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Botulinum toxin type B (BoNT/B) has been recommended as an alternative for patients who have become resistant to botulinum toxin type A (BoNT/A). This study aimed to compare the clinical effect, within a patient, of four injections with low doses of rimabotulinumtoxinB with the effect of the preceding abobotulinumtoxinA (aboBoNT/A) injections. In 17 patients with cervical dystonia (CD) who had become resistant to aboBoNT/A, the clinical effect of the first four rimabotulinumtoxinB (rimaBoNT/B) injections was compared to the effect of the first four aboBoNT/A injections using a global assessment scale and the TSUI score. After the first two BoNT/B injections, all 17 patients responded well and to a similar extent as to the first two BoNT/A injections, but with more side effects such as dry mouth and constipation. After the next BoNT/B injection, the improvement started to decline. The response to the fourth BoNT/B injection was significant (p < 0.048) lower than the fourth BoNT/A injection. Only three patients developed a complete secondary treatment failure (CSTF) and five patients a partial secondary treatment failure (PSTF) after four BoNT/B injections. In nine patients, the usual response persisted. With the use of low rimaBoNT/B doses, the induction of CSTF and PSTF to BoNT/B could not be avoided but was delayed in comparison to the use of higher doses. In contrast to aboBoNT/A injections, PSTF and CSTF occurred much earlier, although low doses of rimaBoNT/B had been applied.

To improve the pharmacological properties of maize ribosome-inactivating protein (maize RIP) for targeting HIV-infected cells, the previously engineered TAT-fused active form of maize RIP (MOD) was further engineered for cysteine-directed PEGylation. In this work, two potential antigenic sites, namely Lys-78 and Lys-264, were identified. They were mutated to cysteine residue and conjugated with PEG5k or PEG20k. The resultant PEG derivatives of MOD variants were examined for ribosome-inactivating activity, circulating half-life and immunogenicity. Our results showed that MOD-PEG conjugates had two- to five-fold lower biological activity compared to the wild-type. Mutation of the two sites respectively did not decrease the anti-MOD IgG and IgE level in mice, but the conjugation of PEG did dramatically reduce the antigenicity. Furthermore, pharmacokinetics studies demonstrated that attachment of PEG20k prolonged the plasma half-life by five-fold for MOD-K78C and 17-fold for MOD-K264C, respectively. The site-specific mutation together with PEGylation therefore generated MOD derivatives with improved pharmacological properties. [ABSTRACT FROM AUTHOR]

Botulinum toxin type B (BoNT/B) has been recommended as an alternative for patients who have become resistant to botulinum toxin type A (BoNT/A). This study aimed to compare the clinical effect, within a patient, of four injections with low doses of rimabotulinumtoxinB with the effect of the preceding abobotulinumtoxinA (aboBoNT/A) injections. In 17 patients with cervical dystonia (CD) who had become resistant to aboBoNT/A, the clinical effect of the first four rimabotulinumtoxinB (rimaBoNT/B) injections was compared to the effect of the first four aboBoNT/A injections using a global assessment scale and the TSUI score. After the first two BoNT/B injections, all 17 patients responded well and to a similar extent as to the first two BoNT/A injections, but with more side effects such as dry mouth and constipation. After the next BoNT/B injection, the improvement started to decline. The response to the fourth BoNT/B injection was significant (p < 0.048) lower than the fourth BoNT/A injection. Only three patients developed a complete secondary treatment failure (CSTF) and five patients a partial secondary treatment failure (PSTF) after four BoNT/B injections. In nine patients, the usual response persisted. With the use of low rimaBoNT/B doses, the induction of CSTF and PSTF to BoNT/B could not be avoided but was delayed in comparison to the use of higher doses. In contrast to aboBoNT/A injections, PSTF and CSTF occurred much earlier, although low doses of rimaBoNT/B had been applied. [ABSTRACT FROM AUTHOR]

To improve the pharmacological properties of maize ribosome-inactivating protein (maize RIP) for targeting HIV-infected cells, the previously engineered TAT-fused active form of maize RIP (MOD) was further engineered for cysteine-directed PEGylation. In this work, two potential antigenic sites, namely Lys-78 and Lys-264, were identified. They were mutated to cysteine residue and conjugated with PEG 5k or PEG 20k . The resultant PEG derivatives of MOD variants were examined for ribosome-inactivating activity, circulating half-life and immunogenicity. Our results showed that MOD-PEG conjugates had two- to five-fold lower biological activity compared to the wild-type. Mutation of the two sites respectively did not decrease the anti-MOD IgG and IgE level in mice, but the conjugation of PEG did dramatically reduce the antigenicity. Furthermore, pharmacokinetics studies demonstrated that attachment of PEG 20k prolonged the plasma half-life by five-fold for MOD-K78C and 17-fold for MOD-K264C, respectively. The site-specific mutation together with PEGylation therefore generated MOD derivatives with improved pharmacological properties., Competing Interests: The authors declare no conflict of interest.