Staff Services Student Enterprise

Neurogene announces Rett syndrome candidate treatment

19 May 2022

US biotech company Neurogene has announced that a new 'product candidate' for the treatment of Rett syndrome has been added to its development pipeline.

The potential gene therapy, NGN-401, is based on research by Dr Stuart Cobb, Reader in Neuroscience at the University of Edinburgh's Centre for Discovery Brain Sciences, and is the company's first potential treatment produced by the Expression Attenuation via Construct Tuning (EXACT) gene regulation platform.

Dr Cobb, who is also Neurogene's Chief Scientific Officer, established a multi-year collaboration agreement between the University and Neurogene in 2021, with Edinburgh Innovations' support, and has been working with the company since 2018.

Progressive disorder

Rett Syndrome is a progressive neurodevelopmental disorder estimated to affect 1 in 10,000 girls, making it one of the most common genetic causes of developmental and intellectual impairment in females. The incidence in males is currently unknown.

Currently, there are no approved disease-modifying therapies, and treatment for Rett syndrome includes symptom management and supportive care.

Rett syndrome is caused by mutations in the MECP2 gene that leads to deficiency of the methyl cytosine binding protein 2 (MeCP2), an important protein responsible for normal neural development and signalling in the brain and other parts of the nervous system.

NGN-401 has been shown in preclinical models to deliver efficacious levels of MeCP2, while avoiding toxicity observed with conventional MECP2 gene therapy. EXACT is a self-regulating gene therapy platform that can be tuned to deliver the desired level of transgene expression within a narrow range and is compatible with viral and non-viral delivery platforms.

Dr Stuart Cobb said:

Rett syndrome is a complex disorder not readily addressable by conventional gene therapy because the MECP2 gene is toxic if expressed at high levels.

As someone who has been working in Rett syndrome research for more than 15 years, I am pleased that NGN-401, our lead program utilizing EXACT technology, has demonstrated a significant survival benefit and reduced disease burden in a robust preclinical Rett model.

Research Trust

Dr Cobb’s laboratory has been collaborating with the Rett Syndrome Research Trust (RSRT) and numerous researchers in the field to develop a gene therapy with a strong profile to advance to the clinic.

Monica Coenraads, CEO of RSRT, said:
We are thrilled that NGN-401 has demonstrated promising preclinical results. RSRT’s long-term support of Dr Cobb’s laboratory at the University of Edinburgh demonstrates our commitment to drive innovation in research for Rett Syndrome.

We hope this novel approach will continue to advance in its development and ultimately provide a much-needed treatment option for families impacted by Rett syndrome.

Photograph shows Dr Stuart Cobb, back row farthest left, with his research team at the Centre for Discovery Brain Sciences.

Related links


The Centre for Discovery Brain Sciences

Rett Syndrome Research Trust