De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms.

The CDKL (cyclin-dependent kinase-like) family consists of five members in humans, CDKL1-5, that encode serine-threonine kinases. The only member that has been associated with a Mendelian disorder is CDKL5, and variants in CDKL5 cause developmental and epileptic encephalopathy type 2 (DEE2). Here, we study four de novo variants in CDKL2 identified in five individuals, including three unrelated probands and monozygotic twins.

Standards and infrastructure for multisite deployment of the research participant perception survey.

Objectives: To develop and disseminate a technical framework for administering the Research Participant Perception Survey (RPPS) and aggregating data across institutions using REDCap.

Materials And Methods: Six RPPS Steering Committee (RSC) member institutions met bi-weekly to achieve consensus on survey sampling techniques, data standards, participant and study descriptor variables, and dashboard design.

Results: RSC members implemented the infrastructure to send the RPPS to participants and shared data to the Empowering the Participant Voice Consortium Database.

CNM-Au8 in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial.

Importance: Bioenergetic failure has been proposed as a driver of amyotrophic lateral sclerosis (ALS). CNM-Au8 is a suspension of gold nanocrystals that catalyzes the conversion of nicotinamide adenine dinucleotide hydride into NAD+, resulting in an increase of cellular adenosine triphosphate production.

Objective: To determine the effects of CNM-Au8 on ALS disease progression.

Pridopidine in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial.

Importance: Amyotrophic lateral sclerosis (ALS) is a fatal disease. The sigma-1 (σ1) receptor emerged as a target for intervention.

Objective: To determine the effects of pridopidine, a σ1-receptor agonist, in ALS.

Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial.

Importance: Myeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.

Objective: To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.