阅读说明：本技术 治疗不宁腿综合征的治疗剂 (Therapeutic agent for treating restless leg syndrome ) 是由 M·法克拓尔 M·施特鲁普 于 2019-02-14 设计创作，主要内容包括：本公开提供了不宁腿综合征(RLS)或与RLS相关的一种或多种症状的治疗,所述治疗包括施用亮氨酸、乙酰-亮氨酸或其药学上可接受的盐。(The present disclosure provides for the treatment of Restless Leg Syndrome (RLS) or one or more symptoms associated with RLS comprising the administration of leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof.)

1. Leucine, acetyl-leucine, or a pharmaceutically acceptable salt thereof, for use in a method of treating Restless Leg Syndrome (RLS) or one or more symptoms associated with RLS in a subject in need thereof.

2. Leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof for use in a method according to claim 1, wherein the RLS is primary RLS.

3. Leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof for use in a method according to claim 1, wherein the RLS is a secondary RLS.

4. Leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof for use in a method according to claim 1, wherein the method comprises administering to the subject a therapeutically effective amount of leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof.

5. The leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof for use in a method of claim 4, wherein said administering is performed over time and the subject's International restless leg syndrome score Scale (IRLS) is reduced by at least 10% after said administering compared to baseline.

6. The leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof for use in a method of claim 5, wherein the subject's International restless leg syndrome score Scale (IRLS) is reduced by at least 50% after said administration as compared to the baseline.

7. Leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof for use in a method according to any one of claims 1 to 6, wherein the leucine is DL-leucine or the acetyl-leucine is acetyl-DL-leucine.

8. Leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof for use in a method according to any one of claims 1 to 6, wherein the leucine or acetyl-leucine has an enantiomeric excess of the L-enantiomer or the D-enantiomer.

9. The leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof for use in a method of any one of claims 1 to 8, wherein the method comprises administering the acetyl-leucine in a therapeutically effective amount of about 1g to about 15g per day, about 1g to about 10g per day, about 1.5g to about 7g per day, about 4g to about 6g per day, or about 4g to about 5g per day to a subject in need thereof.

10. A method for reducing, inhibiting or eliminating one or more symptoms of Restless Leg Syndrome (RLS) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of leucine, acetyl-leucine or a pharmaceutically acceptable salt thereof.

11. The method of claim 10, wherein the one or more symptoms are selected from the group consisting of calf sensation, periodic leg movements in sleep, unpleasant leg sensations, motor impulsion, restlessness, daytime sleepiness, and sleep disorders.

12. The method of claim 10 or 11, wherein the leucine is DL-leucine or the acetyl-leucine is acetyl-DL-leucine.

13. The method of claim 10 or 11, wherein the leucine or acetyl-leucine has an enantiomeric excess of the L-enantiomer or the D-enantiomer.

14. The method of any one of claims 10 to 13, wherein the therapeutically effective amount is about 1g to about 15g per day, about 1g to about 10g per day, about 1.5g to about 7g per day, about 4g to about 6g per day, or about 4g to about 5g per day.

Examples

Patient 1 the patient in this study was a 55 year old female who showed weakness in the proximal extremities. This patient had a slow progression of head flexor paralysis since age 42 and was diagnosed (genetically confirmed) with myotonic dystrophy type 2. After consultation at age 55, the patient reported no sensory symptoms, but rather restless leg syndrome appeared during the last two years during night and day rest. Pre-treatment with dopamine agonists is asymptomatic. The serum creatine kinase activity is only slightly increased and reaches 400 IU/L. Patients were evaluated using the RLS diagnostic index (RLS-DI) (see Walters et al, Sleep Med 2003; 4(2): 121;. 132;). The patient had an international restless leg syndrome score scale score (IRLS) of 36 points and was therefore diagnosed with severe RLS. The patient began to receive therapy with acetyl-DL-leucine at a dose of 3g per day for the first week and 5g per day for the second week. IRLS decreased to 26 within 14 days of administration of acetyl-DL-leucine and to 9 after a further 5 weeks. Treatment was discontinued 4 weeks after 12 weeks of treatment and IRLS rose to 28 weeks. After 2 weeks of treatment restart, the score again dropped to 8. The IRLS score stabilized at 8 points for longer than 22 weeks of continuous treatment.

Patient 2

The patient in this study was a 72 year old female who showed weakness in the proximal extremities. This patient had a slow progression of head flexor paralysis since age 48 and was diagnosed (genetically confirmed) with myotonic dystrophy type 2 by 15 years ago. After a consultation at 72 years of age, the patient reported no sensory symptoms, but rather restless leg syndrome appeared during the last eight years during night and day breaks. Pre-treatment with dopamine agonists, levodopa, pregabalin and opioids did not have sustained symptomatic relief. The serum creatine kinase activity is slightly increased and is 300 IU/L. Iron measurements and all additional laboratory investigations were normal. Patients were evaluated using RLS-DI and were diagnosed with moderate to severe RLS because of an IRLS of 32. The patient began to receive therapy with acetyl-DL-leucine at a dose of 3g per day for the first week and 5g per day for the second week. Within 14 days of administration of acetyl-DL-leucine, IRLS decreased to 22 and after another 5 weeks, IRLS decreased to 7. The IRLS score stabilized at 8 points for longer than 28 weeks of continuous treatment.

Patient 3

The patient in this case study was a 73 year old male with mild proximal weakness of the upper and lower extremities occurring from age 50 and progressing slowly. The patient was diagnosed (genetically confirmed) with mcardel's myopathy about 16 years ago. After consultation at the age of 73 years, the patient reported no sensory symptoms, but complained of severe fatigue and decreased endurance. The patient further reported restless leg syndrome that occurred during night and day rest in the last 12 years. Pre-treatment with dopamine agonists, levodopa, pregabalin, did not result in sustained symptomatic relief. The serum creatine kinase activity is slightly increased and is 200 IU/L; however, patients had 5 rhabdomyolytic events over the past 20 years. Repeated iron measurements and all additional laboratory investigations were normal. Patients were evaluated using RLS-DI and were diagnosed with severe RLS as the IRLS was 34. The patient began to receive therapy with acetyl-DL-leucine at a dose of 3g per day for the first week and 5g per day for the second week. IRLS decreased to 20 within 21 days of administration of acetyl-DL-leucine and to 10 after another 10 weeks. The IRLS score stabilized at 10 points for more than 30 weeks of continuous treatment. In addition, the patient's fatigue level decreased from 53 points to 28 points (fatigue severity scale: 9 points (minimum) to 63 points (maximum)).

Patient 4

The patient in this case study was a 59 year old female, presenting with symptoms of RLS, accompanied by RLS of unknown etiology. After consultation at 59 years of age, the patient reported no sensory symptoms, but had restless leg syndrome during night and day rest for at least the past 15 years. Pre-treatment with dopamine agonists, levodopa, pregabalin, had no sustained relief. Iron measurements and all additional laboratory investigations were normal. Patients were evaluated using RLS-DI and were diagnosed with moderate to severe RLS because of an IRLS of 32. The patient began to receive therapy with acetyl-DL-leucine at a dose of 3g per day for the first week and 5g per day for the second week. IRLS decreased to 8 within 14 days of administration of acetyl-DL-leucine and to 6 after 2 weeks. The IRLS score stabilized at 6 points for longer than 4 weeks of continuous treatment.