Tuesday, 24 September 2013

Research Update

This month there's been an update on various HSP related research activities posted on the Australian HSP Research Foundation website - http://www.hspersunite.org.au/. There are four articles on genetic testing and advances in testing ability, along with a study into leg muscle stretching and another on balance issues. Finally an article on the barrier that medication needs to cross is given. I've lifted the summaries of these pages and popped them here, along with links to the full articles.

Next Generation Sequencing diagnostics for HSPs - Germany leading in HSP gene testing
Researchers in Germany have developed an “HSP-Panel” that will provide HSPers with cutting-edge gene testing services. Based on next-generation sequencing (NGS), they have packed 38 HSP genes together with 50 other genes responsible for clinically similar diseases onto the panel. This means that almost all known HSP genes can be screened for in one single examination, in a much shorter time frame, and at around the same cost as the limited testing currently available.

HSP gene testing advance in China - Success in detecting point mutations

A gene chip has been developed in China that detects 96 of the more common HSP point mutations accurately and consistently in this gene screening.

Next generation gene testing - Helps identify non-SPG4 HSP

Associate Prof. and Director of Neurogenetics at Sydney’s Royal North Shore Hospital, Carolyn Sue, headed up this research study. Dr Sue has been involved with stem cell research for several years. Next Generation Sequencing (NGS) was used to successfully identify the HSP mutation in one quarter of HSPers in a study who were known not to have SPG4 HSP. Targeted NGS may be a useful method to screen for the multiple genes associated with HSP.  

Sharing genetics knowledge - New software will aid progress

The widespread availability of new software to analyse large genomic datasets will provide a fast, powerful and flexible tool to enhance identification of the genetic causes of diseases such as HSP.  A software tool (GEM.app) has been developed to annotate, manage, visualize, and analyze large genomic datasets (https://genomics.med.miami.edu/). GEM.app currently contains ~1,600 whole exomes from 50 different phenotypes studied by 40 principal investigators from 15 different countries.

Calf muscle spasticity studied - Lengthening the muscle may help 

Lengthening of the calf muscle by, for example, aggressive stretching programs may help to improve function in people with calf muscle spasticity.

Nerve conduction impairment in HSP studied - Signals to and from the brain are very different

The nerves that take signals from the brain to the legs and feet do so normally in HSPers, but different nerves that bring the signal to the brain from the feet are where the abnormal delay happens due to slow conduction times.

HSPersUnite gave a “plain English” interpretation of this research study from the Netherlands that examined posture and balance issues with HSP:
1. They put HSPers and non-HSPers on a platform that would tilt forwards or backwards under researcher control.
2. To maintain balance when the platform tips forward, it is necessary to contract the calf muscles to maintain balance; when it tips backward, you have to contract your shin muscles.
3. HSPers could not maintain balance as well, and had slower reaction times of the order of 30-40 milliseconds, compared to the non-HSPers.
The mechanism in operation is this:
* The feet detect a change in orientation of the surface with which they are in contact.
* Information is sent by an impulse along nerves to the brain where it is processed. The nerves that carry these impulses from the feet to the brain are called afferent nerves.
* A response is then sent by an impulse along different nerves down to various structures in the lower limbs such as muscles, which then respond so as to maintain balance. The nerves that carry these impulses down from the brain are called efferent nerves.
4. Next, the researchers introduced a sound into 25% of the trials to coincide with the start of the platform tipping backwards.
5. When there was a sound, both HSP and control groups responded faster, and they both responded in the same time.
The mechanism now in operation is this:
* The ear picks up the sound, which is transmitted to the brain for processing exactly the same for both HSPers and non-HSPers.
* This is faster and makes the (afferent) nerve response from the feet to the brain redundant as the brain already has the information it needs from the sound.
* A response is then sent by a nerve impulse along the efferent nerves down to the lower limbs.
So it is reasonable to conclude that the efferent nerves that take signals from the brain to the lower limbs do so normally in HSPers, and that the afferent nerves bringing the signal to the brain from the feet (when there is no sound) are where the abnormal delay happens due to slow conduction times.

The blood-brain barrier

The blood-brain barrier is important in HSP because any drug treatment needs to successfully cross this barrier to find its way into the upper motor neurons or nerve cells to counteract the impairment caused there by HSP mutations. An article, written by Dr Karl (a funny, slightly eccentric, wildly enthusiastic and hugely knowledgeable, self-professed geek who regularly shares his wisdom on all manner of scientific things on radio, TV and in print) explains what the blood-brain barrier is and how it works.

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