What are the latest breakthroughs in multiple sclerosis (MS)?

The potential of neuroprotective agents for a whole new form of treatment.

The MS International Federation states that the disease is ‘one of the world’s most common neurological disorders. In many countries, it is the leading cause of non-traumatic disability in young adults. While some people with MS experience little disability during their lifetime, as many as 60% may be unable to walk without assistance 20 years after onset.’ This means that new research into MS is a high priority.

Current treatments for MS

MS, multiple sclerosis, is the most frequent chronic inflammatory disease of the central nervous system . Several different types of MS exist and among those the relapsing-remitting form leads to disability during the relapses followed by complete and partial remission in the remitting phase. The severity of relapses and the general condition of the patient gets worse as the disease progresses. Current treatments for MS are primarily anti-inflammatory therapies which work by modulating the immune system and thereby inhibiting the causes of the diseases. However, these medications only have a limited effect on slowing down disability progression¹.

What is neuroprotection?

Multiple sclerosis causes inflammation of tissue which releases chemicals that destroys nerve fibres, causing the disabilities commonly seen with disease. Neuroprotection is proposed as a way to protect these nerve cells from damage and thus protect the central nervous system and stop or reduce the symptoms and disabilities².

The Handbook of Neuroprotection - K.K. Jain, 2011 - by Springer lists approximately 80 categories and includes examples of over 400 known neuroprotective agents. These include quite common substances from vitamins to opioids and their neuroprotective effects have been identified from experiments and clinical trials. However, to develop the right treatment or combination of substances researchers first need to map the unique characteristics of MS and how it affects patients.

Late last year the first major steps in understanding the unique neurodegenerative effects of the disease have been made. In new research from UCLA – The University of California – published last week, a team of researchers made a significant breakthrough in identifying specific gene expressions that could explain why neuronal damage is not repaired in MS. ‘Altered cholesterol synthesis gene expression in astrocytes in spinal cord and optic nerve was identified as a potential target for walking and visual disabilities, respectively.’³.

Core to the research was a theory based on the idea that since the type and severity of disabilities can differ significantly, that the molecular mechanisms creating each disability might also differ. In fact MS is multifocal in its symptoms² – meaning, it affects different parts of the nervous system in different ways. To this end, the research group looked at astrocytes, a brain cell that is activated in people with MS and plays important roles in the disease. Their results in mice with MS supported their hypothesis that targeting the specific gene expressions in the central nervous system (brain and spinal cord) can have a neuroprotective effect and result in a reversion of disability.

Using mice, the team looked for astrocytes in different parts of the brain and spinal cord that are linked to walking, vision and cognition. Then they compared gene changes among the regions that correspond to different disabilities. In particular, when looking at the spinal cord, which is essential for walking, they found lower cholesterol synthesis in the mice with MS. Cholesterol is made in astrocytes and helps make myelin.

"The scientists hypothesized that while inflammation causes loss of myelin, it is the decrease in cholesterol synthesis gene expression in astrocytes that explains why myelin loss and nerve damage aren’t repaired in MS. When the scientists treated the mice with a drug that increased expression in cholesterol synthesis genes, the mice’s ability to walk improved significantly."³

What is the impact of this result?

Though a human treatment may still be a few years away, these results highlight that treatments targeting specific disabilities can actually repair the damage caused. Whilst holding strong potential to help stop the progression of the disease, neuroprotection treatments using gene focussed targeting could – based on these research outcomes – help people actually regain some lost function of any disability like sight, walking or cognition.

We look forward to seeing more research on this intriguing outcome!

everyone.org will keep you informed of any latest developments regarding neuroprotection or any new medications that become available.

References:

K.K. Jain, The Handbook of Neuroprotection, © Springer Science+Business Media, LLC 2011

1. Neuroprotection in the treatment of multiple sclerosis,
   Nervenartz, August 2011
2. Neuroprotection,
   Multiple Sclerosis Trust, April 2015
3. Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes,
   PNAS, January 2018