Neuralgene, a startup biotech company, will begin animal studies in May to evaluate the efficacy of PRCN-829, its new gene therapy agent for the treatment of amyotrophic lateral sclerosis (ALS). PRCN-829 is the first gene therapy for sporadic ALS.

Neuralgene’s neurotropic AAV-based gene therapy platform for the treatment of neurodegenerative diseases is based on the stem cell work performed by Jason Williams, MD, founder and CEO of Neuralgene.

Leonardo Gonzalez, MD, clinical researcher for Neuralgene said, “This technology addresses several key aspects of the underlying pathology of ALS.” Gonzalez further added, “In his stem cell work, Dr Williams had identified that production of Factor H by fat-derived mesenchymal stem cells may be a key mode of action.”

The gene therapy is based on Dr Williams’ discovery that certain proteins produced by stem cells inhibit the attack of ALS. During the development of the gene therapy, he added new targets: neural growth factors and a protein implicated in ALS named TDP-43. Dr Gonzalez stressed, “When Dr Williams demonstrated the concept behind stem cells and how to address the treatment of ALS using gene therapy, we immediately knew that this was a revolutionary new concept.”

The PRCN-829 gene therapy is designed to not only target gene delivery to the brain and spinal cord, but also to genetically engineer stem cells. The AAV9 viral vector delivers multiple genes, which include Factor H (a regulator of complement activity), neural growth factors and regulators of TDP-43, to the neural cells. Initial animal studies have demonstrated the safety of the gene therapy platform.

The AAV9 viral vector delivers to the neural cells multiple genes which include Factor H (a regulator of Complement), neural growth factors and regulators of TDP-43.

“The problem with stem cell therapy for ALS is that the results are generally partial and temporary,” stated Dr Williams. “This is because the stem cells produce the growth factors and other proteins for a short period, but then cease. Several stem cell studies have confirmed this. Now with gene therapy, we can increase those factors by a millionfold or greater so that recuperation lasts for many years, maybe even lifelong.”

PRCN-829 can also be used to genetically engineer stem cells. The stem cells then produce the beneficial proteins and neural growth factors.

“ALS is a complex disease with many different underlying causes,” continued Dr Williams. “Our gene therapy will target several of the main underlying mechanisms related to ALS with the hopes of getting a good response in a larger group of patients. However, our platform is versatile, allowing us to change and add different target genes. We expect that soon we will be able to perform a detailed genetic analysis of the patient, identifying their exact underlying cause of ALS. Then we will be able to tailor the therapy to each individual patient.”

The company has partnered with several labs for the development of its patent-pending neurotropic AAV-based gene therapy for the treatment of neurodegenerative diseases such as ALS. In fact, Neuralgene partnered with Dr Williams’ imaging and image guided treatment facility, Precision StemCell in Bogota, to begin studies using image-guided administration of gene therapy to the spinal cord.

“This is a completely new therapy for ALS, and the groundwork for this technology will lead to the treatment of many other diseases,” said Dr Williams. Neuralgene has several other AAV gene therapies in its research and development pipeline for the treatment of neurodegenerative diseases such as Parkinson’s and Multiple Sclerosis (MS). After initial testing of PRCN-829 in Colombia, Neuralgene plans to seek approval from the FDA for trials in the United States.

Neuralgene is focused on AAV gene therapy, which produces multiple proteins for the treatment of neurodegenerative disorders such as ALS and Parkinson’s.