Compositions for use in treating parkinson's disease and related disorders
Inventors
Afonso, Nuno • Sousa, Sara • Vaz, Rita • Chapela, Diana • Côrte-Real, Sofia
Assignees
Laboratorio Medinfar Produtos Farmaceuticos Sa • Laboratorio Medinfar Produtos Farmaceuticos SA • Technophage Investigacao e Desenvolvimento em Biotecnologia SA • Lusomedicamenta SA
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10471025-B2
Publication Date
2019-11-12
Expiration Date
Abstract
The present invention relates to methods of treating and managing Parkinson's disease and related disorders. The methods especially find use in managing motor symptoms, including gait problems, particularly during advanced stages when effectiveness of standard medications wear off or side effects become problematic, as seen in Parkinson's disease, other disorders treated with dopaminergic agents, and other conditions associated with motor problems, such as aging or stroke. The treatment also may include disease-modifying effects, neuroprotection of, or neurorescue effects on neuronal cells in patients with Parkinson's disease and other neurodegenerative disorders. In particular, the invention relates to method of administering pharmaceutical compositions comprising effective amounts of tapentadol or a pharmaceutically acceptable salt or derivative thereof or, in other embodiments, stavudine or nabumetone, or a derivative thereof, for treating symptoms associated with Parkinson's disease, either as individual active agents, in combination with each other, or in combination with agents known to treat Parkinson's disease, such as the dopaminergic agent levodopa. The invention also relates to methods of preparing pharmaceutical compositions comprising effective amounts of tapentadol, stavudine, or nabumetone, or a derivative thereof, or further in combination with a dopaminergic agent, or derivative thereof, as well as to methods of using the pharmaceutical compositions in treating Parkinson's disease, related disorders, other conditions treated with dopaminergic agents, and other conditions with gait problems, for example by oral administration of the compositions.
Core Innovation
The invention relates to treating a side effect of levodopa or a derivative thereof in a subject suffering from Parkinson’s disease. The treatment comprises administering a pharmaceutical composition comprising tapentadol or a derivative thereof and a pharmaceutically acceptable carrier, while not comprising an opioid antagonist, and the treatment comprises a reduction in duration and/or frequency of an OFF period of the disease.
During said OFF periods, the treatment delays or reduces at least one manifestation selected from dyskinesia, dystonia, chorea, athetosis, motor fluctuation, postural abnormality, bradykinesia, freezing of gait, shaking, rigidity, slowness of movement, difficulty with walking and gait, autonomic dysfunction, or cognitive impairment. The disclosed subject population includes a stage of Parkinson’s disease that is advanced or less responsive to levodopa than an earlier stage.
The partial patent content further describes a zebrafish 6-OHDA Parkinson’s disease phenotypic screen using FDA/market-approved small molecules, and reports dose-response and LD50 results together with neurorescue outcomes. In this context, tapentadol is described as a strong candidate with an indicated therapeutic window and neuroprotective effects, including locomotor recovery, TH+ dopaminergic neuron rescue, and recovery of freezing-of-gait-related parameters.
Claims Coverage
Two independent claims are present. Both claims cover tapentadol-containing pharmaceutical compositions for levodopa-associated OFF periods in Parkinson’s disease, with reduction of OFF-period duration and/or frequency and delaying or reducing specified OFF-period manifestations; one independent claim further specifies a tapentadol hydrochloride daily dose range.
Tapentadol composition for reducing off periods
Administering a pharmaceutical composition comprising tapentadol or a derivative thereof and a pharmaceutically acceptable carrier, while not comprising an opioid antagonist, to treat a side effect of levodopa or a derivative thereof in a subject suffering from Parkinson’s disease, wherein treatment comprises a reduction in duration and/or frequency of an OFF period of the disease.
Delaying or reducing off-period manifestations with tapentadol
During said OFF periods, delaying or reducing at least one of dyskinesia, dystonia, chorea, athetosis, motor fluctuation, postural abnormality, bradykinesia, freezing of gait, shaking, rigidity, slowness of movement, difficulty with walking and gait, autonomic dysfunction, or cognitive impairment.
Tapentadol hydrochloride dose range for off periods
Administering a pharmaceutical composition to a subject suffering from Parkinson’s disease and having a side effect of OFF periods to levodopa therapy, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and tapentadol hydrochloride in an amount to provide an effective dose of about 100-250 mg/day, and wherein treatment comprises reducing duration and/or frequency of said OFF periods.
Off-period manifestation management in levodopa-treated subjects
Delaying or reducing during said OFF periods at least one of dyskinesia, dystonia, chorea, athetosis, motor fluctuation, postural abnormality, bradykinesia, freezing of gait, shaking, rigidity, slowness of movement, difficulty with walking and gait, autonomic dysfunction, or cognitive impairment.
Across both independent claims, the inventive coverage is directed to tapentadol-containing pharmaceutical compositions for levodopa-associated OFF periods in Parkinson’s disease, with reduction of OFF-period duration and/or frequency and delaying or reducing specified OFF-period manifestations; one independent claim specifies a tapentadol hydrochloride effective daily dose range of about 100-250 mg/day.
Stated Advantages
Reduction in duration and/or frequency of an OFF period of the disease.
Delaying or reducing at least one of dyskinesia, dystonia, chorea, athetosis, motor fluctuation, postural abnormality, bradykinesia, freezing of gait, shaking, rigidity, slowness of movement, difficulty with walking and gait, autonomic dysfunction, or cognitive impairment during OFF periods.
Neuroprotective effects and locomotor recovery with recovery of freezing-of-gait-related parameters in the zebrafish 6-OHDA Parkinson’s disease phenotypic screen.
TH+ dopaminergic neuron rescue.
Documented Applications
In vivo zebrafish 6-OHDA Parkinson’s disease phenotypic screening of FDA/market-approved small molecules, reporting neurorescue outcomes including locomotor recovery and TH+ dopaminergic neuron rescue.
Use of tapentadol in the described zebrafish screen as a strong candidate with an indicated therapeutic window and effects including recovery of freezing-of-gait parameters.
Treatment of Parkinson’s disease in subjects receiving levodopa therapy, specifically for OFF-period side effects and OFF-related motor and non-motor symptoms.
Interested in licensing this patent?