Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Feasibility for Individuals with Severe Spinal Muscular Atrophy II (S46.004)

Objective: NA Background: Outcome measure development for Spinal Muscular Atrophy (SMA) has focused on clinical trial readiness, and now exist across all SMA types. However, gross motor evaluation of older severely weak patients with SMA remains a challenge. The CHOP INTEND is a validated motor outcome measure developed for weak infants with type 1 SMA. Here we demonstrate its potential utility of a sub set of CHOP INTEND items for a series of individuals with type 2 SMA with scores on the Expanded Hammersmith Functional Motor Scale (HFMSE) of 2 or less. Design/Methods: We reviewed CHOP INTEND and HFMSE scores for 13 individuals (age 7–40) with type 2 SMA whose HFMSE scores were ≤2. The objective was to determine if the distribution of scores on subset of the CHOP INTEND was broader than the HFMSE scores, indicating enhanced sensitivity when administered in severe type 2 SMA. Qualitative review of difficulties experienced and clinical reasoning associated with testing non-infants was discussed among the physical therapists to determine themes. Results: Eight individuals scored 0 on the HFMSE and 5 scored 1 or 2 primarily reflecting minimal leg movement. The median CHOP INTEND score was 16.1 (IQR 10–22). Two patients were retested after their Spinraza loading doses and improved from 23 to 31 and from 27 to 29 while their HFMSE remained at 0. Items 11, 15, and 16 (requiring suspension) could not be tested in older individuals resulting in a score of 0. Conclusions: The CHOP INTEND may be more sensitive to changes in gross motor function and muscle strength in individuals with type 2 SMA due to a floor effect on HFMSE, and may be a reliable measure for long-term follow up. Longitudinal assessment to evaluate the sensitivity of a subset of the CHOP INTEND to detect change over time in weak SMA individuals is required. Disclosure: Dr. Kichula has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Avexis. Dr. Duong has nothing to disclose. Dr. Glanzman has nothing to disclose. Dr. Pasternak has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Scientific advisory board for Avexis Pharmaceuticals. Dr. Darras has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Darras has served as an ad hoc scientific advisory board member for AveXis, Biogen, Cytokinetics, Marathon Pharmaceuticals, PTC Therapeutics, Roche, and Sarepta; and has been an advisor for Bristol-Myers Squibb and Ionis Pharmaceuticals, Inc.; he has. Dr. Darras has received research support from Dr. Darras has received research support from from Ionis Pharmaceuticals, Inc. for the ENDEAR, CHERISH, CS2/CS12 studies, from Biogen for CS11 , as well as from Cytokinetics, PTC Therapeutics, Fibrogen and Summit. Dr. Finkel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees and travel costs from AveXis, Biogen, Catabasis, Ionis, Mitobridge, and Summit. Dr. Finkel has received research support from My institution received research support to perform clinical trials from Biogen, BMS, Catabasis, Cytokinetics, Ionis, Lilly, ReveraGen, Sarepta, and Summit. Dr. De Vivo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting/Advisory Board membership with AveXis, Biogen, Sarepta, PTC, Cytokinetics, Ultragenyx, and Sanofi. Dr. De Vivo has received research support from Clinical trials support from Sarepta, PTC, Ultragenyx, and Biogen, animal model licensing to Sanofi. Dr. Zolkipli-Cunningham has nothing to disclose. Dr. Day has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AMO, Audentes, AveXis, Biogen, Cytokinetics, Pfizer, Santhera, Sarepta.