British gene jab offers new hope for Parkinson’s patients | UK | News

British-led gene therapy that rewires the brain’s circuits has been hailed as a “game changer” for millions of people suffering from Parkinson’s disease.

A small one-time injection deep into the brain could usher in a “new era” in the treatment of the disease, which affects more than 160,000 patients in the UK, scientists say.

Trials have shown the new treatment “resets” faulty wiring, helping patients move properly again – and early evidence suggests it may also slow the disease itself.

“This is one of the most exciting things we’ve done,” said Dr Alexandria “Zandy” Forbes, boss of London biotech firm MeiraGTx. “Using artificial intelligence, we found that our therapy changes the brain in a way that allows people to move, but can also slow degeneration. This is truly a breakthrough.”

The therapy, known as AAV-GAD, has been tested in three groundbreaking early-stage studies in Parkinson’s patients. 14 patients were involved in the latest operation, which delivers a missing gene directly to the brain to reprogram nerve cells and calm the tremors and stiffness that make daily life so difficult.

The patients were divided into three groups; five received a high dose, five a low dose, and four a sham (sham) procedure.

After six months, those treated with the high dose improved by an average of 18 points on the gold standard Parkinson’s movement scale. Only a five to ten point change is considered medically significant.

In contrast, no significant improvement was seen in the low-dose and placebo groups.

Principal investigator, neuroscientist and Director of the US Rockefeller Institute for Neuroscience in West Virginia, Dr. Ali Rezai said:

“These safety and outcome results are excellent. The extent of improvements in motor scores in patients receiving high-dose therapy is highly encouraging for both patients and physicians, with significant quality-of-life improvement measures.”

He said this was the first clear sign that a single gene therapy could make a measurable difference in real-world function.

After the initial mobility gains were recorded, the scientists sent brain scans to artificial intelligence experts at University College London for independent analysis.

This confirmed that the circuits in the brain were physically changing; This suggests that the therapy rebalances brain networks that become out of control in Parkinson’s disease.

“We provided data from patients’ brain scans before, during and after treatment,” Dr Forbes said.

“The group from UCL and (AI company) Hologen were able to use their AI to look at the brain and show that we physically altered the circuits of the Parkinson’s patients we treated.”

AI analysis showed calming signals spreading to other brain regions, including the substantia nigra, the area where Parkinson’s disease begins and dopamine-producing cells die.

Parkinson’s prevents people from moving by killing dopamine-producing cells that control the body’s coordination. Without dopamine, the brain’s subthalamic nucleus, a region that regulates movement, goes into overdrive, sending out bursts of the chemical glutamate that causes tremors and stiffness.

Instead of supplementing dopamine, MeiraGTx’s therapy reverses the chemistry by delivering a gene called GAD (glutamic acid decarboxylase) to an overactive brain area.

The gene produces an enzyme that converts glutamate into GABA, the brain’s natural calming signal. This restores balance in the motor circuits and smoothes the movement.

“By silencing the circuits, we changed the physiology of the brain and saw improvements in movement,” Dr Forbes said.

The AI ​​data also suggested that the therapy did more than just aid movement; It appears to positively influence connections in areas linked to mood and memory, raising hopes that it could help with the depression and cognitive problems that often accompany Parkinson’s disease.

This is not MeiraGTx’s first success. The company has previously worked with Moorfields Eye Hospital in London to restore sight to blind children using a similar gene therapy approach.

“We treated children who were all born blind due to the lack of a single functional gene. When we transferred an accurate copy of the gene into the retina of these young children with a one-time injection, each treated child gained sight and their lives were transformed,” Dr Forbes said.

Now the MeiraGTx team, based in Shoreditch, east London, is preparing for a large-scale global trial to confirm the Parkinson’s results.

People who no longer respond to medication and cannot receive effective long-term medical treatment will participate in the study.

If successful, this gene therapy treatment could be the first to both restore movement and slow the progression of the world’s fastest-growing neurological disease.

“These are really important stories,” Dr Forbes said. “This is science that has the potential to literally transform the lives of these patients and provide hope for millions of patients for whom no other effective treatments are available.”

Parkinson’s affects around 168,000 people in the UK and numbers are rising.

The results mean MeiraGTx’s treatment has now been granted accelerated status by the US regulator FDA, paving the way for a late-stage trial that could potentially support approval.

“This could be the beginning of a new era,” Dr Forbes said. “For the first time, we are seeing a significant improvement for this condition as well as a physiological change in the brain after a one-time gene therapy treatment.”