FDA Grants BREN-02 Orphan Drug Designation, Memory Preservation in Primary Progressive Aphasia, Phenotypes of MS

This week Neurology News Network covered the orphan drug designation of BREN-02 in amyotrophic lateral sclerosis (ALS), memory preservation as a core feature of primary progressive aphasia, and a deeper look at phenotypes of patients with multiple sclerosis (MS).

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the NeurologyLive team, moves to working remote as we come together to help reduce the spread of the novel coronavirus.

Recently, BrainEver announced that the FDA granted orphan drug designation to its investigational product, BREN-02, the recombinant human homeoprotein Engrailed 1 (rhEN1), for the treatment of amyotrophic lateral sclerosis. The product is expected to be initiated into clinical trials with patients with ALS in the second half of 2021, subject to preclinical toxicity results and regulatory review. Preclinical studies have demonstrated that the homeoprotein EN1 plays a role in the survival and maintenance of motor neuron-alpha spinal cells that innervate skeletal muscles.During development, homeoprotein intercellular transfer influences cell migration and axon guidance whereas, at post-natal and adult periods, it controls cerebral cortex neuronal network plasticity. The company noted that these homeoproteins can also boost mitochondrial metabolism, participate in the maintenance of physiological epigenic marks, and limit the formulation of DNA breaks—a hallmark of aging.

Longitudinal analysis from a group of researchers at Northwestern University Feinberg School of Medicine demonstrated that memory preservation in patients with primary progressive aphasia (PPA) is not just an incidental finding at onset, but a core long-term feature despite hippocampo-entohinal Alzheimer disease (AD) neuropathology that is as severe as that of amnestic dementia with AD. Among a cohort of 17 PPA patients with autopsy or biomarker evidence of AD (PPA-AD), episodic memory, tested with nonverbal items, was preserved at initial testing and showed no decline at retesting 2.35 years later. At that point, symptoms had been present for 6.26 years. Although memory preservation was observed in the PPA-AD group, language functions declined significantly over the same period.

A recent study worked to define homogenous and clinically meaningful phenotypes of multiple sclerosis (MS) to improve measures and definitions over traditional dichotomous classifications. Ultimately, after assessing 1212 patients, the study identified 5 cognitive phenotypes. Preserved cognition was observed in 235 patients (19.4%), mild-verbal memory/semantic fluency was seen in 362 patients (29.9%), mild-multidomain involvement in 236 patients (19.5%), severe-executive attention in 167 patients (13.8%). and severe-multidomain in 212 patients (17.5%). Study author Maria A. Rocca, MD, and colleagues wrote that “in this cross-sectional study, we propose a classification of cognitive functions in patients with MS that is based on the identification of distinct cognitive phenotypes.”

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