Stem cell therapy is being explored for several rare neurological conditions in humans given their potential immunomodulatory, reparative, and regenerative capabilities. Existing standard treatments for most neuroinflammatory and neurodegenerative disorders are primarily palliative, focusing on symptom management rather than addressing underlying disease pathology. The genetic and pathophysiological parallels between many human and animal neurological diseases suggest that companion animals may serve as valuable translational models to drive stem cell research forward. Several rare human neurological conditions with companion animal (particularly canine) correlates include fulminant multiple sclerosis (MS), myasthenia gravis, amyotrophic lateral sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Dravet and Lennox-Gastaut Syndromes, Globoid Cell Leukodystrophy/Krabbe Disease, viral encephalitis, and glioblastoma multiforme (GBM). Validating the safety and feasibility of stem cell transplantation in companion animal models has enabled the development and expansion of innovative therapies. Stem cell therapy may hold promise as a novel treatment option for some rare and aggressive human and companion animal neurological diseases with limited treatment options.

Systemic lupus erythematosus (SLE) remains a major clinical challenge due to its broad phenotypic variability, unpredictable disease trajectory, and inconsistent therapeutic responses. The limitations of conventional diagnostic and prognostic tools underscore the need for more precise, data-driven approaches to support clinical decision-making. Artificial intelligence-based methods, including machine learning (ML) have emerged as powerful technologies capable of analyzing complex, high-dimensional data to reveal hidden patterns and enhance disease understanding. These methods are particularly well-suited for tackling the multifactorial nature of SLE and have demonstrated utility in improving diagnostic accuracy, classifying disease subtypes, and guiding personalized treatment strategies. This review offers a clinician-oriented overview of foundational ML approaches and their practical applications in SLE, highlighting how these tools might be incorporated into clinical workflows to support more timely, accurate, and individualized care.

The SET nuclear proto-oncogene (SET; MIM# 600960) is a recently identified cause of autosomal dominant mental retardation-58 (MRD58), characterized by intellectual disability (ID), developmental delay, and variable additional clinical features. This report details two novel cases of MRD58 caused by de novo mutations in the SET gene (one in-frame deletion and one frameshift mutation), broadening the known phenotypic spectrum. Patient 1, a 3-year-old girl, presented with global developmental delay (GDD), seizures, right thumb polydactyly, pes planus and strabismus. Patient 2, a boy aged 1 year and 10 months, exhibited severe GDD, hypotonia, squared skull, and pes planus without seizures. Trio whole-exome sequencing identified novel likely pathogenic SET variants: c.292_294del (p.Thr98del) in Patient 1 and c.491_494del (p.Pro164LeufsTer15) in Patient 2. A review of 14 previously reported cases highlights ID and speech delay as universal features, with motor delay, facial dysmorphism, and skeletal anomalies being common; seizures appear less frequent. These cases underscore MRD58's variable expressivity and emphasize speech/language impairment as a core, persistent deficit. The report aims to enhance clinical recognition and understanding of this rare neurodevelopmental disorder.

Aim: Gaucher disease type 1 (GD1) is a lysosomal storage disorder associated with heterogeneous systemic and skeletal manifestations. Fragility fractures remain an important source of morbidity, even after initiation of enzyme replacement therapy (ERT). Validated tools to predict fracture risk in treated patients are limited.

Methods: We retrospectively analyzed 133 adult patients with GD1who were enrolled in a previously published Disease Severity Scoring System (DS3) validation study (NCT01136304). 132 ERT-treated patients were included in fracture-free survival analyses from which the one miglustat-treated patient was excluded. Baseline DS3 scores and Gaucher Risk Assessment for Fracture (GRAF) scores were calculated at treatment initiation. Fracture-free survival was assessed using Kaplan-Meier analysis, and predictive performance was evaluated using receiver operating characteristic (ROC) analysis, including combined DS3+GRAF models and Cox proportional hazards regression with age included as a continuous variable.

Results: Thirty-three patients (24.8%) experienced at least one fragility fracture during follow-up. Patients with fractures were older at treatment initiation, had longer delays between diagnosis and treatment, higher baseline DS3 and GRAF scores, and were more likely to have undergone splenectomy. For GRAF tertiles, the overall uncorrected log-rank test was significant, but Holm-corrected pairwise comparisons were not. ROC analysis showed that both the baseline DS3 score and the GRAF score moderately predicted fracture risk [area under the curve (AUC) ~0.76, 0.66 respectively]. The combined model modestly enhanced predictive performance, particularly in adults treated before age 50. The age-adjusted DS3 Cox model demonstrated a C-index of 0.80, compared with 0.78 for the age-adjusted GRAF model. Inclusion of both scores together resulted in only minimal improvement in discrimination (C-index 0.80), suggesting limited incremental predictive value of combining the two measures.

Conclusions: Pre-treatment baseline DS3 is a modestly stronger predictor of fracture risk in patients on ERT than GRAF score (Kaplan-Meier), GD1 severity itself contributes to skeletal fragility beyond the effect of aging alone (COX), and inclusion of both scores together resulted in only minimal improvement in discrimination (ROC, C-index comparison).

In clinical practice, DS3 may be preferred for baseline risk stratification, while GRAF may retain value in settings where full DS3 assessment is not feasible. Because many other fracture risk variables are not included either in DS3 or GRAF, both should be interpreted as complementary rather than stand-alone predictive tools. Reliance on dual-energy X-ray absorptiometry (DXA)-derived bone mineral density alone as a surrogate for fracture risk warrants reassessment.

The pituitary gland, though small in size, has been recognized for its essential functions since the early 20th century. Dogs played a pivotal role in understanding its endocrine function, and the history of hypophysectomy in humans and dogs is strongly interrelated. While pituitary diseases are rare in humans, they are more prevalent in dogs and cats, with neoplasia representing the most common pathology. These tumors can lead to endocrine disorders such as Cushing’s disease and acromegaly across species. The classification of diverse pituitary adenomas in humans, has prompted their investigation in veterinary patients and the advances in surgical and medical management of pituitary disease exemplify translational medicine. Techniques developed for humans, first evaluated in experimental dogs and subsequently translated into veterinary clinical practice. In the search for novel medical treatment strategies against pituitary diseases in humans, animal studies investigating the feasibility and safety of orphan drugs in large animal models like dogs and cats with spontaneous disease offer valuable information for the initiation of clinical trials in humans. While the incidence of particular pathologies differs between species, there is a common goal for all patients: refining treatment and improving outcomes. This review discusses current status and developments in treatment options for pituitary tumors in companion animals, and takes a look over the shoulder of our human counterparts to see which current, novel and future practices may be promising for our veterinary patients, and investigate how trials with orphan drugs against pituitary disease in veterinary patients can favor human clinical trials.

The feline coronavirus treatment GS-441524 represents a unique case of translational medicine in reverse: a compound developed for a rare human disease, abandoned in human clinical use, but successfully repurposed to treat a fatal veterinary condition affecting cats. Initially designed as a nucleoside analog for the Ebola virus, GS-441524 underwent preclinical safety testing in animals before being discovered to have unexpected clinical applications in feline infectious peritonitis (FIP), a historically untreatable disease in cats caused by a virulent systemic feline coronavirus (FCoV). This review traces the scientific and regulatory journey of GS-441524 from human antiviral candidate to life-saving feline treatment. We also expand the discussion to include the emerging use of other human antivirals, such as molnupiravir, in veterinary medicine. Ethical and public health tensions created by unregulated, community-driven drug access are examined, alongside the broader One Health implications, including antiviral resistance and the lack of surveillance in non-human hosts. Finally, we explore how lessons from FIP treatment may inform human medicine, particularly in the context of long COVID and future coronavirus pandemics. This translational scenario exemplifies both the potential and the pitfalls of cross-species drug translation, underscoring the need for integrated regulatory and ethical frameworks to support responsible innovation.

Aim: Familial hypercholesterolemia (FH) is a rare autosomal dominant lipid disorder, usually caused by LDLR (low-density lipoprotein receptor) mutations and strongly associated with premature coronary heart disease (CHD). Despite its clinical impact, FH remains underdiagnosed, and data on complex mutations in Asian populations are scarce. This study aimed to determine the prevalence and clinical significance of complex LDLR mutations in Taiwanese patients with heterozygous FH (HeFH), to evaluate the diagnostic utility of a two-step genetic strategy [FHChip plus MLPA (multiplex ligation-dependent probe amplification)], and to explore therapeutic implications for intensive lipid-lowering regimens and orphan drugs.

Methods: We recruited 100 index patients with phenotypic FH from National Taiwan University Hospital. Genetic testing included FHChip (Vita Genomics, Taiwan) for LDLR, apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and known InDels, followed by multiplex ligation-dependent probe amplification (MLPA) for mutation-negative cases. Complex mutations were defined as compound heterozygous, double mutations in one allele, or large LDLR rearrangements. Clinical and biochemical features were compared between patients with complex and single mutations.

Results: Pathogenic variants were detected in 76% of patients, with 12 (18.2%) harboring complex mutations. Compared with single mutations, complex mutations were associated with higher Low-density lipoprotein cholesterol (LDL-C) (319 vs. 210 mg/dL), more premature CHD (34.8% vs. 6.5%), and tendon xanthomas (69.6% vs. 1.1%). Intensive lipid-lowering therapy (statin-ezetimibe ± additional agents) achieved ~60% LDL-C reduction.

Conclusion: Complex mutations are not rare in Taiwanese HeFH and predict severe outcomes. Timely detection with FHChip-MLPA and aggressive therapy, including orphan drugs, is critical to lowering premature CHD risk in rare dyslipidemia.