Researchers into dystonia come from many specialty areas – neurology, pure science, biology, chemistry, genetics, psychology. Clinical studies are meticulously planned, and then application is made for a funding grant to do the study.
Often, very well planned applications do not get accepted though. Many areas of medicine besides dystonia also want funding and dystonia has historically not been prioritized.
When a grant is awarded, the study proceeds with clinical trials, analysis and reports. Then peer review is sought by scientists and physicians before the study is published in scientific journals and is available in medical libraries. It is a long process but that is how the ultimate answer to dystonia will be found.
2023- The timeline of this website shows developments about genetic links to dystonia and about MRI evidence of dystonia in very recent years.
There is also a very new development in 2023.
Saliva and dystonia
Researchers have been working on some fascinating theories lately, related to human saliva.
- Saliva can be used to test for genetics.
- Saliva can also indicate what illnesses a person has or what the body is doing that shows it is fighting an illness.
This work to date has not yet been explored much about dystonia. However it is being explored successfully for a related movement disorder, Parkinson’s Disease.
In 2023 as we look at progress in that area, there seems potential to one day have a way:
– to test for dystonia using a saliva sample, which would be inexpensive, quick and done easily in a doctor’s office
-to look at the genetics of a given patient and determine what treatments and medications might be most effective for them and what treatments should not be used.
These two developments have NOT yet happened for dystonia.
However looking at the research is interesting.
SALIVA TESTING AND GENETIC SEQUENCING
Saliva contains body cells of that person. The white blood cells and buccal epithelial cells have been found to be rich sources of genomic DNA, in some cases as useful as are blood samples for such collection, and at much lower cost. Saliva retains its integrity at room temperature much longer than does blood so is easier to store and study.
In 2012 Dr. Cory McLean from 23andMe, published a research paper looking at the whole genome sequencing of 50 individuals, 37 known to have Parkinson’s Disease and 13 without it. It was found that in Parkinson’s there are over 20 single nucleotide elements different from the general population and a few of these variants in particular could be used to help identify Parkinson’s disease generally.
Dr. C. A. Samson in 2020 however found that doing a genome sequencing of humans by using saliva has some technical challenges not found with samples from blood. What a person has eaten recently has traces in the saliva and if it was vegetable, wheat, meat or fish that item also had DNA. It is a problem to try to filter out and not confuse that DNA with the human DNA. In addition, studies from DNA Genotek and 23andMe found that about 10% of what is in saliva is bacteria. Bacteria also has DNA and it was important to figure out how to filter out that DNA and not confuse it with the DNA of the person.
This research however has been done and strategies have been developed to filter out and not confuse those elements. Restricting what the person recently ate seems to be one strategy, and another was to do an DNA sequence of 84 types of common bacteria themselves and then eliminate those from the study of human DNA. Trying to sequence the DNA of animals and plants that might be interfering is apparently too huge a database but sequencing 7 common ones has been done.
Researchers have been able to do genetic sequencing then of humans with very high accuracy about the ancestry of that person.
What difference could that make for those of us with dystonia?
A genetic link has already been found to some forms of dystonia. Several research studies have identified genes that are markers for it. Not all with the gene variant get dystonia and not all who have dystonia have that gene variant – but some do and in high enough proportions that the gene variant is considered linked to dystonia ( see the chronology and timeline section of this website)
It is also known that medication affects people differently but why is not always understood. However our surveys found and anecdotally people often report a familial pattern of response to some pills. If that turns out to be the case, then a genetic sequencing could be very useful to help doctors know what pills not to give this patient and what pills seem more likely to not have adverse side effects.
With dystonia in particular, there are cases of dyskinesia and drug-induced dystonia, where researchers found that the dystonia appeared only after taking a certain medication. To avoid medication that may create risk for developing dystonia is a very advisable goal.
SALIVA TESTING AND ILLNESS
There is to date no saliva test for dystonia.
However- there is now one for Parkinson’s disease as of June 2023.
Parkinson’s disease is a neurogenerative condition which affects the area of the brain governing movement. It is incurable, usually progressive and affects 10 million people worldwide. It also is difficult to diagnose in the early stages. Doctors can study muscle movement and tremor, and may notice loss of smell or sleep disturbance that patients report but it often takes years as the condition worsens, to determine what is going on. Medical imaging such as SPECT scan, MRI, PET Scan and dopamine level scan or DAT scan also have been found useful but they also are very expensive.
This means that this common and debilitating progressive condition is experienced for years without clear diagnosis. In that interval there is suffering to the patient, often high cost to the patient and often high cost to the medical system trying to get to diagnosis. Though the condition is not curable it is often treatable, and earlier detection has the potential to lessen suffering and lessen cost both. There are some medications that are known to be highly effective to treat Parkinson’s and slow its progress.
When doctors test for disease they often find evidence of it in the urine or blood. They can detect some viruses, bacteria and certain proteins and enzymes only produced in response to a given illness. These indicators then are medical signs of an illness in the body. They are called biological markers or biomarkers. It is costly and sometimes difficult or embarrassing to collect blood or urine samples however and scientists have wondered if there are such biomarkers in saliva. Saliva is easy to access and testing for it by a drop is non invasive.
It turns out that many illnesses do show up in saliva, including viruses. Research is looking at indicators for measles, mumps, rubella, hepatitis A, B and C. Other chemicals in the saliva have been found to increase in number in cases of tooth decay, periodontal disease, even lung, breast, prostate or oral cancer. There are sometimes changes in the DNA, RNA and proteins in the saliva which are signs of the body fighting specific illnesses. As such biomarker testing has become a new interest of science. It is even being used to examine whether the body is fighting certain heart conditions.
Saliva has many uses. It cleans the mouth, kills bacteria and is part of the immune system, washes way food, helps the first stage of digestion of starches. It is already adding chemicals to process what enters the body and it indicates the health of the body that is being entered
In 2023 Dr. Maria De Rosa and Dr. Matthew Holahan in the faculty of science at the Carleton University in Ottawa have been working with such biomarkers. De Rosa and Holahan have been studying Parkinson’s disease to use a synthetic DNA molecule called an aptamer to block the progression of the illness.
It occurred to researchers to look at biomarkers for Parkinson’s and to see if they can be found not just in blood or other tissue but in saliva. Dr. Ravi Prakash is a Carleton university electrical and biomedical engineer who had an idea to develop a saliva test that could detect such early signs of Parkinson’s. He was able to collaborate with De Rosa and Holahan to identify presence of the known biomarkers for Parkinson’s. The device to test saliva samples is accessible, can be made with a 3D printer and makes a circuit board with disposable single use sensors and is portable. In this way patients could get an easy test at the regular doctor’s office through a cheek swab or drool sample, dropped onto to the sensor. The device then plugged into a USB port of a computer would give results quickly.
Comment:
Clearly this a complicated area of study and we are living at a time of it developing. We don’t have answers yet fully but it is exciting to watch research in this area.
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In other news about research
The surveys on this website tried to assist in the early stages of that process – the information gathering, ideas generating start.
There are many researchers interested in dystonia. It must be exciting and frustrating to try to understand this unusual condition. They hold national and international seminars sharing ideas and motivating each other to keep working to cure the so-far incurable. I like the conference theme topics of “Muscles behaving badly” or “Love your neuron.” These are great people and I want to help them succeed.
Meanwhile here is a list of 2020 clinical studies about dystonia I have found online, sorted by whether researchers are currently recruiting patient input. For further information see clinicaltrials.org.
If any researchers would like to mention their current studies on this list, please contact bevgsmith@gmail.com.
(June 2020)
Recruiting
- Exercise training in dystonia
- Incobotulinum toxin A for focal task specific dystonia of musician’s hand
- Effect of increasing motorcortex inhibition on task specific dystonia
- Neuromuscular electrical stimulation for jaw-closing dystonia
- Registry of Deep Brain Stimulation with the Vercise TM System
- Incobotulinumtoxin to treat focal hand dystonia
- Long term safety of repeat treatments of Daxibotulinumtoxin A – cervical dystonia
- Targeting methods of botulinum toxin injections for cervical dystonia
- Abobotulinum toxin and neubotulinum toxin- cervical dystonia
- Assessment of brain activities in cervical dystonia
- Clinical and kinematic assessment- Botox R injection parameters – cervical dystonia
- Deep Brain Stimulation surgery for focal hand dystonia
- TMS and Botulinum toxin in primary cervical dystonia
- Transcranial electrical stimulation for cervical dystonia
- Motor network in Parkinson’s disease and dystonia- mechanisms of therapy
- Pathophysiology of dystonia and complex regional pain syndrome
- Propensity to develop plasticity in the parieto-motor networks
- Dystonia Genotype-phenotype correlation
- Cholinergic Recept imaging
- Osteopathic Manual treatment Parkinson’s Disease and Truncal Dystonia
- Two guidance techniques for botulinum toxin injections- focal dystonia
- Repetitive transcranial magnetic stimulation for Dystonia and Tremor
- Deep Brain Stimulation- WILSTIM – DBS
- Analysis of Gait before and after botulinum toxin treatment -focal dystonia
- Finger individuation training – writer’s cramp
- Effect of the visual information change in functional dystonia
- Validation of the zigzag tracking task test – handwriting and writer’s cramp
- Clinical outcomes for deep brain stimulation
- Deep brain stimulation – retrospective outcomes study
- Clinical and psychological studies of tremor syndromes
- Effectiveness and reliability of hypnosis in sterotaxy
- Deep brain stimulation surgery for movement disorders
- Movement disorders and early maladaptive schemas
- Sensory gaiting measured with microelectrode recording during DBS
- Spine MRI in patients with deep brain stimulation
- Database of clinical data for patients with variants in IRF2BPL gene
- MRI study of infinity DBS system
- Physiological brain atlas development
- Abbott DBS registry of outcomes for indications over time
- Using wearable and mobile data to diagnose and monitor movement disorders
- Genetic characterization of movement disorders
- Laryngeal vibration for spasmodic dysphonia
- Sodium oxybate in spasmodic dysphonia and voice tremor
- Imaging genetics of spasmodic dysphonia
Not yet recruiting
- Tele-yoga and dystonia
- Interactions between striatum and cerebellum in ADCY5 and PRRT2 dystonias
- Trial of non-invasive stimulation in cervical dystonia
- Open-label study to define safety, tolerability of Deutetrabenzaine (Austedo)
- Conversion to Dysport in Cervical dystonia patients
- Clinical trial to compare Botux R verus Botox R – cervical dystonia
- Botulinum toxin Type A for focal Dystonia associated with pain in Parkinson’s Disease
- Imaging neuromelanin and iron in Dystonia/ Parkinsonism
- Using DBS to probe basal ganglia dysfunction
- Cortical basal ganglia speech networks
- Physiology, imaging and modeling of essential tremor
- Quantifying muscle tone in patients with brain injury
- Stereotactic frame system for neurosurgery
- Brain network activation in patients with movement disorders
Lived Experience With Dystonia 