Sniffing out Parkinson’s Disease
April 3, 2019 | Disease
The number of people suffering from Parkinson’s disease, already over 10 million worldwide, is set to double within 50 years as populations age. This chronic, progressive condition is caused by the degeneration of dopamine-producing cells in the brain, leading to both physical and cognitive symptoms. Parkinson’s patients may experience tremors, difficulties walking and moving normally, mood-changes and sleep disturbances, making their lives miserable. The disease is not in itself fatal. But its consequences can be.
The most effective treatment today is levodopa, a chemical developed 60 years ago. It converts in the body into dopamine, the neurotransmitter that Parkinson’s patients lack. Several brands are available including Sinemet, Duopa and Parcopa.
But Levadopa has side-effects, and does not address the root causes of Parkinson’s. And it is often administered too late to meaningfully reduce symptoms. Parkinson’s can be tricky to diagnose early, before significant neural damage occurs.
A handful of new approaches, from antibodies to cell- and gene-replacement, may help to stop – and even reverse – the brain damage characteristic of Parkinson’s. Some target alpha-synuclein, a protein that mis-folds to form clumps called “Lewy bodies” in parts of the brain. These clumps are thought to contaminate normal, healthy neurons, causing wider damage.
Biogen’s antibody, BIIB054, is designed to target the mutated forms of alpha-synuclein, thereby reducing the spread of Lewy bodies. A Phase II trial is recruiting. Meanwhile, scientists continue to work on ways to transplant dopamine-producing cells, grown from stem cells ex-vivo, into the brain. Various clinical trials are underway. Researchers at Edinburgh University are using gene-editing tools like CRISPR to strip out the DNA thought to be responsible for abnormal alpha-synuclein and Lewy body formation. Such ‘Lewy-resistant’ cells may help limit the spread of neuronal damage, making cell-therapy approaches more effective and long-lasting.
The gene-therapy revival has also reached Parkinson’s. Voyager Therapeutics’ VY AADC, which carries the gene for an enzyme involved in dopamine production, is beginning Phase II/III testing. The therapy is injected directly into the region of the brain where the neurotransmitter is normally active. A Phase Ib trial of 15 patients showed a reduced need for levodopa treatment and improved motor function and quality-of-life scores in some patients. Axovant Sciences’ AXO-Lenti PD, licensed from Oxford BioMedica, recently began a Phase II clinical trial in the UK. This product delivers genes for three enzymes required for dopamine production. The hope is that a single administration of such gene therapies may provide multi-year benefits to patients – though longer-term safety and efficacy data is required to prove that.
Meanwhile, Parkinson’s may soon be much easier to catch early – using our noses. In a widely-reported story, former nurse Joy Milne was able to smell a musty scent on her husband over a decade before he was diagnosed. She noticed in support group meetings that everyone smelt the same. Scientists are now looking to isolate substances in sebum – oily secretions from our skin – that may provide an early-warning of the condition, allowing early intervention to protect dopamine-producing cells before they die. One candidate substance that may be causing the aberrant smell: alpha-synuclein.
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