transplants in patients with Huntington’s disease 6 years after surgery: a long-term follow-up study Published February 27th 2006
[14] Deep Brain Stimulation in Huntington’s Disease: The Current Status The Open Neurosurgery Journal, 2011, 4,7-10 2011
[15] Neural transplants in patients with Huntington’s
Disease undergo disease-like neuronal degeneration. F. Cicchetti
[16] Ethics of foetal brain cell transplant
BRITISH MEDICAL JOURNAL VOLUME 296 RAANAN GILLON 30 April 1988 pg 1212-1213
[17] Theoretical Medicine and Bioethics: , Ethical Issues in Neurografting of Human Embryonic Cells, pg 461-475,
[18]Neural Grafting: Repairing the Brain and Spinal Cord, October 1990
Images
[19] Punnett Square for Huntington’s disease
09/12/2009
[20] Pallidotomy probe
6/12/2011
[21] Clonazepam tablets
29/04/2007
[22] Physiotherapy
09/02/2010
[23] Pre-implantation genetic diagnosis diagram
10/03/2007
Standard physiotherapy for musculoskeletal problems.
Fig.1
Fig.2
H=faulty gene
h=normal gene
The child has a fifty per cent chance of having Huntington's (the red dots)
Electrical probe used in Pallidotomy to destroy brain lesions.
An outline of the steps of PIGD
Word Count:412
Word Count:847
Word Count:1206
Word Count:1549
Word Count:1960
Word Count:2247
Word Count:2612
by
alibongo73 (student)
