Wednesday, 30 October 2013

Dysautonomia Research Down Under - Baker IDI Human Neurotransmitters Laboratory. Dysautonomia Awareness Month

As Dysautonomia Awareness Month starts to wind up for another year I thought it'd be great to have a short look at some of the research that is under way here in Australia. The Baker IDI Heart and Diabetes Institute, here in Melbourne, Australia, is conducting research in a number of areas from drug trials to understanding the underlying mechanisms of various autonomic disorders. Thanks to the staff from the Human Neurotransmitters Laboratory


Researchers at the BakerIDI Human Neurotransmitters Laboratory are actively involved in investigating disorders associated with abnormalities of the sympathetic nervous system resulting in orthostatic intolerance. Their research covers both disorders associated with Autonomic Failure and the Dysautonomias. This group receives funding via The Greg Page Fund for Orthostatic Intolerance.

Recent research from the group, headed by Professor Murray Esler and Professor Gavin Lambert, has contributed significantly to our understanding of these conditions.

POTS (Postural Orthostatic Tachycardia Syndrome) and Noradrenaline transport.

Dr Richard Bayles as part of his PHD investigated patients with POTS. He found that POTS patients have lower levels of the Noradrenaline transporter –the protein that inactivates the noradrenaline signal. He then went on to see if this was due to a genetic change – this wasn’t the case, the genes were normal. What he found was a change in the proteins that chromosomes are wrapped around that effectively turned off the gene the codes for the noradrenaline transporter in patients with POTS. So the gene is normal but it has been turned off. This insight will guide further research into the biology of POTS and the development of future therapies.


Bayles R et al (Arterioscler Thromb Vasc Biol. 2012;32:1910-1916.)

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Work conducted by Dr Gautam Vaddadi demonstrated impaired tightening of blood vessels in response to upright posture in patients with vasovagal syncope, with different findings in patients with low BP at rest and those with a normal BP. This understanding has lead the group to undertake a trial of the Noradrenaline prodrug L-DOPS in patients with vasovagal syncope. I have linked to the study below throughout this month. Here are some more details for those here in Australia who may be interested in participating.


Clinical and Neural Effects of L-DOPS on Low- and Normal- Supine Blood Pressure Variants of Orthostatic Intolerance.


We are looking for participants aged 18-50 who suffer from recurrent fainting or near fainting spells due to Vasovagal Syncope to participate in a trial investigating the benefit of a new medication - L-DOPS - in this condition. Participants will have either low or normal lying blood pressures. Participants will have had symptoms occurring at least weekly for ≥ 6 months. Symptoms include lightheadedness, weakness, blurred vision, fainting or near fainting.

Study details

The Human Neurotransmitters laboratory at Baker IDI has commenced a new study looking at the effect of a drug called L-DOPS in patients with Vasovagal syncope in association with either low or normal lying blood pressure. The study involves detailed examination of sympathetic nervous system function on two occasions in addition to clinical evaluations. The sympathetic nervous system, the stimulant arm of the nervous system is responsible for our "flight and fight" response to a threatening situation. The sympathetic nervous system is also crucial in the control of blood pressure and allows us to stand upright and supply blood to our vital organs, including the brain, in the face of gravity that pulls blood towards our legs. L-DOPS is a nerve transmitter precursor that is converted by the body to noradrenaline, the main nerve messenger of the sympathetic nervous system. We are studying whether increasing noradenaline by the use of L-DOPs improves physiological responses and symptoms in patients with these forms of orthostatic intolerance.

Eligibility

To be eligible for this study, you must:
  • be aged 18-50
  • have a disorder of Orthostatic Intolerance consistent with Vasovagal Syncope with either low or normal lying blood pressure
  • have had other conditions that could cause these symptoms excluded
  • be able to withhold medications that affect blood pressure for the duration of the study
  • be prepared to use appropriate contraception for the duration of the study
  • not be pregnant or breastfeeding
  • not be taking antidepressant medications
  • have no history of hypertension, heart disease, diabetes 
Patients with the Postural Orthostatic Tachycardia Syndrome (POTS) CANNOT be enrolled in this study.

What happens in the study?

During the study you will have two detailed assessments of your sympathetic nervous system, one at the beginning of the study and one at the end. These assessments take 4 hours each and involve invasive procedures such as the recording of nerve signals and the placement of a small tube in an artery and a vein in your arm.

Following an open label tolerability phase, the study will involve the blinded administration of the trial drug or placebo for 28 days each with clinical assessments at the end of each period. Further open label administration of L-DOPS is undertaken prior to the final assessment.
The total study duration is 4 months.

All study visits are performed at The Alfred Hospital, Commercial Rd , Melbourne.
Participants will be reimbursed for parking costs.

Interested?

If you would like to participate, or would like to know how you can help, please email us at fainting.study@bakeridi.edu.au
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For those unfamiliar, a short explanation of Dysautonomia can be found here.
One of the most famous people with a form of Dysautonomia is former Yellow Wiggle, Greg Page, who lent his name to a research fund at The Baker IDI, here in Melbourne, Australia. Donations can be made at The Greg Page fund For Orthostatic Intolerance.
And because many of us hope this research leads to us all feeling better, I give you Nina Simone's version of Feeling Good.

5 comments:

  1. I'm studying genetic switches that turn genes on and off RIGHT NOW in class so I felt like jumping up and down when I read this and understood it!

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  2. Wish they were doing this study in the UK!

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    1. I'm pretty sure STARS.org.uk are involved in research Tricia. Have you linked up with them. Otherwise UKPOTSies should be able to let you know about local research. It's always a good feeling to know someone in your country is caring enough to do research in the area. :)

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  3. Thanks for the share Bob. I wonder if they will be running periodical ANS tests to see if their various levels are improving. Not to mention the use of an ans test would cut down on the number of invasive procedures required.

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All who are lovely enough to comment should be showered with cup cakes, glitter and macarons. I promise to use my spoon bending mind powers to try and get that happening for all who are lovely enough to share their words. Those who go the extra step to share posts should really get a free unicorn. Or at least the gift of finding the shortest and quickest line at the supermarket on a regular basis. xx