IB1000s Series Publications

Mode of Action

IB1000s are a series of orally administered, modified amino-acid analogs/esters that are well tolerated and have established safety profiles.

IB1000s are believed to have an effect on the normalization of neuronal membrane potential and intracellular ion regulation via calcium channels, and have been observed to have symptomatic and neuroprotective properties and disease-modifying potential.

To date, IntraBio, with its collaborators, has evaluated the effect of IB1000s in compassionate-use studies in over 100 patients. These studies form the scientific basis for IB1000s to be further investigated for the treatment of 18 indications, including Traumatic Brain Injury (TBI) Lewy Body Dementia (LBD), Restless Leg Syndrome (RLS),  and Amyotrophic Lateral Sclerosis (ALS), all of which of have high-unmet medical needs.

Several publications have explored the mechanism of action of IB1000 in different model systems, listed below along with the published observational clinical study outcomes. In addition, there are several peer-reviewed papers that quantify the efficacy of IB1000 in the treatment of neurodegenerative diseases.

NON-CLINICAL STUDIES

Title
Author(s)
Summary
Günther L, Beck R, Xiong G, Potschka H, Jahn K, Bartenstein P, Brandt T, Dutia M, Dieterich M, Strupp M, la Fougère C, Zwergal A.

PLoS One. 2015 Mar 24;10(3):e0120891. doi: 10.1371/journal.pone.0120891. eCollection 2015. PMID: 25803613

Feil K, Bremova T, Muth C, Schniepp R, Teufel J, Strupp M.

Cerebellum.15(1):38-42. (2016).

Kalla, R., Teufel, J., Feil, K., Strupp, M.

Journal of Neurology 263 (2016).

Churchill C., Strupp M., Galione A., Platt F.

bioRxiv, 2019. https://doi.org/10.1101/738286

Sarkar, C., Hegdekar, N., Lipinski, M.M

bioRxiv, 2019. https://doi.org/10.1101/759894

Treatment with N-acetyl-L-leucine is expected to be beneficial in restricting neuronal death and hence improving neurological function after Traumatic Brain Injury (TBI) and is a promising, novel, neuroprotective drug candidate for the treatment of TBI.

CLINICAL STUDIES

Title
Author(s)
Summary
Ferber-Viart C, Dubreuil C, Vidal PP. Audiol Neurootol.

2009;14(1):17-25. doi: 10.1159/000148206. Epub 2008 Jul 29. PMID: 18663295
Acetyl-DL-leucine improves gait variability in patients with cerebellar ataxia—a case series Schniepp et al. Cerebellum & Ataxias (2016) 3:8 DOI 10.1186/s40673-016-0046-2
Gait ataxia in humans: vestibular and cerebellar control of dynamic stability J Neurol (2017) 264 (Suppl 1):S87–S92 DOI 10.1007/s00415-017-8482-3

Bremova T, Malinová V, Amraoui Y, Mengel E, Reinke J, Kolníková M, Strupp M.

Demonstrates that Acetyl-DL-Leucine treatment is associated with improvements in ataxia and quality of life in patients with Niemann-Pick Disease Type C.Neurology 85, 1368-1375 (2015).

Strupp M, Teufel J, Habs M, Feuerecker R, Muth C, van de Warrenburg BP, Klopstock T, Feil K.

A paper exhibiting the significant benefit of Acetyl-DL-Leucine in the treatment of patients with cerebellar ataxia.Journal of Neurology 260, 2556-2561 (2013).

Schniepp, R., Strupp, M. Wuehr, M. Jahn, K. Dieterich, M. Brandt, T. Feil, K.

A paper exhibiting the significant benefit of Acetyl-DL-Leucine in the treatment of Gait variability in patients with cerebellar ataxia. Cerebellum & Ataxias 3:8 (2016).

Platt, F., Strupp, M.

A case study demonstrating that, in addition to being of benefit in patients with cerebellar ataxia and Niemann-Pick disease type C, acetyl-DL-leucine can increase mobility and quality of life in a healthy elderly subject.Journal of Neurology 263, 1239-40 (2016).

Cortina-Borja,M., te Vruchte,D., Mengel,E., Amraoui,Y., Imrie, J. ,Jones,S., Dali,C., Fineran,P., Kirkegaard,T., Runz,H., Lachmann,R., Bremova-Ertl,T., Strupp,M., Platt,F.

Demonstrates the annual severity increment score (ASIS) has prognostic value in assessing the progression of Niemann-Pick type C, and that long-term treatment with N-Acetyl-DL-leucine is associated with a reduction in ASIS scores. Orphanet Journal of Rare Diseases 13, 1-16 (2018).

Strupp, M., Bayer, O., Feil, K., Straube, A.

A paper demonstrating the significant benefit of N-Acetyl-DL-Leucine for the prophylactic treatment of migraine, as well as migraine with aura. Journal of Neurology.