Recombinant botulinum toxin with improved safety and effectiveness for treatment of dystonia

Ended Project Grant Awarded Last action

Award ID
R43NS122661
Recipient
Awarding agency
Obligated
$553,231

Award facts

Completion date
Place of performance
New York, NY 10027, USA

Award details come from USAspending.gov.

Description

Abstract
Botulinum neurotoxin (BONT) is the most toxic protein known to science. IT is also the active ingredient in ® pharmaceutical products like botox (ALLERGAN), which have proven safe and effective for multiple neuromuscular indications. All current BONT products are manufactured from clostridium botulinum cultures and have similar safety characteristics, which include limitations on dosing and a black box warning in labeling. Because of its inherent toxicity and narrow therapeutic window, optimal clinical outcomes are difficult to achieve in indications involving large muscle groups, such as cervical dystonia, post-stroke spasticity and pediatric cerebral palsy. Though improved muscle tone can clearly be achieved, clinicians tend to dose on the side of caution, and overall clinical outcomes leave significant room for improvement. We here propose building on data generated with a previous candidate for a "safer BONT" pharmaceutical (sbir phase 1 1R41NS086115-01A1) which found that specific amino acid substitutions to BONT/A1 can produce a recombinant BONT/A1 with an improved safety margin compared to WT BONT/A1, (US 8,865,186). The initial lead candidate designed and tested, cyto-012, had an improved safety margin, but its absolute potency was such that doses required for efficacy were also immunogenic. Here, we propose testing a new recombinant BONT/A1 derivative termed cyto-014, designed to have potency and immunogenicity similar to WT BONT/A1, while retaining the desired improvement in safety suggested by our preliminary studies. This proposal is intended to compare the dose-response behavior, safety margin and maximum tolerated dose of cyto-014 relative to WT BONT/A1 in appropriately powered studies, and to evaluate its immunogenicity and effectiveness for repeat treatment. Successful completion of the proposed studies will support a phase II study to focus on pre-clinical development activities aimed at filing an IND.

Transactions

Action Obligated Date
Amendment $0
Amendment $138,307
Amendment $138,307
Original award $276,617

Quick answers

Who received award R43NS122661?

R43NS122661 was awarded to Cytodel, Inc. by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on March 1, 2022.

How much is award R43NS122661 worth?

$553,231 has been obligated on R43NS122661.

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