A potential MS vaccine?

Author: MS Research Australia.

To understand what the researchers have done, we need to take a step back and look at vaccines, mRNA and particularly the new class of vaccines, mRNA vaccines.

First some explainers:

mRNA

What is mRNA? mRNA is “messenger RNA” (messenger ribonucleic acid). RNA is a close relative of DNA (deoxyribonucleic acid). In human cells, and most other living organisms, all the genes are stored as DNA code. The DNA can be thought of as instructions for making protein. When a cell needs a new protein, it makes an mRNA copy from the DNA code which is locked up securely in the nucleus or centre of the cell. The mRNA is a short-lived message which then travels to out of the centre of the cell so the cell can use the mRNA as instructions or a template to make proteins and these proteins go and carry out all the functions that your body needs.

Vaccines

Vaccines are designed to introduce components derived from disease-causing organisms, or the organism itself, into the body to stimulate a response from the immune system. The immune system becomes trained to respond appropriately if it ever came across that disease-causing organism again, and hence we are protected against that disease-causing organism in the future.

mRNA vaccines

Traditional forms of vaccinations use a disabled form of an organism (called a live attenuated vaccine) or use proteins derived from the organism to inject into the body, which then generate a response from the immune system. We have now entered the mRNA vaccine era, with the Pfizer and Moderna COVID-19 vaccines being “mRNA vaccines”. The idea behind this strategy is rather than an injection of protein, the vaccine is an injection of a chemically modified form of mRNA directly into the body. The body’s cells then use these short-lived genetic instructions to make the Sars-CoV-2 protein (the virus that causes COVID-19) encoded within the mRNA. The immune system then sees this protein for the first time and mounts a response against it. This means there is an immune arsenal primed to respond quickly and effectively if the person becomes infected with the COVID-causing virus. Of note these COVID-19 vaccines are the first mRNA vaccines to be widely approved for use in humans.

How does this link to MS?

BioNTech, the German biotechnology company that developed one of the coronavirus vaccines in collaboration with the pharmaceutical company Pfizer, has recently published a scientific article in the prestigious scientific journal Science, looking at a non-inflammatory mRNA vaccine in animals with an MS-like disease, EAE (experimental autoimmune encephalomyelitis).

One key difference between this vaccination approach to traditional vaccine approaches and the COVID-19 mRNA vaccine approach is that for the MS-like disease, instead of trying to stimulate an immune response, it is trying to dampen down an immune response. MS is caused by an inappropriate immune response against the myelin located in the brain and spinal cord, so supressing this response is the aim of most treatments for MS. The dampening effect is based on some cutting-edge chemical modification of the RNA injected. Normally the body would think that it was foreign genetic material and raise the alarm, but without any alarm signal the body thinks it is part of itself and this tricks the immune system into thinking that the protein made from the mRNA isn’t foreign and it shouldn’t mount a response to it and switches off.

In EAE in animals, we know specifically which proteins found within the myelin the immune system attacks. Myelin is the fatty substance containing various proteins that cover nerve fibres in the brain and is damaged in people with MS, disrupting the signals between the brain and the body, leading to MS symptoms. However, in people with MS, while myelin does get damaged, no specific protein has been identified as a target for the immune system.

In this recent study the scientists injected mRNA encoding fragments of either the MOG protein or the PLP protein, both found in myelin and known to be targeted by the immune system in EAE. The animals then generated these protein fragments, with the hope that the immune cell would then realise that these are normal proteins in the body and stop attacking them. In the study, following the injection of mRNA (the “vaccination”), the scientists showed a decrease in the number of immune cells that recognised these myelin proteins as foreign and it appeared to prevent further deterioration in mice showing early symptoms of this MS-like disease.

Current medications for MS suppress the immune system as a whole, meaning that there is widespread suppression of immune responses, outside of the autoimmune response that leads to MS. In this study, the scientists also showed that the “vaccination” approach didn’t appear to hamper the body generating other immune responses and if the animals were exposed to other foreign proteins they could successfully fight them off. Interestingly, the introduction of specific mRNA seemed to have suppressed the immune system from generally attacking different proteins in myelin, suggesting it has a broader effect than first thought.

While this is an exciting research development, this is still in an early research phase. There are differences between human MS and EAE. In people with MS, we don’t know which components of the brain and spinal cord are targeted by the immune system. While this “vaccine” appeared to generally suppress the immune system attacking proteins in the myelin layer, we don’t know whether such an approach will work in people as no such immune targets have been identified in people with MS. This is something that only long and arduous research can reveal.

So while this is exciting research, and it has potential for application in many different autoimmune diseases, several hurdles need to be cleared before we are likely to see such strategies trialed in humans. In the case of MS, the search for the exact target of the immune system continues.

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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.