Mystery Missing Antibodies

One of the perennial questions of MS research is, what is it that triggers the attack on the nervous system in the first place? We have plenty of information about some of the genetic and environmental factors that can increase a person’s risk of developing MS (see our recent article here). But exactly what the first biological trigger is that causes the immune system to attack the nervous system remains a mystery.

We know that the ongoing damage to the myelin sheath that protects nerve fibres is driven by autoimmune processes, where a person’s immune system turns on their own body. However, in the majority of autoimmune diseases, scientists have been able to identify antibodies in the bloodstream that are specific to that disease and inappropriately attack the tissues affected in those diseases. Antibodies are normally produced by the immune system to respond to invading micro-organisms, such as bacteria and viruses. In autoimmune diseases, antibodies are produced that mistakenly recognise a part of the human body instead.

Many studies seeking to identify the antibodies that might trigger MS, conducted over many years, have produced conflicting results. Some researchers have found antibodies that appear to specifically target the central nervous system, but others have been unable to confirm these findings.

Two Australian researchers who have been diligently pursuing this line of research are Dr John Parratt and Professor John Prineas of the Brain and Mind Centre at the University of Sydney. Dr Parratt was the recipient of the MS Research Australia Neil and Norma Hill Clinical Research Fellowship from 2010 to 2013.

Dr Parratt and Professor Prineas, have recently published their findings from this study in the Multiple Sclerosis Journal. In this study, they conducted a detailed ‘survey’ of the antibodies present in the blood of people with MS.

They collected blood samples from 106 people with MS, 156 people with other neurological diseases and 70 people with no neurological disease. They then screened these samples for brain-specific antibodies, using a technique in which the samples are washed over slices of brain tissue. The tissue is then examined under the microscope to see if any antibodies have stuck to the brain cells.

The researchers found a whole range of antibodies in the samples that bound to the brain tissue. Some had never been detected before in other studies and appeared to very specifically ‘stick’ to certain types of brain cells. This is an exciting finding in itself, which the researchers attribute to the novel technique they used to process the brain tissue. They will be investigating these antibodies in more detail.

However, despite these antibodies being quite common in the blood of people with MS, disappointingly, none of the antibodies seemed to be unique to people with MS. They were also found in healthy individuals and those with other neurological diseases, suggesting they may not be specifically causing MS.

The authors discuss a range of studies over the years that have examined brain tissue from people with MS for the presence of antibodies and immune cells in the earliest stages of MS lesions. Again the results have been conflicting and hotly debated. Several studies, including a pivotal study conducted by Professor Prineas and colleagues more than 10 years ago, suggested that the very earliest signs of myelin damage were not associated with immune cells or antibodies.

And so the results of Dr Parratt’s and Professor Prineas’ current study, and several of those that have preceded it beg the question: If it is not a myelin-specific antibody that triggers myelin damage in MS, then what is it?

Is it a problem in the myelin-producing cells themselves that causes them to begin dying? This could then trigger the immune and support cells in the brain to respond to clean up the damage and that in turn triggers a bigger immune response. Or is it a flaw in the immune system (which some of the genetic studies suggest) that allows the immune cells to become ‘trigger happy’ and set off an inflammatory response in the brain with minimal or no provocation?

The mystery continues. But what is certain is that the work done by Dr Parratt and Professor Prineas helps us to rule out some possibilities and allows us to keep moving down other lines of investigation to bring us closer to solving the mystery.

Article courtesy of MS Research Australia www.msra.org.au

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Andrew Cushen

Trustee

Andrew is an independent corporate affairs and strategy consultant, working and living in Auckland. He has previously held senior positions in a number of corporate and not-for-profit entities in New Zealand.

Across his career, Andrew has worked as a funder of research projects (albeit in different areas than medicine and health), served in a number of not-for-profit governance roles, and been successful in developing and implementing collaborative funding models to extend investment in research and community programmes.

Andrew’s interest in Multiple Sclerosis stems from his father’s diagnosis with progressive MS in the early 2000s, and he is keenly interested in research, treatment and management approaches that may lessen the impact of MS on those diagnosed and their families.

Julia Howell

Trustee

Julia is a qualified nurse and midwife, with a varied career including specialising in eating disorders, primary healthcare, and management.    

Julia, in partnership with a GP, set up an outpatient clinical trials unit (Southern Clinical Trials). Under her leadership this grew into a network of 6 sites across NZ. This network merged with another one in 2021 to form PCRN, NZ’s largest clinical trials network. Julia is currently working as joint COO for PCRN.

Julia’s daughter was diagnosed with MS aged 14 and she has been intimately involved with her management over the years.

 

Jan Campbell

Trustee

Born in Ōtautahi Jan trained as a nurse in Christchurch, as a midwife in Winchester, UK and has a degree in philosophy with particular interest in healthcare and business ethics.

After working in the public health system in the UK and NZ, Jan joined Roche Pharmaceuticals based in Auckland in 1999. As a respected senior leader and Medical Director, she established a medical division over the ensuing 20 years responsible for significant investment in clinical trials in NZ, developing a top-class global medicine information service, compassionate medicine supply for kiwis in need, pharmacovigilance oversight and a team working closely with patients, specialists, MEDSAFE and PHARMAC to support the safe and appropriate use of Roche medicines.

As a retiree Jan has volunteered for Mercy Hospice in Auckland and the WBoP Museum in Katikati. Now living in Ōtepoti, Jan sits on both the MS Research Trust and MSNZ executive committees with a keen interest to ensure people with MS get a fair go in NZ.

Dr Elza Cloete

Trustee

Elza is a Neonatal Paediatrician at Christchurch Women’s Hospital. Originally from South Africa, she moved to New Zealand in 2006 and completed her specialist training in Auckland.

Subsequent to that she embarked on doctoral studies at the University of Auckland’s Liggins Institute and obtained a PhD investigating congenital heart disease in new-born babies.

Elza received the Vice-Chancellor’s award for best doctoral thesis for her research and is the author of several research publications. She moved to Christchurch in 2020 for a work opportunity in clinical practice.

Elza was diagnosed with MS in 2012 and brings a consumer perspective and research experience to the Trust.

Dr Ernie Willoughby

Trustee

Dr Willoughby has been a consultant neurologist at Auckland City Hospital (1979 to 2021 – now retired, emeritus) and clinical associate professor at Auckland University School of Medicine.

He directed the MS clinic at Auckland Hospital, has had a long association with the Auckland and NZ MS Societies, and is a member of the International Medical and Scientific Board of the MS International Federation.

Dr Brian Linehan

Independent Trustee

Dr Brian Linehan is a retired pathologist who was previously Managing Director of Medlab Hamilton.

He is currently Chairman of the Tranmere group of investment companies and a Director of a number of other private companies. In 2014, he retired after 12 years on the Council of the University of Waikato where he was Pro-Chancellor.

He is a past Chairman of the New Zealand Medical Association, past Chairman of NZMA Ethics Committee, past President and Chairman of CMAAO (Combined Medical Associations of Asia and Oceania) and past Chairman of IANZ (International Accreditation NZ).

Brian was diagnosed with MS in 2007 but is still active and mobile.

Peter Wood - JP, BCom, AGNZ, ACIS, FNZTA

Treasurer

Peter gained his commerce degree at Victoria University of Wellington and has been practising as a Chartered Accountant initially in Wellington and then in Tauranga.

Peter was a respected and trusted advisor to many businesspeople.
He is now resident in Auckland and consultants to a limited number business clients.

He has also served his community through involvement with Jaycees, Lions and Rotary clubs and a number of charitable trusts.

Peter is currently the Treasurer of Multiple Sclerosis Auckland and a trustee of the Multiple Sclerosis Auckland Trust. Peter is a Justice of the Peace and a member Governance New Zealand and is a Fellow of the NZ Trustees’ Association.

Neil Woodhams

Trustee

Neil is an independent health management consultant who has had an extensive career in health management as a senior manager or consultant to government, DHBs, primary care and community providers. 

Neil is President of MS New Zealand and a trustee of the MS Auckland Region Trust. Neil was also President of MS Auckland until he stepped down from this role mid-2020 to concentrate on his national roles.

Neil’s wife was diagnosed with MS in 1994. One of his four sons was also diagnosed in 2010.

Neil strongly believes in the objectives of the NZ Multiple Sclerosis Research Trust and has advocated for the establishment of the Trust for over 10 years.

Sir William Gallagher

Trustee

Sir William is renowned as a motivational, pragmatic and hands-on businessman in and outside of New Zealand and has a reputation both as a dynamic leader and one of NZ’s most astute businessmen.

Still very involved in the daily operation, he maintains regular contact with customers in the 130 countries in which Gallagher products are sold spending up to 150 days a year on the road representing the company and its philosophies and emphasising the ethics and integrity of his professional and personal dealings.

His achievements have been officially recognised by a string of awards, the latest to mark his commitment to enterprise and leadership skills being his Knighthood in the 2010 New Year’s Honours List. He was also the 1996 winner of the prestigious Excellence in Communication Leadership award, the first time in its history that it had been awarded outside of North America. He also received an MBE in 1987 followed by a Companion of the New Zealand Order of Merit (CNZM) in 1998.

Sir William Gallagher - KNZM, MBE. HonD

Patron

Sir William is renowned as a motivational, pragmatic and hands-on businessman in and outside of New Zealand and has a reputation both as a dynamic leader and one of NZ’s most astute businessmen.

Still very involved in the daily operation, he maintains regular contact with customers in the 130 countries in which Gallagher products are sold spending up to 150 days a year on the road representing the company and its philosophies and emphasising the ethics and integrity of his professional and personal dealings.

His achievements have been officially recognised by a string of awards, the latest to mark his commitment to enterprise and leadership skills being his Knighthood in the 2010 New Year’s Honours List. He was also the 1996 winner of the prestigious Excellence in Communication Leadership award, the first time in its history that it had been awarded outside of North America. He also received an MBE in 1987 followed by a Companion of the New Zealand Order of Merit (CNZM) in 1998.