Huntington’s result 'could boost' ALS/frontotemporal dementia therapy

Neil Ward, the company’s VP/general manager EMEA, said that until now many individuals at risk from Huntington's had not been offered testing or chose not to pursue it, owing to the lack of viable treatment .

However, the recent breakthrough could change this, he suggested, giving people a reason to seek testing and could inform family planning decisions.

Equally important, Ward said, it demonstrated what advances could be possible in fighting other devastating genetic disorders.

“Huntington’s is just one of a wider group of ‘repeat expansion disorders’, caused by stretches of repeated DNA that can disrupt how genes work. While Huntington’s is relatively straightforward to study, many other conditions have been out of reach for research and testing,” he remarked.

Ward said this was because repeats are too long or numerous for older genomic technologies and required multiple tests that were not practical for “resource-pressured” national health systems.

“Advances in sequencing technology now make it possible to study and diagnose these conditions in a single test, opening the door to more timely diagnoses and, ultimately, new therapies that could change lives across many families,” he commented.

He specifically cited current UK clinical trials being conducted by Wave Life Sciences. Ward said these are looking at expansions in the C9orf72 gene associated with conditions such as ALS and frontotemporal dementia.

Advances in sequencing technology now make it possible to study and diagnose these conditions in a single test, opening the door to more timely diagnoses and, ultimately, new therapies that could change lives across many families

Neil Ward, VP/general manager EMEA, PacBio

Results from the recently published global Huntington’s drug trial, involving 29 patients, demonstrated on average a slowdown in disease progression three years. The surgery used the AMT-130 gene therapy developed by sponsor, the Netherlands and US based company uniQure.

Mutations of the Huntingtin (HTT) gene creates misfolds in huntingtin protein which disrupt neurons to enable symptoms of Huntington’s disease. Children of sufferers have a 50% chance of inheriting the condition.

Lead scientific adviser professor Sarah Tabrizi, director of the University College London Huntington's Disease Centre and her colleagues employed a safe virus to deliver a DNA sequence to the brains of participants.

The process is designed to prompt microRNA production to prevent messenger RNA being sent from cells' DNA to stimulate the creation of mutant huntingtin.

The treatment is intended to permanently lower levels of mutant huntingtin with one dose. Those clinical trial patients who received a high dose of AMT-130 experienced 75% less disease progression.

Researchers also measured levels of neurofilament light protein (NfL) released into spinal fluid to counter neuron injury.

People with Huntington’s disease normally have raised levels of NfL and this would be expected to have risen 20-30% over the three year period reviewed.

Instead, the scientists discovered that NfL levels in the spinal fluid of the therapy patients were lower than at the start of the trial, proving they say that the progress of Huntington’s was modified and neuronal damage slowed.

For further information on the Huntington's clinical trial, click here.

Pic: Anna Shvets