SCOTTISH HOSPITAL NEWS
PREDICTING COGNITIVE DEFICITS IN PEOPLE WITH PARKINSON’S DISEASE
Parkinson’s disease is commonly thought of as a movement disorder, but, after years of living with the disease, approximately 25 per cent of patients also experience deficits in cognition that impair function. Now, a newly-developed research tool may help predict a patient’s risk for developing dementia and could enable clinical trials aimed at finding treatments to prevent the cognitive effects of the disease. The research was published in Lancet Neurology and was partially funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
‘This study includes both genetic and clinical assessments from multiple groups of patients, and it represents a significant step forward in our ability to effectively model one of the most troublesome non-motor aspects of Parkinson’s disease,’ said Margaret Sutherland, PhD, programme director at the NINDS.
For the study, a team of researchers led by Clemens Scherzer, MD, combined data from 3,200 people with Parkinson’s disease, representing more than 25,000
individual clinical assessments and evaluated seven known clinical and genetic risk factors associated with developing dementia. From this information, they built a computer- based risk calculator that may predict the chance that an individual with Parkinson’s will develop cognitive deficits.
‘By allowing clinical researchers to identify and select only patients at high-risk for developing dementia, this tool could help in the design of ‘smarter’ trials that require a manageable number of participating patients,’ said Dr Scherzer.
Moving forward, Dr Scherzer and his colleagues from the International Genetics of Parkinson’s Disease Progression (IGPP) Consortium plan to further improve the cognitive risk score calculator. The team is scanning the genome of patients to hunt for new progression genes. Ultimately, it is their hope that the tool can be used in the clinic in addition to helping with clinical trial design. However, considerable research remains to be done before that will be possible.
COMBINATION THERAPY
SHOWN TO SHRINK TUMOURS Bristol-Myers Squibb has announced efficacy and safety data from CheckMate 204, the first Phase II study evaluating the cancer immunotherapy combination of nivolumab plus ipilimumab in adult patients with advanced melanoma that has spread to the brain (metastasised).
In the study (n=75), 60 per cent of patients treated with combination therapy achieved intracranial (IC) clinical benefit (defined as complete response plus partial response plus stable disease ≥ 6 months) 95% CI: 48 - 71).
The combination therapy also demonstrated that over one fifth (21 per cent) (n=16) of patients achieved
a complete IC response – meaning there was no detectable sign of the cancer in their brain remaining.
Additionally, the data showed that 33 per cent of patients (n=25) achieved partial responses (significant tumour reduction) and five per cent (n=4) experienced stable disease (no progression in tumour growth).
More than 60 per cent of advanced melanoma patients will develop brain metastases, and in these cases prognosis is poor. These nivolumab plus ipilimumab data were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017.
NEW CLINICAL STUDY ON NEW TREATMENT FOR PARACETAMOL POISONING
A clinical trial for Aladote®, a new treatment for reducing liver damage from paracetamol (acetaminophen) poisoning, has begun at Edinburgh Royal Infirmary. The trial of 24 patients is evaluating the safety and tolerability of Aladote® in combination with the current standard treatment (N-acetylcysteine) for the prevention of acute liver failure due to paracetamol poisoning. Paracetamol poisoning affects approximately 50,000 people in the UK every year.
The clinical study is being run by PledPharma in collaboration with the University of Edinburgh, under the direction of Dr James Dear, Reader in Pharmacology at the University of Edinburgh, and specialist in paracetamol poisoning.
Preclinical animal studies have suggested that the new drug (active ingredient calmangafodipir) may be effective at reducing liver damage in the period more than eight hours after a paracetamol overdose, where N-acetylcysteine is minimally effective.
’During the first 24 hours after paracetamol poisoning people
usually experience few or no symptoms,’ said Dr Dear, principal investigator and Reader in Pharmacology at the University of Edinburgh. ’Therefore, many patients come to hospital at such a late stage that the current standard treatment is not sufficient to prevent acute liver failure. Calmangafodipir has in preclinical studies demonstrated impressive results even in the late stages of the poisoning process, and I look forward to the results of this important proof-of-principle study.’
Paracetamol poisoning is the most common cause of acute liver failure in the US and Europe. It is the drug most commonly taken in overdose in the UK, and there are an estimated 50,000 emergency hospital admissions and approximately 200 deaths due to paracetamol poisoning in the UK every year.
The new treatment would be a great step forward in both saving lives and cutting NHS costs, as many paracetamol poisoning patients do not present at hospital until more than eight hours after their overdose, leaving them at considerable risk of severe liver damage.
‘The combination of nivolumab plus ipilimumab has completely transformed how we treat and manage advanced melanoma over recent years and has fundamentally changed survival expectations for these patients,’ commented Professor John Wagstaff, Professor of Medical Oncology, College of Medicine, Swansea University.
‘One of the most difficult circumstances in these patients is when the disease progresses to the brain. In these cases, the outlook is generally very poor and treatment limited. These data are therefore really promising and show the potential using immunotherapy can have in wiping out tumours even in some of the most difficult-to-treat patients.’
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