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Uses of myostatin antagonists, combinations containing them and uses thereof

a technology of myostatin and activin, which is applied in the field of activin type ii (actrii) receptor inhibitors, can solve the problems of cisplatin precipitating body and muscle weight loss, and achieve the effect of preventing the formation of apoptosis

Inactive Publication Date: 2022-08-25
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present patent is about a new type of mouse antibody called bimagrumab that can inhibit the action of a protein called myostatin, which plays a role in the growth of muscle cells. The patent evaluates the effect of bimagrumab in a mouse colon cancer model and shows that it can protect against cancer-induced cachexia (a condition that causes weight loss and muscle atrophy in cancer patients). The patent also discusses the advantages of using bimagrumab as a therapeutic approach compared to other methods of reducing myostatin activity. Overall, the patent shows the potential of bimagrumab as a promising treatment for cancer-related cachexia.

Problems solved by technology

Problematically, cisplatin has been shown to precipitate body and muscle weight loss as a side effect.

Method used

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  • Uses of myostatin antagonists, combinations containing them and uses thereof
  • Uses of myostatin antagonists, combinations containing them and uses thereof
  • Uses of myostatin antagonists, combinations containing them and uses thereof

Examples

Experimental program
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Effect test

example 1

Bimagrumab Prevents Cisplatin-Induced Body Weight Loss

[0163]Extensive body weight loss has emerged as a key determinant of cancer-related death. Thus longitudinally body weight development was monitored (FIGS. 1A and B). Ten days after starting the treatment, tumor-bearing animals receiving cisplatin as a mono-therapy had lost 20% of their initial body weight (FIGS. 1B and C). By contrast, vehicle-treated, tumor-bearing animals experienced a body weight decrease of 10%, while animals treated with CDD866 alone or in combination with cisplatin exhibited moderate body weight losses of only 3 and 5%, respectively (FIGS. 1B and C). In healthy control animals, cisplatin did not affect body weight and CDD866 administration resulted in a marked body weight gain in the absence and presence of cisplatin (FIGS. 1A and C). These data demonstrate that cisplatin, at an effective anti-tumor dose (cf. FIG. 1E), indeed precipitated body weight loss in cachectic animals and that CDD866 significantly ...

example 2

Bimagrumab Antagonizes Cisplatin-Induced Muscle Wasting

[0165]Given the positive effect of CDD866 on body weight, we next determined the impact of the various interventions on individual skeletal muscles. In gastrocnemius, cisplatin provoked a muscle weight loss of 25%. CDD866 treatment tended to reduce muscle weight loss to 13% and this protective effect was preserved in the presence of cisplatin (12%) (FIG. 2B). A similar level of protection was observed in quadriceps muscle (FIG. 2C). Tibialis anterior benefited most from CDD866 treatment. In tibialis anterior, cisplatin-treated animals experienced a muscle wasting of 34% and co-administration of CDD866 reduced muscle loss significantly to 16% (FIG. 2A).

example 3

Bimagrumab in Combination with Cisplatin Delays Time to Progression in Cancer Cachexia

[0166]Extensive tumor growth and subsequent body weight loss are important predictors of mortality in cancer patients. We therefore wanted to evaluate whether the combination of CDD866 and cisplatin has an impact on the length of survival. For ethical reason we abstained from classical survival studies. Instead, each mouse was individually euthanized when experiencing either a body weight loss exceeding 20% of initial body weight, or reaching a tumor volume of 1,500 mm3, determined as time-to-progression.

[0167]On average, animals receiving vehicle or cisplatin had to be sacrificed after 12 and 12 days, respectively (FIGS. 2D and E). CDD866 treated animals had to be euthanized after 16 days, which corroborates previous findings that CDD866 treatment reduced body weight loss, but did not promote tumor growth. The combined treatment of CDD866 and cisplatin was superior to any other intervention tested...

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PUM

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Abstract

The present invention relates to myostatin antagonists, for the treatment of cancer cachexia, and cancer cachexia due to chemotherapeutic treatment Especially, the myostatin antagonist bimagrumab was found to be beneficial in the treatment of cancer cachexia by reducing body weight loss. The present invention also relates to combinations and uses of a myostatin antagonist and an mTOR inhibitor for treating cancer cachexia by reducing, maintaining or increasing body weight loss or for use in treating age-related conditions.

Description

FIELD OF THE INVENTION[0001]The present disclosure relates to the use of myostatin or activin antagonists and in particular of activin type II (ActRII) receptor inhibitors in the treatment of cancer cachexia.[0002]The invention relates more specifically to combinations comprising (a) an activin type II receptor (ActRII) inhibitor and (b) a chemotherapeutic agent or a pharmaceutically acceptable salt thereof, for simultaneous, separate or sequential use, uses thereof, or methods of treatment using it, in the treatment of cancer cachexia.[0003]The disclosure also relates to combinations uses thereof of a myostatin antagonist and an mTOR inhibitor. Such a combined uses are for use in cancer cachexia and for age-related conditions.BACKGROUND OF THE INVENTION[0004]Cachexia affects the majority of patients with advanced cancer and is associated with a poor outcome, a reduction in treatment tolerance, response to therapy, quality of life and duration of survival. Skeletal muscle loss appea...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61P21/00A61P35/00A61K33/243A61K31/436
CPCA61K39/3955A61P21/00A61P35/00A61K33/243A61K31/436A61K31/282A61P11/00A61P13/08A61P13/12A61P15/10A61P17/00A61P19/02A61P19/08A61P19/10A61P25/00A61P25/14A61P25/28A61P27/02A61P27/12A61P27/16A61P3/00A61P3/02A61P3/04A61P37/04A61P43/00A61P9/00A61P9/04A61P9/10A61P9/12A61P3/10A61K2300/00
Inventor HATAKEYAMA, SHINJIROUBENOFF, RONENNTRIFILIEFF, ESTELLEFEIGE, JEROMEKLICKSTEIN, LLOYD B.
Owner NOVARTIS AG
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