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HomeBlogFinding new ways to connect Parkinson’s neurological dots

Finding new ways to connect Parkinson’s neurological dots

By: Medix Team
Finding new ways to connect Parkinson’s neurological dots

Can scientists slow down or stop the world’s fasting growing neurodegenerative disease in its tracks?

Deng Xiaoping and George H.W. Bush have a lot more in common than being the respective former leaders of China and the US. They were also both sufferers of different forms of Parkinson’s disease.

 

It’s a difficult disease to diagnose, especially the form that Deng had, as it usually develops gradually over time. Non-motor symptoms such as mood swings and memory lapses apply to lots of different conditions and often predate a formal diagnosis by up to two decades.

 

It’s only when motor problems such as involuntary movement (dyskinesia), tremors, muscle rigidity and slow movement (bradykinesia) become more evident that physicians are likely to pinpoint the cause. By this point, sufferers may have lost up to 80% of their dopamine-producing neurons, which the nervous system uses to send messages between nerve cells.

 

The degenerative disease has officially had a name since 1817 when British doctor James Parkinson wrote a paper about shaking palsy. But its symptoms have been evident since the dawn of medicine.

 

The ancient Greek physician Galen wrote about it. So did ancient practitioners of Traditional Chinese Medicine (TCM) and Ayurveda who respectively referred to wind shaking syndrome and kampavata. 

 

There are currently about 10 million Parkinson’s patients worldwide and their number doubled between 1990 and 2016. Another doubling is forecast between 2016 and 2030. By then, China is expected to account for more than half of all global cases.

 

Elevated risk with Type-2 diabetes

 

Scientists are still not sure what causes Parkinson’s, although they have identified many risk factors. They have, for example, studied 400 genes, which may predispose individuals to both Parkinson’s and Type-2 diabetes.

 

They also believe there are environmental factors at play, since ethnicity seems to count for less than where someone lives. Traditionally, that’s meant more cases in Western countries. However, the rise of lifestyle diseases such as Type 2 diabetes in Asia suggests the region may well catch up, or even overtake the West.

 

A landmark 2018 Study by the University of London (UCL) revealed that people with Type 2 diabetes are one third more likely to get Parkinson’s. The risk factor increases fourfold for those aged 25 to 44.

 

Scientists believe this relates to diabetics’ resistance to insulin, the hormone that converts glucose into the energy, which our brain cells rely on. But this link also opens up new treatment avenues, as there’s growing evidence that certain diabetic drugs help Parkinson’s sufferers too.

 

For instance, the same UCL researchers are running phase III clinical trials on the efficacy of the diabetes drug Exenatide, which stimulates insulin release. Phase II results revealed that Type-2 diabetics were 60% less likely to develop Parkinson’s after taking it.

 

Stopping the shaking

 

April is World Parkinson’s Month in honour of James Parkinson’s birthday on the 11th. It also has an official symbol to raise awareness – a red tulip with a white fringe in honour of the Dutch horticulturist and Parkinson’s sufferer who developed it. 

 

Over the past year, potential breakthroughs have come thick and fast. They’ve been a long time coming.

 

Right now, the main treatment is a drug called Levodopa, which was developed in the 1960’s, although ayurvedic doctors have been prescribing mucuna pruriens for centuries. The bean, which grows widely across the tropics, is rich in natural Levodopa.

 

But there are side effects to taking Levodopa, which is converted into dopamine in the brain. Oral administration means it’s absorbed into the bloodstream, causing peaks and troughs in absorption rates.

 

More importantly, it also causes shaking after long-term treatment. This affects about half of patients within five years and 80% within 10. Many sufferers say they find the shaking even worse than the disease itself.

 

So the announcement of a potential breakthrough last year caused plenty of news headlines. A US biotech launched the first human trials of a drug called NLX-112.

 

This targets the nerve cell chemical serotonin, which may trigger dyskinesia by causing erratic dopamine release. In 2019, scientists also flagged decreasing serotonin levels as an early indication of Parkinson’s.

 

NLX-112 stopped the shaking in monkeys and could become available within a year. However, there’s one caveat: there’ve been plenty of successful trials on monkeys for neurological drugs before that subsequently didn’t work well on humans.

 

Clinical trials are also ongoing for the use of focused ultrasound (FUS) to treat dyskinesia (it’s been approved for tremors since 2018). Doctors shoot highly targeted beams deep into the brain to destroy brain cells that cause movement problems.

 

FUS is cheaper and less invasive than deep brain stimulation (DBS), which has been used since 1997. DBS sees electrodes inserted into the brain, which are then connected to an IPG (implantable pulse generator) placed under the collarbone, or abdomen. The latter acts like an on/off switch, controlling motor function.

 

Parkinson’s and TCM

 

Many patients find non-medical treatments, such as ballet and tai chi, help to improve balance and co-ordination. Studies also show that about three-quarters of East Asian patients turn to TCM, including acupuncture (seven acupoints on the cranial base can alleviate rigidity) and acumassage.

 

Studies suggested potential efficacy of two TCM drugs. Yanggan Xifeng has synergistic effects alongside Levodopa, while Zishenpingchan granules, which nourish the kidney and liver, alleviate Levodopa’s side effects.

 

Doctors are also getting better at diagnosing the disease. The Michael J Fox Foundation and Parkinson’s UK funded a clinical trial that could lead to a simple skin test.

 

About 60% of people with Parkinson’s get oily skin (seborrhoeic dermatitis). The new test analyses compounds in sebum, the oily substance that protects and coats it.

 

Precision medicine

 

Earlier diagnosis should not only help patients to get treatment sooner, but also lead to a better understanding of the disease and the potential for precision medicine to control or cure it. 

 

One promising line of treatment is immunotherapy. Parkinson’s causes inflammation in the brain, but a link’s been established with raised inflammation markers in the blood too. Cambridge University is trialling Azathioprine, an anti-inflammatory drug used to treat rheumatoid arthritis and Crohn’s disease.

 

Gene therapy offers the potential to insert genes that promote dopamine synthesis.  US and UK biotech Sio Gene Therapies and Oxford Biomedica are trialling a gene therapy, AXO-Lenti-PD, that involves transferring three enzymes critical to the process (hyperlink 15).

 

One feature that Parkinson’s shares with another neurological disease, Alzheimers, is the way that proteins ended up clumping on the brain: alpha-synuclein for Parkinson’s and beta-amyloid for Alzheimers.

 

Multiple drug companies are conducting trials on drugs to break these clumps up. Switzerland’s Hoffman-La Roche has completed a Phase I trial for a drug that led to a 97% reduction.

 

Overall $1 billion of Parkinson’s funding has, so far, come from the Michael J. Fox Foundation. The former US actor is arguably the world’s most famous sufferer and driving efforts to find a cure. “To me hope is informed optimism,” he once concluded.



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