2021-2025 Research Papers
This is where we will share the latest scientific papers on all things NA.
Proceedings of the 12th International Meeting on Neuroacanthocytosis, Cohen Syndrome, and Other VPS13-Related Disorders
January 2026
Neuropathological Characterisation of McLeod Syndrome With a Proposed New Grading System
October 2025
The Diverse Neuromuscular Spectrum of VPS13A Disease
October 2025
Impaired hematopoiesis and embryonic lethality at midgestation of mice lacking both lipid transfer proteins VPS13A and VPS13C
September 2025
Copyright: © 2025 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
For full text: https://pubmed.ncbi.nlm.nih.gov/40956846/
Various Gait Patterns in Chorea-Acanthocytosis
July 2025
No abstract available
Neurodegenerative and Neurodevelopmental Roles for Bulk Lipid Transporters VPS13A and BLTP2
March 2025
Red blood cell lipid distribution in the pathophysiology and laboratory evaluation of chorea-acanthocytosis and McLeod syndrome patients
March 2025
Phosphatidylethanolamines are the Main Lipid Class Altered in Red Blood Cells from Patients with VPS13A Disease/Chorea-Acanthocytosis
December 2024
Exploring the pathophysiological mechanisms and wet biomarkers of VPS13A disease
November 2024
The protean presentations of XK disease (McLeod syndrome): a case series with new observations and updates on previously reported families
September 2024
Systematic review of phenotypes in McLeod syndrome and case report of a progressive supranuclear palsy in a female carrier
August 2024
A case of chorea-acanthocytosis with significant improvement of symptoms at one year with deep brain stimulation: case report and literature review
July 2024
Polysomnographic findings in the ultra-rare McLeod syndrome: further documentation of sleep apnea as a possible feature
March 2024
Erythroid Differentiation Dependent Interaction of VPS13A with XK at the Plasma Membrane of K562 Cells
January - December 2023
Neuroacanthocytosis Syndromes: The Clinical Perspective
January - December 2023
Proceedings of the Eleventh International Meeting on Neuroacanthocytosis Syndromes
November 2023
VPS13A knockdown impairs corticostriatal synaptic plasticity and locomotor behavior in a new mouse model of chorea-acanthocytosis
October 2023
A Case of McLeod's Syndrome Presenting with Severe Decompensated Heart Failure
September 2023
of MLS, which was managed with guideline-directed medical therapy and placement of an implantable cardioverter defibrillator with recovery in ejection fraction.
Authors: Hemanth K. Boppana, MD, Samarthkumar Thakkar, MD, Harsh P. Patel, MD, Rody G. Bou Chaaya, MD, Scott Feitell, DO
Sphingolipid and Phospholipid Levels Are Altered in Human Brain in Chorea-Acanthocytosis
June 2023
Sleep Disorders in McLeod Syndrome
For a limited time (October 3, 2022), we have full access to this article published in the journal Parkinsonism and Related Disorders via this link:
Neuropathology of McLeod Syndrome
December 2021
Background. McLeod syndrome (MLS) is a rare (prevalence: <1/100,000), slowly progressive, X-linked recessive subtype
of neuroacanthocytosis with mean age at onset of 47 years. Penetrance is high and may be complete after age 60 years. Individuals with MLS show an Xp21-linked Kell blood group variant (depressed Kell erythrocyte antigens including the erythrocyte membrane protein Kx) caused by an XK gene mutation. Neurological features include chorea, involuntary tongue
movements, dysarthria, dysphagia, dystonia, motor/vocal tics, cognitive impairment, neuropsychological disturbances (attention, memory, frontal lobe deficits), axonal sensorimotor neuropathy, myopathy, seizures, and biting of lips/tongue.
Cardiac manifestations and hepatosplenomegaly occur.
We describe two male siblings (61 and 63 years old) who presented with generalized chorea since their early twenties, sensory loss, areflexia, depression, anxiety, seizures, mild personality changes, and, since their mid-40s, cognitive impairment. Distal muscle weakness occurred in the older brother. Acanthocytes were detected. The XK mutation IVS2-2A>G was identified (younger brother).
Authors: Deutschländer, Angela B., Dickson, Dennis W., Wszolek, Zbigniew K. Neuropathology of McLeod Syndrome. Movement Disorders. 2021. https://doi.org/10.1002/mds.28882
[if you have a problem accessing the full article, write joy@naadvocacyusa.org and request a PDF.]
Three new XK alleles; two associated with a McLeod RBC phenotype
September 2021
Background. The Kx antigen is the product of the XK gene on the X chro- mosome and the only known antigen in the XK blood group system.1 The Kx and Kell proteins are covalently linked on the red blood cells (RBC) membrane, and changes in the XK gene that abolish expression of Kx antigen are associated with very weak expression of Kell system antigens, known as the McLeod phenotype, found almost exclusively in males. The phenotype may be fortuitously detected when screening healthy blood donors.2 Importantly, XK null and missense mutations can cause the McLeod syndrome which is associated with acanthocytes, a late onset of neurological impairment, chorea-like disease, cardiomyopathy, and various degrees of muscular atrophy.1,3 Large deletions in the X chromosome can also cause McLeod syndrome, X-linked Chronic Granulomatous Disorder, and the contiguous gene deletion syndrome.4,5 Here, we report the molecular basis of the McLeod phenotype in a healthy male blood donor found by random screening for depressed Kell expression, a patient referred for a family history of a McLeod phenotype, and a patient referred for testing as part of a neurological workup.
Authors: Floch A, Lomas-Francis C, Vege S, Westhoff CM. Three new XK alleles; two associated with a McLeod RBC
phenotype. Transfusion. 2021;1–2. https://doi.org/ 10.1111/trf.16650
[if you have a problem accessing the full article, write joy@naadvocacyusa.org and request a PDF.]
Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis
May 2021
Abstract. Chorea-Acanthocytosis (ChAc) is a devastating, little understood, and currently untreatable neurodegenerative disease caused by VPS13A mutations. Based on our recent demonstration that accumulation of activated Lyn tyrosine kinase is a key pathophysiological event in human ChAc cells, we took advantage of Vps13a−/− mice, which phenocopied human ChAc. Using proteomic approach, we found accumulation of active Lyn, γ-synuclein and phospho-tau proteins in Vps13a−/− basal ganglia secondary to impaired autophagy leading to neuroinflammation. Mice double knockout Vps13a−/− Lyn−/− showed normalization of red cell morphology and improvement of autophagy in basal ganglia. We then in vivo tested pharmacologic inhibitors of Lyn: dasatinib and nilotinib. Dasatinib failed to cross the mouse brain blood barrier (BBB), but the more specific Lyn kinase inhibitor nilotinib, crosses the BBB. Nilotinib ameliorates both Vps13a−/− hematological and neurological phenotypes, improving autophagy and preventing neuroinflammation. Our data support the proposal to repurpose nilotinib as new therapeutic option for ChAc patients.
Authors: Peikert K*, Federti E*, Matte A, Constantin G, Pietronigro EC, Fabene PF, Defilippi P, Turco E, Del Gallo F, Pucci P, Amoresano A, Illiano A, Cozzolino F, Monti M, Garello F, Terreno E, Alper SL, Glaß H, Pelzl L, Akgün K, Ziemssen T, Ordemann R, Lang F, Brunati AM, Tibaldi E, Andolfo I, Iolascon A, Bertini G, Buffelli M, Zancanaro C, Lorenzetto E, Siciliano A, Bonifacio M, Danek A, Walker RH, Hermann A*, De Franceschi L*. https://doi:10.1186/s40478-021-01181-y
*contributed equally
Targeting Lyn Kinase in Chorea-Acanthocytosis: A Translational Treatment Approach in a Rare Disease
May 2021
Abstract: Chorea-acanthocytosis (ChAc) is a neurodegenerative disease caused by mutations in the VPS13A gene. It is characterized by several neurological symptoms and the appearance of acanthocytes. Elevated tyrosine kinase Lyn activity has been recently identified as one of the key pathophysiological mechanisms in this disease, and therefore represents a promising drug target. Methods: We evaluated an individual off-label treatment with the tyrosine kinase inhibitor dasatinib (100 mg/d, 25.8–50.4 weeks) of three ChAc patients. Alongside thorough safety monitoring, we assessed motor and non-motor scales (e.g., MDS-UPDRS, UHDRS, quality of life) as well as routine and experimental laboratory parameters (e.g., serum neurofilament, Lyn kinase activity, actin cytoskeleton in red blood cells). Results: Dasatinib appeared to be reasonably safe. The clinical parameters remained stable without significant improvement or deterioration. Regain of deep tendon reflexes was observed in one patient. Creatine kinase, serum neurofilament levels, and acanthocyte count did not reveal consistent effects. However, a reduction of initially elevated Lyn kinase activity and accumulated autophagy markers, as well as a partial restoration of the actin cytoskeleton, was found in red blood cells. Conclusions: We report on the first treatment approach with disease-modifying intention in ChAc. The experimental parameters indicate target engagement in red blood cells, while clinical effects on the central nervous system could not be proven within a rather short treatment time. Limited knowledge on the natural history of ChAc and the lack of appropriate biomarkers remain major barriers for “clinical trial readiness”. We suggest a panel of outcome parameters for future clinical trials in ChAc.
Authors: Peikert K, Glaß H, Federti E, Matte A, Pelzl L, Akgün K, Ziemssen T, Ordemann R, Lang F. The Network for Translational Research for Neuroacanthocytosis Patients, De Franceschi L*, Hermann A*. May 2021. Journal of Personalized Medicine 11(5):392.https://doi.org/10.3390/jpm11050392
*contributed equally
The Erythrocyte Sedimentation Rate and Its Relation to Cell Shape and Rigidity of Red Blood Cells from Chorea-Acanthocytosis Patients in an Off-Label Treatment with Dasatinib
May 2021
Abstract: Background: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified. Methods: RBCs of two ChAc patients during and after dasatinib treatment were characterized by the ESR, clinical hematology parameters and the 3D shape classification in stasis based on an artificial neural network. Furthermore, mathematical modeling was performed to understand the contribution of cell morphology and cell rigidity to the ESR. Microfluidic measurements were used to compare the RBC rigidity between ChAc patients and healthy controls. Results: The mechano-morphological characterization of RBCs from two ChAc patients in an off-label treatment with dasatinib revealed differences in the ESR and the acanthocyte count during and after the treatment period, which could not directly be related to each other. Clinical hematology parameters were in the normal range. Mathematical modeling indicated that RBC rigidity is more important for delayed ESR than cell shape. Microfluidic experiments confirmed a higher rigidity in the normocytes of ChAc patients compared to healthy controls. Conclusions: The results increase our understanding of the role of acanthocytes and their associated properties in the ESR, but the data are too sparse to answer the question of whether the ESR is a suitable biomarker for treatment success, whereas a correlation between hematological and neuronal phenotype is still subject to verification.
Authors: Rabe A*, Kihm A*, Darras A*, Peikert K*, Simionato G*, Dasanna AK*, Glaß H, Geisel J, Quint S, Danek A, Wagner C, Fedosov DA, Hermann A, Kaestner L. May 2021. Biomolecules 11(5):727. https://doi.org/10.3390/biom11050727.
*contributed equally.
Acanthocyte Sedimentation Rate as a Diagnostic Biomarker for Neuroacanthocytosis Syndromes: Experimental Evidence and Physical Justification
April 2021
Abstract: (1) Background: Chorea-acanthocytosis and McLeod syndrome are the core diseases among the group of rare neurodegenerative disorders called neuroacanthocytosis syndromes (NASs). NAS patients have a variable number of irregularly spiky erythrocytes, so-called acanthocytes. Their detection is a crucial but error-prone parameter in the diagnosis of NASs, often leading to misdiagnoses. (2) Methods: We measured the standard Westergren erythrocyte sedimentation rate (ESR) of various blood samples from NAS patients and healthy controls. Furthermore, we manipulated the ESR by swapping the erythrocytes and plasma of different individuals, as well as replacing plasma with dextran. These measurements were complemented by clinical laboratory data and single-cell adhesion force measurements. Additionally, we followed theoretical modeling approaches. (3) Results: We show that the acanthocyte sedimentation rate (ASR) with a two-hour read-out is significantly prolonged in chorea-acanthocytosis and McLeod syndrome without overlap compared to the ESR of the controls. Mechanistically, through modern colloidal physics, we show that acanthocyte aggregation and plasma fibrinogen levels slow down the sedimentation. Moreover, the inverse of ASR correlates with the number of acanthocytes (R2=0.61, p=0.004). (4) Conclusions: The ASR/ESR is a clear, robust and easily obtainable diagnostic marker. Independently of NASs, we also regard this study as a hallmark of the physical view of erythrocyte sedimentation by describing anticoagulated blood in stasis as a percolating gel, allowing the application of colloidal physics theory.
Authors: Darras A*, Peikert K*, Rabe A, Yaya F, Simionato G, John T, Dasanna AK, Buvalyy S, Geisel J, Hermann A, Fedosov DA, Danek A, Wagner C, Kaestner L. April 2021. Cells 10(4):788. https://doi.org/10.3390/cells10040788.
*contributed equally.