A perspective on In vitro developmental neurotoxicity test assay results: An expert panel review.

For decades, there has been increasing concern about the potential developmental neurotoxicity (DNT) associated with chemicals. Regulatory agencies have historically utilized standardized in vivo testing to evaluate DNT. Owing to considerations including higher-throughput screening for DNT, reduction in animal use, and potential cost efficiencies, the development of alternative new approach methods (NAMs) occurred; specifically, the advent of the DNT in vitro test battery (DNT IVB). SciPinion convened an expert panel to address specific questions related to the interpretation of in vitro DNT test data. The consensus of the expert panel was that the DNT IVB might be used during initial screening, but it is not presently a complete or surrogate approach to determine whether a chemical is a DNT in humans. By itself, the DNT IVB does not have the ability to capture nuances and complexity of the developing nervous system and associated outcomes including behavioral ontogeny, motor activity, sensory function, and learning/memory. Presently, such developmental landmarks cannot be adequately assessed in the DNT IVB or by other NAMs. The expert panel (all who serve as co-authors of this review) recommended that additional data generation and validation is required before the DNT IVB can be considered for application within global regulatory frameworks for decision-making.

Effects of dalfampridine on multi-dimensional aspects of gait and dexterity in multiple sclerosis among timed walk responders and non-responders.

BACKGROUND: Dalfampridine extended release 10mg tablets (D-ER) have demonstrated improvement in walking for ambulatory persons with multiple sclerosis (pwMS), termed "responders." OBJECTIVE: This study examined the extent additional aspects of gait and dexterity change for patients prescribed D-ER. METHODS: Over 14-weeks, walking endurance, dynamic gait, self-report walking ability and fine and gross dexterity were examined in pwMS prescribed D-ER as a part of routine clinical care. RESULTS: The final results (n=39) validate that a subset of pwMS improve walking speed (Time 25-Foot Walk Test, p<0.0001). Significant improvements in gait and dexterity were observed even among participants who did not improve walking speed. Improvements were evident in gait and dexterity domains including Six Minute Walk Test, p=0.007, Six-Spot Step Test, p<0.0001, Multiple Sclerosis Walking Scale-12, p<0.0001, Nine Hole Peg Test, p<0.0001 dominant and non-dominant sides, and Box and Blocks Test, p=0.005 and 0.002, dominant and non-dominant sides, respectively. CONCLUSIONS: These findings suggest that D-ER may be a potential treatment for gait impairments, beyond walking speed and dexterity in pwMS. Further investigation regarding D-ER response is warranted.