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At least 19 recordsLinked to original sources
PubMed2026

InsightRP2-An Interdisciplinary Approach Toward Therapy Development in RP2-Associated Retinopathy.

Advancing the development of specific gene therapies for rare genetic eye disorders is a major challenge in modern translational vision research. It requires integrated clinical, molecular, mechanistic, and regulatory expertise, yet these aspects are often addressed in isolation. Combining complementary skills, knowledge, and expertise within an integrated, highly interactive research framework has the capacity to drive and advance therapeutic development. Moreover, early-stage involvement of patients and targeted clinical observation, alongside molecular and therapeutic research, potentially enable clinical trial readiness and support the translation of preclinical therapeutic innovations into clinical care. In this Perspective article, we present the InsightRP2 framework, an integrated translational strategy that incorporates clinical data, artificial intelligence-supported imaging analysis, experimental disease modeling, and adeno-associated virus design with the aim to facilitate the development of a targeted gene therapy for RP2-associated retinitis pigmentosa.

AAV↗
PubMed1979

Structured learning therapy: development and evaluation.

This paper describes the procedures, materials, and evaluation of Structured Learning Therapy, one of several skill training therapies to emerge in recent years. A number of issues are considered in regard to enhanced outcomes for such therapies, particularly means for more successful transfer of newly learned skills from therapy to real-life settings, and prescriptive use of such psycho-educational treatments.

Evaluation Studies as Topic↗
PubMed2026

New approaches to uncover COPD pathobiology and develop therapies.

Chronic obstructive pulmonary disease (COPD) was the third leading cause of global mortality in 2011 but receives limited attention and research funding. This Review describes the current knowledge on COPD risk factors, including genetic and epigenetic determinants and their interactions with the microbiome and environmental exposures. Preclinical models are being refined and single-cell transcriptomic, metabolomic, and proteomic technologies are being implemented to investigate the molecular mechanisms of disease progression. Patient cohorts to define biomarkers of early disease and the latest approaches to diagnose pre-COPD are essential to accelerate the development of novel and effective therapeutic interventions and translate new findings into clinical trials. This Review is a summary of topics covered by a symposium organized by the COPD-iNET consortium, an international network of researchers who have established a platform that facilitates collaboration of this multidisciplinary group of preclinical, translational, and clinical researchers.

Humans↗
PubMed2025

Screening rare genetic diagnoses for amenability to bespoke antisense oligonucleotide therapy development: A retrospective cohort study.

PURPOSE: To estimate the proportion of molecular genetic diagnoses in a real-world, phenotypically heterogeneous patient cohort that are amenable to antisense oligonucleotide (ASO) treatment. METHODS: We retrospectively applied the N=1 Collaborative's Variant Assessments toward Eligibility for Antisense Oligonucleotide Treatment guidelines to all diagnostic variants found by clinical genome-wide sequencing at a single pediatric hospital in 532 patients over a 6-year period. Variants were classified as either "eligible," "likely eligible," "unlikely eligible," or "not eligible" in relation to the different ASO approaches, or "unable to assess." RESULTS: In total, 25 unique variants across 26 patients (4.9% of 532 patients) were eligible or likely eligible for ASO treatment at a molecular genetic level, via canonical exon skipping (4), splice correction (3), or messenger RNA knockdown (19). Only 8 of these molecular genetic diagnoses were made within a year of symptom onset. After considering disease and delivery related factors, 11 diagnoses were still considered candidates for bespoke ASO development. CONCLUSION: A meaningful proportion of genetic diagnoses identified by genome-wide sequencing may be amenable to ASO treatment. These results underscore the importance of timely diagnosis, and the proactive identification and accelerated functional testing of genetic variants amenable to ASO treatments.

Humans↗
PubMed1977

[Pathology and clinical aspects of retarded child development. Diagnosis and therapy of defective development].

21 cases of "small for date" pregnancies were analysed. Serial ultrasonic tracings and determinations of total estrogen excretion in the 24-hour-urine and of serum HPL concentration were carried out. The fetal heart rate was measured by cardiotocogram. Retrospectively, the patients were divided into 3 groups according to birth weight. All patients were treated with a combination of Complamin, Calciparin and Partusisten. Fetal growth retardation could not be stopped by this treatment; there was, however, definite fetal weight gain following long term therapy. Results of HPL and total estrogen determinations were inconclusive; in most cases, however, a fall of concentrations was observed. Following long term therapy a rise in concentration up to almost normal values was seen. The positive effect of therapy was best shown by serial cardiotograms.

Betamethasone↗
PubMed1976

Developing physical therapy fee schedules based on Social Security Amendments of 1972.

Implications of the requirements related to the documentation and justification of the cost of physical therapy services are considered. These implications include 1) the cost components of physical therapy services, 2) the development of fee schedules, and 3) reimbursement requirements of third-party payers. The development of a fee schedule based on a sampling of the prevailing rates in two San Francisco Bay area counties is presented. The relationship between cost accounting, community standards, and the "prevailing rate" as defined by Medicare is documented. Public Law 92-603 and its ramifications for physical therapy fees and salaries are discussed.

California↗
PubMed1976

Plasma and erythrocyte kinetic considerations in lithium therapy.

Developments in the analysis and pharmacokinetics of lithium, and the role of the pharmacist in the management of lithium therapy in affective disorders, are described. Research showing that lithium levels in the brain may be better predicted from erythrocyte lithium levels than plasma levels is reviewed. Also reviewed is lithium kinetics in affective disorders. The pharmacist (1) determines relevant aspects of the patient's condition, (2) develops an appropriate blood sampling schedule, (3) initiates and maintains a serial lithium erythrocyte and plasma patient profile, (4) evaluates erythrocyte and serum levels in relation to established criteria to provide a basis for differential diagnosis of the patient, and (5) individualizes lithium dosage and schedules. Four cases are used to illustrate this approach. It is suggested that outpatient mental health clinics would be likely settings for the further development of this clinical role.

Adult↗
PubMed2024

AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient.

There are more than 10,000 individual rare diseases and most are without therapy. Personalized genetic therapy represents one promising approach for their treatment. We present a road map for individualized treatment of an ultra-rare disease by establishing a gene replacement therapy developed for a single patient with hereditary spastic paraplegia type 50 (SPG50). Through a multicenter collaboration, an adeno-associated virus-based gene therapy product carrying the AP4M1 gene was created and successfully administered intrathecally to a 4-year-old patient within 3 years of diagnosis as part of a single-patient phase 1 trial. Primary endpoints were safety and tolerability, and secondary endpoints evaluated efficacy. At 12 months after dosing, the therapy was well tolerated. No serious adverse events were observed, with minor events, including transient neutropenia and Clostridioides difficile gastroenteritis, experienced but resolved. Preliminary efficacy measures suggest a stabilization of the disease course. Longer follow-up is needed to confirm the safety and provide additional insights on the efficacy of the therapy. Overall, this report supports the safety of gene therapy for SPG50 and provides insights into precision therapy development for rare diseases. Clinical trial registration: NCT06069687 .

Humans↗
PubMed2025

Genetic and Demographic Determinants of Fuchs Endothelial Corneal Dystrophy Risk and Severity.

IMPORTANCE: Understanding the pathogenic mechanisms of Fuchs endothelial corneal dystrophy (FECD) could contribute to developing gene-targeted therapies. OBJECTIVE: To investigate associations between demographic data and age at first keratoplasty in a genetically refined FECD cohort. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study recruited 894 individuals with FECD at Moorfields Eye Hospital (London) and General University Hospital (Prague) from September 2009 to July 2023. Ancestry was inferred from genome-wide single nucleotide polymorphism array data. CTG18.1 status was determined by short tandem repeat and/or triplet-primed polymerase chain reaction. One or more expanded alleles (&#x2265;50 repeats) were classified as expansion-positive (Exp+). Expansion-negative (Exp-) cases were exome sequenced. MAIN OUTCOMES AND MEASURES: Association between variants in FECD-associated genes, demographic data, and age at first keratoplasty. RESULTS: Within the total cohort (n&#x2009;=&#x2009;894), 77.3% of patients were Exp+. Most European (668 of 829 [80.6%]) and South Asian (14 of 22 [63.6%]) patients were Exp+. The percentage of female patients was higher (151 [74.4%]) in the Exp- cohort compared to the Exp+ cohort (395 [57.2%]; difference, 17.2%; 95% CI, 10.1%-24.3%; P&#x2009;<&#x2009;.001). The median (IQR) age at first keratoplasty of the Exp&#x2009;+&#x2009;patients (68.2 years [63.2-73.6]) was older than the Exp- patients (61.3 years [52.6-70.4]; difference, 6.5 years; 95% CI, 3.4-9.7; P&#x2009;<&#x2009;.001). The CTG18.1 repeat length of the largest expanded allele within the Exp+ group was inversely correlated with the age at first keratoplasty (&#x3b2;, -0.087; 95% CI, -0.162 to -0.012; P&#x2009;=&#x2009;.02). The ratio of biallelic to monoallelic expanded alleles was higher in the FECD cohort (1:14) compared to an unaffected control group (1:94; P&#x2009;<&#x2009;.001), indicating that 2 Exp+ alleles were associated with increased disease penetrance compared with 1 expansion. Potentially pathogenic variants (minor allele frequency, <0.01; combined annotation dependent depletion, >15) were only identified in FECD-associated genes in 13 Exp- individuals (10.1%). CONCLUSIONS AND RELEVANCE: In this multicenter cohort study among individuals with FECD, CTG18.1 expansions were present in most European and South Asian patients, while CTG18.1 repeat length and zygosity status were associated with modifications in disease severity and penetrance. Known disease-associated genes accounted for only a minority of Exp- cases, with unknown risk factors associated with disease in the rest of this subgroup. These data may have implications for future FECD gene-targeted therapy development.

Adult↗
PubMedDate not supplied

[Studies on the development and therapy of scoliosis].

Inadequately treated cases of scoliosis with deterioration were studied. Biomechanics and pathology are discussed. It has been observed that permanent lateral deviation of the vertebral column continues irreversibly if not treated in time. A study of the evolution of scoliosis in relation to vertebral growth is reported. It is followed by a description of therapeutic management based on fundamental factors: --aetiology, the severity of the deformity, bone age and potential deterioration. A series of cases treated conservatively and by surgical fixation is illustrated.

Adolescent↗
PubMed1975

Wiskott-Aldrich syndrome with 18-year survival. Treatment with transfer factor.

An 18-year-old boy with Wiskott-Aldrich syndrome has severe symptoms of thrombocytopenia, recurrent infections, and atopic eczema. We believe he is the fifth oldest patient described with Wiskott-Aldrich syndrome. Recently, a malignant lymphoma of the histiocytic type appeared in the skin, while he was receiving transfer factor. To our knowledge, he is the only reported patient with lymphoma in the skin, but four other patients with Wiskott-Aldrich syndrome have developed malignant lymphoreticular lymphoma during transfer factor therapy. Detailed immunologic studies show failure to make a sustained antibody response to various antigens, lack of delayed hypersensitivity responsiveness, and failure of proliferative response to antigens in in vitro cultures. The IgE and IgA levels were high, and the IgM and IgG levels were low. Although clinical improvement followed transfer factor therapy, development of the malignant lymphoma was not prevented.

Adolescent↗
PubMed1979

Cimetidine-induced neutropenia: a possible dose-related phenomenon.

Neutropenia associated with high-dose cimetidine therapy developed in a patient in whom earlier therapy, as well as rechallenge with low-dose cimetidine, did not result in neutropenia. As other factors cannot be implicated, a dose-related toxicity of cimetidine appears likely. Although the mechanism of cimetidine-induced neutropenia is unknown, it may involve the previously demonstrated ability of histamine H2 receptor antagonists to block the histamine-induced initiation of DNA synthesis in bone marrow stem cells.

Adult↗
PubMed1976

Yersinia enterocolitica septicemia with septic arthritis.

We report a case of Yersinia enterocolitica septicemia with septic arthritis. Gentamicin administration controlled the septicemia but failed to eradicate the organisms in the joint, in spite of a synovial fluid level four times its minimal inhibitory concentration after four days of therapy. Development of azotemia necessitated change of antibiotic therapy to chloramphenicol, which eradicated the infection. While Y enterocolitica infection in the United States is uncommon, it must be added to the list of organisms causing suppurative arthritis and septicemia in susceptible hosts. Septic arthritis must be distinguished from the much more common reactive theumatic polyarthritis associated with Y enterocolimica infection, for which antibiotic therapy is neither needed nor helpful.

Adolescent↗