Neurological conditions affect the brain, spinal column and nervous system.
Here we focus on three of the most prevalent disorders impacting on lives throughout the UK, while taking a look at the treatments and developments which may offer hope for the future.
Parkinson’s disease is a complex condition with many physical and mental symptoms, but not every patient will experience all of them, and progression of the disease varies. Physical symptoms include tremors, muscle cramps, slowness of movement, rigidity and restless legs.
Parkinson’s can also cause other distressing symptoms, including anxiety, depression, dementia, hallucinations, delusions and memory problems.
Parkinson’s disease has no cure, although treatments are available which can help to alleviate symptoms and maintain quality of life.
The main drug used to treat the symptoms of Parkinson’s disease is levodopa. When dopamine levels in the brain become too low, because the dopamine-producing cells are dying or dead, Parkinson’s symptoms develop. Levodopa is a chemical building block that the body converts into dopamine. It can be used at all stages, usually starting with a low dose that is increased gradually until symptoms are controlled.
Dopamine agonists act like dopamine to stimulate nerve cells and come in various forms, such as tablets, capsules, prolonged release tablets, modified release tablets, pre-filled syringes and a skin patch. These treatments include Pramipexole, Ropinirole, Rotigotine, Apomorphine, Bromocriptine, Cabergoline and Pergolide, and can be used alone or alongside Levodopa.
MAO-B inhibitors work by blocking the monoamine oxidase type B (MAO-B) enzyme, which breaks down dopamine in the brain, to help nerve cells make better use of the dopamine that they already have.
In October, it was reported that researchers at Dundee University had solved the 3D structure of PINK1, a protein that plays a protective role in brain cells. Inherited changes in the PINK1 gene – that stop the protein from working – are known to be one of the most common causes of early-onset Parkinson’s.
The team used x-ray crystallography to make crystals of the protein and then used an x-ray machine to determine the 3D structure of the crystal. The researchers also found that PINK1 has unique control elements that allow it to interact with two other proteins, ubiquitin and Parkin, potentially paving the way to develop drugs that target the protective properties of PINK1.
Multiple sclerosis (MS) is a complex neurological condition with a number of symptoms that vary between patients. Common physical symptoms include vision problems, balance problems, stiffness, spasms, fatigue and dizziness. MS can also affect thinking, memory, emotions and mental health.
As well as recommendations on using diet, exercise, physiotherapy and complementary therapies to manage the symptoms of MS, disease modifying therapies (DMTs) are recommended for patients. DMTs reduce the number and severity of relapses, as well as slowing down the damage over time caused by relapses. They can’t, however, treat people who have MS without relapses. DMTs, which are taken in tablet or injection form depending on the drug, include: Lemtrada, Tysabri, Zinbryta, Tecfidera, Gilenya, Copaxone, Aubagio. There are five different beta interferons: Avonex, Betaferon, Extavia, Plegridy and Rebif.
Hope is on the horizon for those with progressive MS, as researchers at Roche and Genentech have developed a DMT for people with this form of MS, which it is hoped will be available by 2018. Ocrelizumab (Ocrevus) is the first treatment that can slow the advancement of primary progressive MS, according to the results of phase III trials. In March 2017 ocrelizumab was approved by the US Food and Drug Administration as a treatment for both relapsing and primary progressive MS, and in September Swiss regulatory authorities also approved it for the same indications. It is currently being reviewed by the European Medicines Agency, and a decision is expected in autumn 2017.
Cannabis and MS
The pain and muscle spasms associated with MS are exhausting and impact heavily on the sufferer’s quality of life, making daily tasks impossible. There are treatments available on the NHS, but they are ‘not appropriate, available or effective for all people with MS who experience these symptoms’, according to the MS Society. Evidence shows that cannabis for medicinal use can work for some people to relieve pain and muscle spasms in MS.
Bayer’s Sativex is a mouth spray which contains a medicine extracted from cannabis plants which offers relief from spasticity. It is not available on the NHS (apart from in Wales), and is expensive to buy privately. The MS Society is calling for the UK Government to make urgent changes to allow MS patients access to this medicine: ‘We are calling for the pharmaceutical company and the NHS to get back around the negotiating table to explore every possible avenue’, the Society stated in its ‘Cannabis and MS’ report from July 2017.
• 72% of people with MS feel that cannabis should be legalised for medicinal purposes
• 22% of people with MS have tried illegal forms of cannabis as they feel it is their only option.
Motor neurone disease
The Motor Neurone Disease Association explains MND and the treatments available.
MND is a fatal, rapidly progressing condition that involves the selective degeneration of motor neurones. It has a worldwide incidence of two per 100,000 and a prevalence of five to seven per 100,000. The only treatment currently licensed in the UK is riluzole, which is thought to work by suppressing glutamate activity. Riluzole is generally taken orally as a tablet (now off patent), however it has recently been formulated as a liquid (Teglutik). While the original trials showed that riluzole improved survival by two to three months, its true effects may be greater as its effects are masked by improvements in recent years by multidisciplinary team care and good symptom management (which also extends the lives of people with MND).
In May 2017 edaravone (trade name Radicava) was licensed for ALS (the most common form of MND) in the U.S. Clinical trials of edaravone have been limited to six months duration in a subgroup of patients, where the endpoints have been changes in a symptom management scale (the ‘ALSFRS’) rather than survival.
MND is a heterogeneous disease where the presentation and prognosis are difficult to predict for any one person with the condition. It is likely that a precision medicine approach may be successful in the future, identifying genetic subgroups of patients with specific, targeted treatments. A number of biological markers of progression are emerging which will be invaluable in such an approach.
Ian Hatton, 54, lives in Suffolk with his wife Karen and American Cocker Spaniel, Paxton.
In March 2016 I was sitting across the desk from my neurology consultant receiving the news that I had MND. I went through the process of asking standard questions about what I could expect and, more importantly, how long I had left.
I was told that most people with MND live two to five years. About 10% survive at least 10 years. A quick calculation told me that in the worst-case scenario it was possible that things could start going downhill very quickly.
It seems just ‘dumb luck’ with MND in terms of which functions and parts of the body are affected first and this obviously dictates how long people survive. I undergo all the standard tests on a regular basis to check physical symptoms and degradation, particularly with respect to breathing, but there is no test that can reliably forecast the rate at which the condition will progress and answer that key question of how much longer someone will be able to lead a relatively normal life. Psychologically I, and my family, find this is the most difficult challenge.
I actually feel very lucky and understand that there are many people much worse off than me. My wife Karen and family are very positive and we’re all determined to make the most of however much time we have together. Karen is a keen runner with several marathons under her belt, while she and friends have been involved with the MND Association to raise funds. The support I have received from this organisation, my consultant and all the specialist nurses and staff I see locally has been fantastic.
There are undoubtedly grim times ahead but to worry about something I cannot control would only have a detrimental effect on the time I have while relatively fit and healthy.
Go to mssociety.org.uk, mndassociation.org, parkinsons.org.uk