Familial dysautonomia (FD) is an autosomal recessive neurodevelopmental disorder.

A recent study published in PLOS Genetics has identified several novel genetic variants associated with the risk of orofacial clefts, a common and complex congenital disability. Orofacial clefts are caused by a combination of genetic and environmental factors and can occur in isolation or simultaneously with other birth defects.

Some 1 million people around the world suffer severe neurological problems, such as epilepsy, motor impairment and cognitive dysfunction, because they express insufficient SynGAP1, a GTPase-activating protein that operates postsynaptically. Current therapies can mitigate symptoms but not cure the underlying disease. Researchers at the Allen Institute and collaborators have demonstrated a potential genetic cure for SynGAP1 deficiency.

A preclinical study presented at the 32nd Annual Congress of the European Society of Gene and Cell Therapy (ESGCT), held in Seville Oct. 7-10, showed a new epigenetic editing technology that enables durable gene silencing using ELXRs, short for Epigenetic Long-Term X-Repressors. With this approach, scientists at Scribe Therapeutics Inc. successfully inhibited the expression of the PCSK9 gene, a key regulator of cholesterol metabolism, in human cells, mice and nonhuman primates.

Angelman syndrome is a rare genetic, nondegenerative and neurodevelopmental disorder caused by mutations affecting the expression of maternal UBE3A, which is expressed in neurons and is a key protein for neuronal morphology and correct synaptic functioning. The disease is characterized by intellectual disability, defects in movement and sleep disruption, among others.

While recent advances in gene therapy have offered unprecedented options for patients with hemophilia, new data presented at the 32nd Annual Congress of the European Society of Gene and Cell Therapy (ESGCT), held in Seville Oct. 7-10, revealed persistent concerns regarding the durability of these treatments and their potential liver toxicity.

The transition from complex and costly ex vivo strategies to platforms that enable direct cellular intervention within the body, known as in vivo therapies, is marking a paradigm change in the field of gene and cell therapies by simplifying manufacturing, improving tissue targeting and expanding clinical access to treatments.

As the many challenges facing cell therapies are being addressed, the CAR T field continues to evolve beyond its original design of T cells engineered to target hematological malignancies. During the 32nd Annual Congress of the European Society of Gene and Cell Therapy (ESGCT), held in Seville Oct. 7-10, several studies showed how this technology is being redefined as programmable and adaptable immune cells with expanded functional versatility.

Genetic mutations are the primary cause of most rare diseases. Although each condition affects a small fraction of the population, the global impact is significant, with an estimated 300 million individuals affected worldwide. A large proportion of pathogenic missense variants – estimated at 40%-60% – cause rare diseases by impairing protein stability. This underscores protein restoration as a promising therapeutic strategy.