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Parkinson’s disease therapy pipeline offers promising new treatment hope

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It was in 1817 that Parkinson’s disease was first described as a neurological disorder.

In a detailed medical essay written by the London-based doctor who was to go on and give his name to the progressive disease, James Parkinson, he talked about the ‘shaking palsy’.

More than 200 years on, and whilst scientists have made huge leaps in understanding the neurodegenerative disorder, there is currently no cure. Treatments hinge on relieving symptoms with the limited drugs currently available, and maintaining quality of life.

Those drugs have largely remained unchanged for decades, however, and usually involve taking one called levodopa alongside other medications.

Game-changing therapies could soon be on the horizon, though, as scientists push the boundaries in the hunt for treatments that slow – or ideally reverse – the progress of Parkinson’s disease, which is caused by a loss of cells that produce the neurotransmitter dopamine.

This causes neurons to fire out of control, leading to Parkinson’s hallmark symptoms of tremors in the limbs and head, impaired balance, muscle stiffness, slowness of movement, and possible mental confusion and speech problems.

But according to business consultant and market research firm, DelveInsight, the Parkinson’s disease clinical trial pipeline space is brimming with novel emerging therapies with over 120 active players globally working to develop 140-plus treatments.

Key Parkinson’s disease companies currently working to improve the treatment landscape include Cerevel Therapeutics, Neuraly, Peptron, Biogen, Roche, Brain Neurotherapy Bio, United Neuroscience Ltd, Luye Pharma Group, Takeda, Xoc Pharmaceuticals, AstraZeneca, MedImmune, and Kissei Pharmaceutical.

In its Parkinson’s Disease Pipeline Insight – 2023 report,  DelveInsight says there are promising pipeline therapies in various stages of development.

These encompass Tavapadon, IkT-148009, NLY01, PT320, BIIB122, Prasinezumab, KDT-3594, AAV2-GDN, AKST4290, anle138b, ITI-214, NTCELL, Buntanetap, ANAVEX2-73, ATH-1017, NE3107, MEDI1341, AZD0328, Liraglutide, UB-312, LY03003, FB-101, AV-101, ABBV-951, NYX-458, DSP-9632P, Valiloxybate, SER-214, UCB7853, TAK-071, XC130-A10H, K0706, Talineuren, Pirepemat, Lu AF28996, WD-1603, CVN424, CST-103, NBTX-001, MSK-DA01, adipose-derived mesenchymal stem cells, ND0612, P2B001, 1ST-103, 1ST-105, and others.

In January this year, Neurocrine Biosciences and Voyager Therapeutics announced the formation of a new strategic collaboration to advance multiple gene therapies for the treatment of neurological diseases. 

The collaboration includes Voyager’s preclinical, intravenously administered GBA1 gene therapy programme for Parkinson’s.

In addition, Neurocrine Biosciences and Voyager have agreed to collaborate on three new gene therapy programmes directed to rare central nervous system (CNS) targets.

In October 2022, Biogen and Denali Therapeutics announced that dosing had commenced in the global Phase 3 Lighthouse study to evaluate the efficacy and safety profile of BIIB122 (DNL151), as compared to placebo in approximately 400 participants with Parkinson’s disease and a confirmed pathogenic mutation in the leucine-rich repeat kinase 2 (LRRK2) gene.

And, in September 2022, Neuron23, an early-stage biotechnology company focused on developing precision medicines for genetically defined neurological and immunological diseases, and QIAGEN, a provider of sample and assay technologies for molecular diagnostics, applied testing and academic and pharmaceutical research, announced a collaboration.

They are looking to develop a companion diagnostic for Neuron23’s LRRK2 inhibitor for Parkinson’s disease.

Other recent advancements cover Neuroderm’s liquid levodopa/carbidopa known as ND0612, which it was announced earlier this year had shown positive phase three trial results, and adipose-derived mesenchymal stem cells.

Stem cell therapy may benefit Parkinson’s disease by replacing and repairing damaged nerve cells within the brain.

Meanwhile Tavapadon, being developed by Cerevel Therapeutics, has shown improvements in movement symptoms.

The cause of Parkinson’s disease is still largely unknown. But it is a progressive disorder caused by nerve cell degeneration in the substantia nigra, a part of the brain that controls movement.

These nerve cells die or become impaired, losing the ability to produce dopamine, an important chemical.

Theories as to the potential causes of the disease involve oxidative damage, environmental toxins, genetic factors, and accelerated aging.

The majority of Parkinson’s patients are given medications to alleviate their symptoms. These work by either stimulating the remaining cells in the substantia nigra to produce more dopamine (levodopa medications) or inhibiting some of the acetylcholine produced (anticholinergic medications), restoring the balance of chemicals in the brain.

Many celebrities have been diagnosed with Parkinson’s and have been vocal about the condition, helping to raise its profile globally.

They include the Scottish comedian Billy Connolly, the actors Ian Holm, Bob Hoskins, Michael J Fox and Alan Alda, former US President George HW Bush, boxer Muhammad Ali, the singers Neil Diamond and Ozzy Osbourne, TV presenter Jeremy Paxman, and Pope John Paul II.

 

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Mole rat gene extends mouse lifespan

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A mole rat gene inserted into mice extended lifespan and improved health, findings that may point to new ways of supporting healthier ageing.

The gene increased production of a large form of hyaluronan, a naturally occurring gel-like substance between cells that helps tissue repair and cell-to-cell communication.

Mice carrying the naked mole rat version of the gene showed an approximately 4.4 per cent increase in median lifespan, alongside multiple markers of healthier ageing.

Naked mole rats have become a focus of ageing research because they combine an exceptional lifespan with unusual resistance to many age-linked diseases, including cancer.

Researchers at the University of Rochester traced part of that resilience to hyaluronan.

The molecule’s effects depend on its size: large forms are often linked to anti-inflammatory and tissue-protective behaviour, while smaller fragments can act as danger signals that increase inflammation.

Vera Gorbunova, professor of biology and medicine at the University of Rochester in the US, said: “Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals.”

The engineered mice were better protected against both spontaneous tumours and chemically induced skin cancer.

They also showed reduced inflammation across tissues, a notable finding because persistent low-grade inflammation, sometimes called inflammaging, is widely seen as one of the central drivers of age-related decline.

The research also linked the large form of hyaluronan to age-related gut health. As animals age, the gut barrier can become leakier, allowing inflammatory triggers to pass into the bloodstream.

The engineered mice showed protection against this deterioration.

Follow-up work found abundant high-molecular-mass hyaluronan across multiple species of subterranean mammals, often absent in closely related above-ground species, suggesting it may be part of a broader evolutionary toolkit for surviving long lives under harsh conditions.

The team said gene transfer is not the end goal. Gorbunova said: “It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice.”

“Our next goal is to transfer this benefit to humans.”

Two practical routes are being pursued: increasing production of the large form of hyaluronan, or slowing its breakdown.

Andrei Seluanov, who co-leads the research, said: “We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials.”

One candidate identified through screening is delphinidin, a plant pigment found in various fruits and vegetables.

In tests, it was found to increase levels of the large form of hyaluronan in cells and mouse tissues, reduce migration and invasion in multiple cancer cell lines, and suppress melanoma metastasis in mice.

However, the researchers acknowledged the approach has limits. A later study found that mice expressing the naked mole rat gene showed improvements in several late-life health measures but did not show protection from age-related hearing loss, suggesting some organs may be less reachable by this pathway than others.

The Rochester team said turning these findings into human therapies will likely depend on precision: maintaining the right molecular form of hyaluronan, targeting the right balance of production versus breakdown, and monitoring carefully for trade-offs as different tissues respond in different ways.

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AI can predict Alzheimer’s with almost 93% accuracy, researchers say

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Alzheimer’s AI can predict the disease with nearly 93 per cent accuracy using more than 800 brain scans, researchers say.

The system identified anatomical changes in the brain linked to the onset of the most common form of dementia, a condition that gradually damages memory and thinking.

The findings build on years of research suggesting AI could help spot early Alzheimer’s risk, predict disease and identify patients whose condition has not yet been diagnosed.

Benjamin Nephew, an assistant research professor at the Worcester Polytechnic Institute in Massachusetts, said: “Early diagnosis of Alzheimer’s disease can be difficult because symptoms can be mistaken for normal ageing.

“We found that machine-learning technologies, however, can analyse large amounts of data from scans to identify subtle changes and accurately predict Alzheimer’s disease and related cognitive states.”

The study used MRI scans, a type of detailed brain imaging, from 344 people aged 69 to 84.

The dataset included 281 scans showing normal mental function, 332 with mild cognitive impairment, an early stage of memory and thinking decline, and 202 with Alzheimer’s.

The scans covered 95 of the brain’s nearly 200 distinct regions and used an AI algorithm to predict patients’ health.

Being able to use AI to help diagnose Alzheimer’s earlier could give patients and doctors crucial time to prepare and potentially slow the progression of the disease.

The analysis showed that one of the top predictive factors was brain volume loss, or shrinkage, in the hippocampus, which helps form memories, the amygdala, which processes fear, and the entorhinal cortex, which helps provide a sense of time.

This pattern held across age and sex, with both men and women aged 69 to 76 showing volume loss in the right part of the hippocampus, suggesting it may be an important area for early diagnosis, the researchers noted.

However, the research also found that the way brain regions shrink differs by sex.

In females, volume loss occurred in the brain’s left middle temporal cortex, which is involved in language and visual perception. In males, it was mainly seen in the right entorhinal cortex

The researchers believe this could be linked to changes in sex hormones, including the loss of oestrogen in women and testosterone in men.

These conclusions could help improve methods of diagnosis and treatment going forward, Nephew said.

More than 7.2m Americans are living with Alzheimer’s, according to the Alzheimer’s Association.

More research is being done to reveal other impacting factors.

Nephew said: “The critical challenge in this research is to build a generalisable machine-learning model that captures the difference between healthy brains and brains from people with mild cognitive impairment or Alzheimer’s disease.”

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Vision implant firm raises US$230m

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A vision implant firm has raised US$230m as it seeks approval in Europe and the US for a device that restored sight in a small clinical trial.

The Alameda, California-based startup said the funding would support commercialisation of its Prima device.

It said an upcoming launch is planned in Europe and that it would become the first brain computer interface company to have a vision restoration device on the market.

A clinical trial in Europe found the small implant could work as artificial photoreceptors in the retina to restore functional central vision.

The implant is placed under the retina to replace the function of light-sensitive cells lost to disease. A special pair of glasses with an embedded camera and infrared projector sends light signals to the implant.

The study assessed the system in people with advanced dry age-related macular degeneration.

Of the 38 patients who received an implant, 32 were assessed at 12 months. Results showed the device led to a clinically meaningful improvement in visual acuity in 26 people.

The patients were able to read letters, numbers and words, according to the company.

Science Corporation said it has submitted a CE mark application to the European Union and applied to the US Food and Drug Administration for regulatory approval.

Darius Shahida, chief strategy officer, said: “Our imperative is to become the first BCI company to scale and achieve profitability.”

Founded in 2021, the company has now raised about US$490m in total. It said it is expanding its clinical trial programme to include other retinal diseases, such as Stargardt disease and retinitis pigmentosa.

The Series C round included existing investors Khosla Ventures, Lightspeed Venture Partners, Y Combinator, IQT and Quiet Capital.

Science Corporation said demand for the round exceeded its capital needs, with funds also earmarked for expanding research, manufacturing infrastructure and operations.

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