{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:38:13Z","timestamp":1785523093613,"version":"3.56.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008967","name":"Philipps-Universit\u00e4t Marburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008967","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Multiple system atrophy (MSA) is a rare, rapidly progressive alpha-synucleinopathy characterized by autonomic dysfunction, parkinsonism and marked cerebellar ataxia, with very limited treatment options. N-acetyl-DL-leucine (ADLL) (Tanganil\u2122), a racemic derivative of leucine is usually well tolerated and has shown promise in improving cerebellar symptoms and reducing REM sleep behavior disorder (RBD), a common non-motor dream-sleep disorder feature of alpha-synucleinopathy. Given this dual potential, we treated three patients with advanced-stage MSA under compassionate use rules.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentations<\/jats:title>\n            <jats:p>Three patients with advanced-stage MSA and severe cerebellar symptoms\u2014two of whom also had moderate RBD\u2014were treated with ADLL (Tanganil<jats:sup>TM<\/jats:sup>), titrated to 5g\/day over 10 days. While both patients with RBD reported self-assessed decrease of RBD symptoms within 2\u20133 weeks on the full dosage (approximately four weeks after treatment initiation), all three patients had major worsening of gait and balance during the same period, leading to sudden falls and overall health decline. These adverse events prompted early discontinuation of therapy. Gait improved within two weeks after discontinuation of therapy in two patients. In parallel, the RBD phenotype reoccurred. In the third, who had very advanced MSA and concurrent infections, gait only slowly improved over time and it remains unclear whether his worsening of truncal ataxia was attributable to ADLL (Tanganil<jats:sup>TM<\/jats:sup>), or whether it was related to his concurrent infections with slow recovery.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>While ADLL improved RBD, it was poorly tolerated in these three patients with advanced-stage MSA of predominantly cerebellar type. Further studies are needed to evaluate its safety and efficacy in different, preferably early, stages of MSA.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12883-025-04451-7","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T09:18:22Z","timestamp":1759396702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Acetyl-DL-leucine (Tanganil\u2122) in three patients with advanced multiple system atrophy"],"prefix":"10.1186","volume":"25","author":[{"given":"Wolfgang H.","family":"Oertel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin T.","family":"Henrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Sittig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp T.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Strupp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Janzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanni F.","family":"Geibl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Ruppert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"issue":"6","key":"4451_CR1","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1002\/mds.29005","volume":"37","author":"GK Wenning","year":"2022","unstructured":"Wenning GK, Stankovic I, Vignatelli L, Fanciulli A, Calandra-Buonaura G, Seppi K, et al. 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No formal ethical approval was required, as this report describes the treatment of three individual patients under compassionate use (\u201cHeilversuch\u201d) with Acetyl-DL-Leucine (Tanganil\u2122), outside of a clinical trial (clinical trial number: not applicable). Written informed consent was obtained from all three patients for the compassionate off-label use of ADLL, for clinical follow-up to evaluate its safety and efficacy, and for publication of their case descriptions.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent for publication was obtained from all three patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"This case observational study in three patients has been conducted with the drug TanganilTM. This drug contains the racemate Acetyl-DL-Leucine, i.e. to equal parts the bio-inactive substance Acetyl-D-Leucine and the bioactive enantiomer Acetyl-L-Leucine. This drug is produced by the company Pierre Fabre, Medicaments, France and approved for the indication vertigo in France. The company Pierre Fabre was not aware of our observational study as none of the authors had any contact during and after the conduct of the study with the company.Wolfgang Oertel (WO) and Michael Strupp (MS) are members of the scientific advisory board of the company IntraBio. WO holds stock options of the company IntraBio, whereas MS is an investor and shareholder of the company Intrabio. In addition, we declare that neither the company Pierre Fabre nor the company IntraBio have supported the conduct of the case report submitted with this article by any means.Wolfgang H. Oertel also acts as a consultant for the company MODAG. He holds stock options with MODAG unrelated to this work. Elisabeth Sittig has no conflict of interest to declare. Philipp T. Meyer has no conflict of interest to declare. Fanni F. Geibl has no conflict of interest to declare. Martin T. Henrich has no conflict of interest to declare. Elisabeth Ruppert has no conflict of interest to declare. Michael Strupp is Joint Chief Editor of the Journal of Neurology, Editor in Chief of Frontiers Neuro-otology and Section Editor of F1000. He acts as a consultant for Abbott, AurisMedical, Bulbitec, Heel, Sensorion and Vertify. The institution of M.S., not M.S. personally received\/s support for clinical studies from Decibel, U.S.A., Cure within Reach, U.S.A. and Heel, Germany.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"407"}}