Research into Neurology: Bedside to Lab and Back Again — Nick Verber — 2nd Nov 2020

Nick Verber is a research regis­trar work­ing for his PhD at the Sheffield Institute for Translational Neuroscience Institute (SITraN), University of Sheffield. He gave an excel­lent talk, very suc­cess­fully over­com­ing the tempta­tion of many medics to litter their lec­tures with clin­ical jargon. It was clearly delivered and easily fol­lowed by a large Zoom gath­er­ing of 44 Probus mem­bers.

Although there is a long way to go before there is a cure for motor neuron dis­ease (MND), the Institute here in Sheffield, led by Dame Prof Pamela Shaw, is a world leader in clin­ical and sci­entific research into this and other chal­len­ging and dis­tress­ing con­di­tions.

Nick began with a typ­ical case his­tory which illus­trated the pro­gress­ive nature of MND over a two year period, although there is a great deal of vari­ation in the rate of pro­gres­sion from patient to patient. MND is cruel to patients, rel­at­ives and their friends. It affects all vol­un­tary muscles through­out the body and the case his­tory illus­trated how it pro­gressed from minor weak­ness of the limbs to slurred speech, dif­fi­culty in swal­low­ing which can result in saliva, food and drink going down into the lungs, and breath­ing prob­lems.

Cause of MND

This is com­plic­ated and not fully under­stood. The vast number of nerves con­trolling vol­un­tary muscles become dam­aged and cease to func­tion prop­erly (in con­trast to sens­ory nerves bring­ing sig­nals to the brain about touch, smell, sight, pain etc. and to auto­nomic nerves which con­trol the gut, bowels, water­works and sexual func­tion, all of which remain unaf­fected in MND).

Dr Weaver’s amaz­ing dis­sec­tion — for details see last para­graph

These motor nerves carry sig­nals from the brain to muscles involved with move­ment, pos­ture, speech, swal­low­ing, laugh­ing, and coordin­a­tion of eye move­ments. Eye and facial move­ments are affected much later. Poor strength in the head and neck leads to deformed pos­ture, as seen in the famil­iar wheel­chair pos­ture of Stephen Hawking.

Stephen Hawking. Note the effect of wast­ing of head and neck muscles and fail­ure to sup­port the head

As muscles pro­gress­ively weaken, mental fac­ulties usu­ally remain uncom­prom­ised, caus­ing immense dis­tress and frus­tra­tion. But patients are often prag­matic and pos­it­ive, and are keen to par­ti­cip­ate in, and raise funds for, research.

Prevalence

MND is rel­at­ively rare, with 5000 people having the con­di­tion in the UK. It has the same life­time risk as the more common mul­tiple scler­osis (MS), but there are sub­stan­tially fewer people with MND due to the poor life expect­ancy.

Treatment

Successful treat­ment is indi­vidu­al­ised and patient focussed, led by a team of spe­cial­ists, nurses, physio­ther­ap­ists, dieti­cians etc. who make the dia­gnosis by clin­ical exam­in­a­tion and invest­ig­a­tion with blood tests, brain MRI, lumbar punc­ture. Treatment centres around indi­vidu­al­ised mul­tidiscip­lin­ary care with pro­vi­sion of social, psy­cho­lo­gical and diet­ary sup­port.

Medication has lim­ited use­ful­ness but Riluzole may slow nerve deteri­or­a­tion. Other inter­ven­tions include diet­ary sup­ple­ments, homo­gen­ised food, gast­rostomy (feed­ing tube inser­ted through the abdom­inal wall into the stom­ach), physio­ther­apy, splints, highly soph­ist­ic­ated wheel­chairs, assisted vent­il­a­tion, occu­pa­tional ther­apy, mobil­ity and cut­lery aids.

Mobility and Cutlery aids

Speech and lan­guage ther­apy is import­ant, and voice bank­ing is avail­able. The inab­il­ity to swal­low saliva (nor­mally 500ml per day) and drool­ing is dis­tress­ing and helped by simple med­ic­a­tion. Approximation of voice with regional accents has recently become pos­sible, over­com­ing to some extent the imper­sonal Dalek sound of the com­puter. Communication prob­lems as speech and motor func­tion decline can be addressed by eye sig­nals facil­it­at­ing com­puter typing.

The main aim of treat­ment and long-term mon­it­or­ing is to allow the patient to retain inde­pend­ence and qual­ity of life.

Research

Nick touched on how MND research is con­duc­ted, using bio­mark­ers

Biomarker research

to assess change in patient con­di­tion, with the aim of provid­ing evid­ence to guide appro­pri­ate treat­ment. Blood tests, nerve con­duc­tion stud­ies, MRI and con­stant mon­it­or­ing of dis­ease are all part of this pro­cess, and are par­tic­u­larly import­ant for assess­ing pro­gress during clin­ical trials

Research is expens­ive. Identifying a useful bio­marker is cru­cial for attract­ing research fund­ing. Charitable fund­ing is helped by high pro­file patients such as Doddy Weir and Rob Burrows who make a pos­it­ive con­tri­bu­tion towards dis­ease treat­ment through research.

MND com­prises sub­groups of patients with sim­ilar but dis­tinct dis­ease pro­files. One research aim in Sheffield is to improve defin­i­tion of these sub­groups in order to improve their treat­ment and avoid any inter­ven­tion found not to work. Some bio­mark­ers differ between MND patients, or between patients and healthy volun­teers.

Skin biopsies are simple, quick, pain­less (fol­low­ing local anaes­thetic admin­is­tra­tion) and read­ily access­ible (with patient con­sent). Fibroblasts are present within them. These are imma­ture cells with mat­ur­a­tion poten­tial to develop new skin or scar tissue (in the case of trauma). Another research strategy in Sheffield is to give genetic inform­a­tion to these fibro­blasts to con­vert them to nerve tissue in a labor­at­ory set­ting. This over­comes a major prob­lem in neur­o­lo­gical research of being unable to access live brain or nerve tissue for exper­i­ment­a­tion.

Nick con­cluded by giving his grat­it­ude to the patients and volun­teers that have donated their time and samples to his research.

If anyone has any interest in volun­teer­ing for research, then please get in touch via his email address at the bottom.

Figures

Couldn’t resist this one! Dr Weaver’s amaz­ing dis­sec­tion of Harriet Cole’s nervous system (its huge com­plex­ity is illus­trated by the fact it took from 1888 to 1893 to com­plete the dis­sec­tion, which can still be seen in Philadelphia) (Barton M. The Nervous System of Harriet Cole. Past Medical History. Aug 18, 2018)

Correspondence address:

n.verber@sheffield.ac.uk

Those of you who were impressed by the work that Nick and his col­leagues are research­ing can make a dif­fer­ence by donat­ing by copy­ing and paste this into your search engine.

http://sitran.org/support-us/